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A Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02548585
Recruitment Status : Completed
First Posted : September 14, 2015
Results First Posted : April 5, 2019
Last Update Posted : April 5, 2019
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus
Interventions Drug: MEDI0382
Drug: Placebo
Enrollment 113
Recruitment Details The study was conducted from 09 Dec 2015 to 24 Feb 2017 in Germany.
Pre-assignment Details A total of 422 participants were screened, of which 113 participants were randomized in the study.
Arm/Group Title Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg Cohort 4: MEDI0382 200 mcg Cohort 5: MEDI0382 300 mcg Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description Participants received placebo (matched to either 100 micrograms [mcg], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6). Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Period Title: Overall Study
Started 45 6 6 7 25 12 12
Treated 45 6 6 7 25 11 12
Completed 43 6 6 5 22 10 11
Not Completed 2 0 0 2 3 2 1
Reason Not Completed
Withdrawal by Subject             0             0             0             0             0             1             0
Lost to Follow-up             1             0             0             0             0             0             0
Other             1             0             0             2             3             0             1
Randomized but not treated             0             0             0             0             0             1             0
Arm/Group Title Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg Cohort 4: MEDI0382 200 mcg Cohort 5: MEDI0382 300 mcg Cohort 6: MEDI0382 300 mcg TOTAL
Hide Arm/Group Description Participants received placebo (matched to either 100 micrograms [mcg], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6). Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17). Total of all reporting groups
Overall Number of Baseline Participants 45 6 6 7 25 11 12 112
Hide Baseline Analysis Population Description
As-treated Population (ATP) included all participants who received any study drug and analyzed according to the treatment they actually received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants 6 participants 6 participants 7 participants 25 participants 11 participants 12 participants 112 participants
57.2  (6.0) 62.5  (2.9) 60.2  (4.2) 57.0  (4.9) 56.0  (7.2) 54.8  (6.8) 54.6  (6.5) 56.9  (6.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 6 participants 6 participants 7 participants 25 participants 11 participants 12 participants 112 participants
Female
18
  40.0%
1
  16.7%
4
  66.7%
2
  28.6%
12
  48.0%
4
  36.4%
3
  25.0%
44
  39.3%
Male
27
  60.0%
5
  83.3%
2
  33.3%
5
  71.4%
13
  52.0%
7
  63.6%
9
  75.0%
68
  60.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 6 participants 6 participants 7 participants 25 participants 11 participants 12 participants 112 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
45
 100.0%
6
 100.0%
6
 100.0%
7
 100.0%
25
 100.0%
11
 100.0%
12
 100.0%
112
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 6 participants 6 participants 7 participants 25 participants 11 participants 12 participants 112 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.9%
White
44
  97.8%
6
 100.0%
6
 100.0%
7
 100.0%
25
 100.0%
11
 100.0%
12
 100.0%
111
  99.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4)
Hide Description Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hours (hrs) after consumption of the standardized meal (with no additional food intake during this time).
Time Frame 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post standardized meal intake (SMI) on Baseline (Day -1) and EOT (Day 41)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.
Arm/Group Title Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg
Hide Arm/Group Description:
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Overall Number of Participants Analyzed 26 25
Mean (Standard Deviation)
Unit of Measure: Percent change
-9.24  (12.30) -33.81  (18.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4: Placebo, Cohort 4: MEDI0382 200 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method ANCOVA
Comments p-value was based on pairwise comparison using analysis of covariance (ANCOVA) adjusted by baseline value.
2.Primary Outcome
Title Change From Baseline in Body Weight to the EOT (Cohort 4)
Hide Description [Not Specified]
Time Frame Baseline (Day 1) and EOT (Day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized and received any study drug and analyzed according to the initial randomization.
Arm/Group Title Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg
Hide Arm/Group Description:
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Overall Number of Participants Analyzed 26 25
Mean (Standard Deviation)
Unit of Measure: Kilograms (Kg)
-1.71  (2.10) -3.83  (2.09)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 4: Placebo, Cohort 4: MEDI0382 200 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method ANCOVA
Comments p-value was based on pairwise comparison using ANCOVA adjusted by baseline value.
3.Secondary Outcome
Title Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6)
Hide Description Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time Frame 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Hide Outcome Measure Data
Hide Analysis Population Description
PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 5 11 5 12
Mean (Standard Deviation)
Unit of Measure: Percent change
-14.60  (5.56) -41.80  (11.07) -15.07  (13.46) -36.73  (10.09) -0.47  (15.16) -39.58  (5.27) -14.52  (8.12) -41.66  (9.97) -4.80  (3.45) -38.19  (12.51)
4.Secondary Outcome
Title Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6)
Hide Description [Not Specified]
Time Frame Cohort 1: Baseline (Day 1) to EOT (Day 8); Cohort 2: Baseline (Day 1) to EOT (Day 12); Cohort 3: Baseline (Day 1) to EOT (Day 16); Cohort 5: Baseline (Day 1) to EOT (Day 22); Cohort 6: Baseline (Day 1) to EOT (Day 17)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized and received any study drug and analyzed according to the initial randomization. Participants who did not complete the treatment were not included in this analysis.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 5 11 5 12
Mean (Standard Deviation)
Unit of Measure: Kg
-1.20  (0.44) -2.32  (1.29) -1.00  (1.13) -1.52  (0.57) -2.90  (1.05) -4.63  (1.98) -0.98  (2.12) -3.26  (1.99) -0.94  (3.09) -2.04  (1.52)
5.Secondary Outcome
Title Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6)
Hide Description [Not Specified]
Time Frame Cohort 4: Baseline (Day -2) to EOT (Day 42); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized and received any study drug and analyzed according to the initial randomization. Participants who did not complete the treatment were not included in this analysis.
Arm/Group Title Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 26 25 5 11 5 12
Mean (Standard Deviation)
Unit of Measure: Percent change
-0.58  (0.30) -0.92  (0.41) -0.10  (0.29) -0.55  (0.35) -0.18  (0.19) -0.42  (0.27)
6.Secondary Outcome
Title Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6)
Hide Description [Not Specified]
Time Frame Cohort 4: Baseline (Day -2) to EOT (Day 41); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized and received any study drug and analyzed according to the initial randomization. Participants who did not complete the treatment were not included in this analysis.
Arm/Group Title Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 26 25 5 11 5 12
Mean (Standard Deviation)
Unit of Measure: micromol/L
-33.7  (44.6) -67.9  (44.4) -27.8  (25.8) -47.4  (15.7) -48.8  (43.7) -47.5  (55.3)
7.Secondary Outcome
Title Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time Frame Cohort 1: Baseline (Day-1) to EOT (Day7); Cohort 2: Baseline (Day-1) to EOT (Day11); Cohort 3: Baseline (Day-1) to EOT (Day15); Cohort 4: Baseline (Day-1) to EOT (Day41); Cohort 5: Baseline (Day-1) to EOT (Day22); Cohort 6: Baseline (Day-1) to EOT (Day17)
Hide Outcome Measure Data
Hide Analysis Population Description
PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25 5 11 5 12
Mean (Standard Deviation)
Unit of Measure: mg/dL
-32.44  (17.19) -74.48  (24.59) -49.86  (23.24) -54.06  (19.51) -4.20  (33.73) -63.67  (11.93) -18.52  (18.88) -50.62  (33.61) -32.08  (17.49) -54.42  (19.75) -16.58  (12.45) -55.21  (31.13)
8.Secondary Outcome
Title Percent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time Frame 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, 240 minutes, and 24 hrs post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Hide Outcome Measure Data
Hide Analysis Population Description
PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25 5 11 5 12
Mean (Standard Deviation)
Unit of Measure: Percent change
-21.80  (1.41) -28.34  (13.52) 0.80  (39.55) -29.32  (17.24) -13.80  (15.95) -27.07  (10.82) -1.06  (11.47) -13.50  (18.19) -4.20  (28.58) -34.51  (11.25) -10.10  (14.69) -26.95  (9.45)
9.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Hide Description An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse events (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days).
Time Frame From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
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Hide Analysis Population Description
As-treated Population (ATP) included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25 5 11 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
2
  66.7%
6
 100.0%
3
 100.0%
5
  83.3%
3
 100.0%
7
 100.0%
23
  88.5%
22
  88.0%
4
  80.0%
10
  90.9%
2
  40.0%
10
  83.3%
TESAEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
1
   3.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
10.Secondary Outcome
Title Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs
Hide Description TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to vital signs and physical examination abnormalities were reported.
Time Frame From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25 5 11 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Blood Pressure increased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   7.7%
1
   4.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Blood pressure systolic increased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   9.1%
1
  20.0%
0
   0.0%
Blood pressure diastolic increased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
Physical Examinations
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
11.Secondary Outcome
Title Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs
Hide Description TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to ECG abnormalities were reported.
Time Frame From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25 5 11 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Arrhythmia
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Atrial fibrillation
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Atrioventricular block first degree
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Atrioventricular block second degree
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Electrocardiogram ST segment depression
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Extrasystoles
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sinus tachycardia
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Supraventricular extrasystoles
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Supraventricular tachycardia
1
  33.3%
1
  16.7%
1
  33.3%
0
   0.0%
1
  33.3%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Tachycardia
0
   0.0%
1
  16.7%
0
   0.0%
1
  16.7%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ventricular extrasystoles
0
   0.0%
1
  16.7%
1
  33.3%
1
  16.7%
0
   0.0%
0
   0.0%
1
   3.8%
1
   4.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ventricular tachycardia
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs
Hide Description TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to laboratory abnormalities were reported.
Time Frame From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Hide Outcome Measure Data
Hide Analysis Population Description
ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25 5 11 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Lipase increased
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
2
  18.2%
0
   0.0%
1
   8.3%
Hypokalemia
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.8%
1
   4.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
C-reactive protein increased
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Hypoglycemia
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Chromaturia
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
1
   9.1%
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6)
Hide Description The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal ideation were reported below.
Time Frame Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 26 25 5 11 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Day -1 Number Analyzed 26 participants 25 participants 5 participants 11 participants 5 participants 12 participants
1
   3.8%
4
  16.0%
0
   0.0%
2
  18.2%
0
   0.0%
2
  16.7%
Day 13 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
1
   3.8%
0
   0.0%
Day 20 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
0
   0.0%
0
   0.0%
Day 27 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
0
   0.0%
0
   0.0%
Day 34 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
0
   0.0%
0
   0.0%
Day 40 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
0
   0.0%
0
   0.0%
Days 7-14 post last dose of MEDI0382 Number Analyzed 0 participants 0 participants 5 participants 11 participants 5 participants 12 participants
0
   0.0%
1
   9.1%
0
   0.0%
0
   0.0%
14.Secondary Outcome
Title Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6)
Hide Description The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal behaviour were reported below.
Time Frame Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)
Hide Outcome Measure Data
Hide Analysis Population Description
ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 26 25 5 11 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
Day -1 Number Analyzed 26 participants 25 participants 5 participants 11 participants 5 participants 12 participants
2
   7.7%
2
   8.0%
0
   0.0%
1
   9.1%
0
   0.0%
1
   8.3%
Day 13 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
1
   3.8%
0
   0.0%
Day 20 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
0
   0.0%
0
   0.0%
Day 27 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
0
   0.0%
0
   0.0%
Day 34 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
0
   0.0%
0
   0.0%
Day 40 Number Analyzed 26 participants 25 participants 0 participants 0 participants 0 participants 0 participants
0
   0.0%
0
   0.0%
Days 7-14 post last dose of MEDI0382 Number Analyzed 0 participants 0 participants 5 participants 11 participants 5 participants 12 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
15.Secondary Outcome
Title Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3)
Hide Description Terminal elimination half Life is the time measured for the plasma concentration of MEDI0382 to decrease by one half.
Time Frame Cohort (C) 1 (Day [D] 1 and [&] D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.
Arm/Group Title Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg
Hide Arm/Group Description:
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Overall Number of Participants Analyzed 6 6 7
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr
Day 1 Number Analyzed 1 participants 0 participants 0 participants
8.5 [1] 
(NA to NA)
Day 5 Number Analyzed 0 participants 2 participants 0 participants
10.3
(7.8 to 13.5)
Day 7 Number Analyzed 3 participants 0 participants 0 participants
11.7
(5.5 to 25.1)
Day 9 Number Analyzed 0 participants 0 participants 1 participants
8.3 [2] 
(NA to NA)
Day 11 Number Analyzed 0 participants 6 participants 0 participants
11.3
(5.9 to 21.7)
Day 15 Number Analyzed 0 participants 0 participants 5 participants
11.3
(8.2 to 15.5)
[1]
95% confidence interval (CI) was not reported as only one participant was evaluable for the specified time point.
[2]
95% CI was not reported as only one participant was evaluable for the specified time point.
16.Secondary Outcome
Title Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3)
Hide Description Accumulation ratio was calculated as, Rac obtained from area under the curve from time zero to end of dosing interval (AUC[0-tau]) of Nth day divided by AUC(0-tau) of Day 1.
Time Frame C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.
Arm/Group Title Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg
Hide Arm/Group Description:
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Overall Number of Participants Analyzed 6 6 7
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
Day 1 Number Analyzed 6 participants 0 participants 0 participants
NA [1] 
(NA to NA)
Day 5 Number Analyzed 0 participants 6 participants 0 participants
NA [2] 
(NA to NA)
Day 7 Number Analyzed 6 participants 0 participants 0 participants
1.3
(1.1 to 1.5)
Day 9 Number Analyzed 0 participants 0 participants 6 participants
NA [3] 
(NA to NA)
Day 11 Number Analyzed 0 participants 6 participants 0 participants
1.1
(0.9 to 1.8)
Day 15 Number Analyzed 0 participants 0 participants 5 participants
1.3
(1.1 to 1.5)
[1]
Data is not applicable since accumulation ratio, as described by the formula could not be derived for Cohort 1 Day 1.
[2]
Data is not applicable since accumulation ratio, as described by the formula could not be derived for Cohort 2 Day 5.
[3]
Data is not applicable since accumulation ratio, as described by the formula could not be derived for Cohort 3 Day 9.
17.Secondary Outcome
Title Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description [Not Specified]
Time Frame C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.
Arm/Group Title Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg Cohort 4: MEDI0382 200 mcg Cohort 5: MEDI0382 300 mcg Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 6 6 7 25 11 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng*hr/mL
Day 1 Number Analyzed 6 participants 0 participants 0 participants 0 participants 0 participants 0 participants
82.21
(44.56 to 151.69)
Day 5 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 0 participants
174.58
(87.41 to 348.67)
Day 7 Number Analyzed 6 participants 0 participants 0 participants 0 participants 0 participants 0 participants
107.01
(54.10 to 211.64)
Day 9 Number Analyzed 0 participants 0 participants 4 participants 23 participants 0 participants 0 participants
194.78
(146.17 to 259.56)
164.05
(42.67 to 630.76)
Day 11 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 11 participants
157.31
(82.45 to 421.12)
275.29
(169.33 to 447.48)
Day 15 Number Analyzed 0 participants 0 participants 5 participants 0 participants 0 participants 0 participants
195.40
(89.8 to 425.17)
Day 16 Number Analyzed 0 participants 0 participants 0 participants 0 participants 11 participants 0 participants
261.90
(166.58 to 411.74)
Day 17 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 11 participants
246.06
(130.34 to 464.51)
Day 22 Number Analyzed 0 participants 0 participants 0 participants 0 participants 10 participants 0 participants
254.35
(196.10 to 329.9)
Day 41 Number Analyzed 0 participants 0 participants 0 participants 22 participants 0 participants 0 participants
199.10
(84.57 to 468.75)
18.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description [Not Specified]
Time Frame C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.
Arm/Group Title Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg Cohort 4: MEDI0382 200 mcg Cohort 5: MEDI0382 300 mcg Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 6 6 7 25 11 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng*hr/mL
Day 1 Number Analyzed 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants
103.46 [1] 
(NA to NA)
Day 5 Number Analyzed 0 participants 2 participants 0 participants 0 participants 0 participants 0 participants
207.15
(11.98 to 3580.41)
Day 7 Number Analyzed 3 participants 0 participants 0 participants 0 participants 0 participants 0 participants
184.68
(107.76 to 316.51)
Day 9 Number Analyzed 0 participants 0 participants 1 participants 13 participants 0 participants 0 participants
242.60 [1] 
(NA to NA)
238.22
(80.99 to 700.67)
Day 11 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 0 participants
215.80
(112.90 to 412.47)
Day 15 Number Analyzed 0 participants 0 participants 5 participants 0 participants 0 participants 0 participants
271.84
(119.33 to 619.24)
Day 16 Number Analyzed 0 participants 0 participants 0 participants 0 participants 6 participants 0 participants
317.93
(182.24 to 554.64)
Day 17 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 4 participants
327.28
(249.98 to 428.49)
Day 22 Number Analyzed 0 participants 0 participants 0 participants 0 participants 4 participants 0 participants
294.60
(172.52 to 503.05)
Day 41 Number Analyzed 0 participants 0 participants 0 participants 11 participants 0 participants 0 participants
262.17
(99.79 to 688.77)
[1]
95% CI data not applicable as only one participant was evaluable for this time point.
19.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description [Not Specified]
Time Frame C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.
Arm/Group Title Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg Cohort 4: MEDI0382 200 mcg Cohort 5: MEDI0382 300 mcg Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 6 6 7 25 11 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
Day 1 Number Analyzed 6 participants 0 participants 0 participants 0 participants 0 participants 0 participants
4.97
(0.33 to 7.41)
Day 5 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 0 participants
9.66
(4.68 to 19.95)
Day 7 Number Analyzed 6 participants 0 participants 0 participants 0 participants 0 participants 0 participants
6.26
(3.36 to 11.67)
Day 9 Number Analyzed 0 participants 0 participants 6 participants 23 participants 0 participants 0 participants
10.57
(6.33 to 17.66)
11.64
(3.16 to 42.94)
Day 11 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 11 participants
9.57
(4.63 to 19.79)
13.69
(5.73 to 32.71)
Day 15 Number Analyzed 0 participants 0 participants 5 participants 0 participants 0 participants 0 participants
10.97
(4.62 to 26.06)
Day 16 Number Analyzed 0 participants 0 participants 0 participants 0 participants 11 participants 0 participants
17.65
(8.82 to 35.29)
Day 17 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 11 participants
15.55
(7.55 to 32.01)
Day 22 Number Analyzed 0 participants 0 participants 0 participants 0 participants 10 participants 0 participants
15.77
(10.02 to 24.8)
Day 41 Number Analyzed 0 participants 0 participants 0 participants 22 participants 0 participants 0 participants
13.42
(4.77 to 37.75)
20.Secondary Outcome
Title Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description [Not Specified]
Time Frame C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.
Arm/Group Title Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg Cohort 4: MEDI0382 200 mcg Cohort 5: MEDI0382 300 mcg Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 6 6 7 25 11 12
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
Day 1 Number Analyzed 6 participants 0 participants 0 participants 0 participants 0 participants 0 participants
0.705
(0.33 to 1.49)
Day 5 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 0 participants
2.685
(1.06 to 6.79)
Day 7 Number Analyzed 6 participants 0 participants 0 participants 0 participants 0 participants 0 participants
2.372
(1.18 to 4.78)
Day 9 Number Analyzed 0 participants 0 participants 6 participants 23 participants 0 participants 0 participants
3.521
(2.16 to 5.75)
2.635
(0.79 to 8.83)
Day 11 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 11 participants
3.59
(1.62 to 7.94)
3.586
(1.45 to 8.88)
Day 15 Number Analyzed 0 participants 0 participants 5 participants 0 participants 0 participants 0 participants
4.973
(2.24 to 11.05)
Day 16 Number Analyzed 0 participants 0 participants 0 participants 0 participants 11 participants 0 participants
4.062
(1.68 to 9.84)
Day 17 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 11 participants
4.766
(2.74 to 8.3)
Day 22 Number Analyzed 0 participants 0 participants 0 participants 0 participants 10 participants 0 participants
5.21
(1.97 to 13.81)
Day 41 Number Analyzed 0 participants 0 participants 0 participants 22 participants 0 participants 0 participants
3.38
(1.03 to 11.04)
21.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description [Not Specified]
Time Frame C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK population included all participants who received at least 1 dose of study drug and had at least one PK sample taken that was above the lower limit of quantitation.
Arm/Group Title Cohort 1: MEDI0382 100 mcg Cohort 2: MEDI0382 150 mcg Cohort 3: MEDI0382 200 mcg Cohort 4: MEDI0382 200 mcg Cohort 5: MEDI0382 300 mcg Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 6 6 7 25 11 12
Median (Full Range)
Unit of Measure: hr
Day 1 Number Analyzed 6 participants 0 participants 0 participants 0 participants 0 participants 0 participants
8
(6 to 8)
Day 5 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 0 participants
6
(4 to 8)
Day 7 Number Analyzed 6 participants 0 participants 0 participants 0 participants 0 participants 0 participants
6
(4 to 6)
Day 9 Number Analyzed 0 participants 0 participants 6 participants 23 participants 0 participants 0 participants
6
(6 to 8)
4
(1 to 6)
Day 11 Number Analyzed 0 participants 6 participants 0 participants 0 participants 0 participants 11 participants
6
(4 to 6)
6
(4 to 12)
Day 15 Number Analyzed 0 participants 0 participants 5 participants 0 participants 0 participants 0 participants
6
(4 to 8)
Day 16 Number Analyzed 0 participants 0 participants 0 participants 0 participants 11 participants 0 participants
4
(2 to 8)
Day 17 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 11 participants
4
(2 to 6)
Day 22 Number Analyzed 0 participants 0 participants 0 participants 0 participants 10 participants 0 participants
4
(4 to 8)
Day 41 Number Analyzed 0 participants 0 participants 0 participants 22 participants 0 participants 0 participants
4
(4 to 8)
22.Secondary Outcome
Title Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description [Not Specified]
Time Frame Day 1 up to 7-14 days post-last dose of MEDI0382 for all cohorts (Approximately 60 days)
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Hide Analysis Population Description
ATP included all participants who received any study drug and analyzed according to the treatment they actually received.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25 5 11 5 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
23.Secondary Outcome
Title Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6)
Hide Description Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time Frame 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Hide Outcome Measure Data
Hide Analysis Population Description
PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17).
Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25 5 11 5 12
Mean (Standard Deviation)
Unit of Measure: Percent change
10.83  (21.33) -9.37  (29.17) -3.67  (13.76) 36.32  (35.21) -20.43  (68.82) -17.47  (38.84) -8.63  (32.33) -1.17  (44.20) -17.70  (16.47) 1.01  (31.00) -8.18  (28.34) -7.72  (37.03)
24.Secondary Outcome
Title Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Hide Description Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time Frame 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)
Hide Outcome Measure Data
Hide Analysis Population Description
PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25
Mean (Standard Deviation)
Unit of Measure: Percent change
-3.27  (38.92) -52.10  (36.29) -33.13  (40.07) -36.77  (19.62) 81.27  (77.21) -54.13  (26.40) -29.72  (31.13) -47.93  (22.12)
25.Secondary Outcome
Title Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Hide Description Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time Frame 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)
Hide Outcome Measure Data
Hide Analysis Population Description
PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25
Mean (Standard Deviation)
Unit of Measure: Percent change
10.17  (5.05) -3.82  (21.29) -1.43  (6.02) 39.78  (32.88) 79.37  (91.56) -9.07  (27.27) 8.08  (32.12) 15.66  (42.35)
26.Secondary Outcome
Title Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Hide Description Mixes-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). Incretins included glucagon-like peptide-1 (GLP-1; active and inactive both), glucagon, and gastric inhibitory peptide (GIP).
Time Frame 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)
Hide Outcome Measure Data
Hide Analysis Population Description
PD population included all participants who received at least 1 dose of study drug and had at least 1 post-MMT PD blood sample.
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg
Hide Arm/Group Description:
Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7.
Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41).
Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Overall Number of Participants Analyzed 3 6 3 6 3 7 26 25
Mean (Standard Deviation)
Unit of Measure: Percent change
GLP-1, Active: Change at EOT Number Analyzed 2 participants 6 participants 3 participants 6 participants 3 participants 5 participants 24 participants 19 participants
8.30  (13.15) -33.67  (16.84) -10.40  (10.47) -50.45  (12.30) -2.87  (20.32) -40.36  (26.90) 1.63  (26.43) -49.73  (22.88)
GLP-1, Inactive: Change at EOT Number Analyzed 1 participants 1 participants 1 participants 3 participants 2 participants 3 participants 14 participants 8 participants
-20.30 [1]   (NA) 0.70 [2]   (NA) -22.90 [2]   (NA) -10.93  (22.36) 1.75  (29.20) -8.07  (11.30) 3.99  (29.59) -28.85  (16.73)
Glucagon: Change at EOT Number Analyzed 2 participants 4 participants 3 participants 5 participants 3 participants 2 participants 18 participants 12 participants
-13.85  (18.60) -20.25  (25.45) -17.53  (19.46) -38.12  (16.33) -18.73  (21.59) -3.05  (36.56) -1.76  (21.47) -30.17  (25.56)
GIP: Change at EOT Number Analyzed 2 participants 2 participants 2 participants 5 participants 2 participants 5 participants 17 participants 12 participants
18.00  (2.83) -46.50  (14.85) 4.10  (24.61) -27.08  (25.03) -6.30  (7.35) -21.34  (39.48) -6.60  (19.43) -37.38  (23.14)
[1]
Standard deviation (SD) data not applicable as only one participant was evaluable for the specified parameter.
[2]
SD data not applicable as only one participant was evaluable for the specified parameter.
Time Frame From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Hide Arm/Group Description Participants received placebo matched to (MEDI0382 100 mcg) SC once daily from Day 1 to Day 7. Participants received MEDI0382 100 mcg SC once daily from Day 1 to Day 7. Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 7 days (Day 5 to Day 11). Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11). Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 7 days (Day 9 to Day 15). Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15). ) Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 4 days (Day 9 to Day 12), then a further placebo (matched to MEDI0382 200 mcg) SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by placebo (matched to MEDI0382 200 mcg) SC once daily for 1 day in hospital (Day 41). Participants received MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41). Participants received placebo (matched to MEDI0382 100 mcg ) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 150 mcg) SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 16 to Day 22). Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22). Participants received placebo (matched to MEDI0382 100 mcg) SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of placebo (matched to MEDI0382 200 mcg) SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of placebo (matched to MEDI0382 300 mcg) SC once daily for 7 days (Day 11 to Day 17). Participants received MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
All-Cause Mortality
Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/3 (0.00%)      0/6 (0.00%)      0/3 (0.00%)      0/6 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/26 (0.00%)      0/25 (0.00%)      0/5 (0.00%)      0/11 (0.00%)      0/5 (0.00%)      0/12 (0.00%)    
Hide Serious Adverse Events
Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/6 (0.00%)      0/3 (0.00%)      0/6 (0.00%)      0/3 (0.00%)      1/7 (14.29%)      1/26 (3.85%)      0/25 (0.00%)      0/5 (0.00%)      0/11 (0.00%)      0/5 (0.00%)      0/12 (0.00%)    
Eye disorders                         
Diplopia † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Infections and infestations                         
Pneumonia mycoplasmal † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA 19.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1: Placebo Cohort 1: MEDI0382 100 mcg Cohort 2: Placebo Cohort 2: MEDI0382 150 mcg Cohort 3: Placebo Cohort 3: MEDI0382 200 mcg Cohort 4: Placebo Cohort 4: MEDI0382 200 mcg Cohort 5: Placebo Cohort 5: MEDI0382 300 mcg Cohort 6: Placebo Cohort 6: MEDI0382 300 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/3 (66.67%)      6/6 (100.00%)      3/3 (100.00%)      5/6 (83.33%)      3/3 (100.00%)      7/7 (100.00%)      23/26 (88.46%)      22/25 (88.00%)      4/5 (80.00%)      10/11 (90.91%)      2/5 (40.00%)      10/12 (83.33%)    
Cardiac disorders                         
Angina pectoris † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 1/25 (4.00%)  1 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Atrial fibrillation † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 1/25 (4.00%)  1 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Atrioventricular block first degree † 1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Atrioventricular block second degree † 1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Extrasystoles † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  2 0/6 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Palpitations † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 1/25 (4.00%)  1 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Sinus tachycardia † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 1/25 (4.00%)  1 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Supraventricular extrasystoles † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Supraventricular tachycardia † 1  1/3 (33.33%)  7 1/6 (16.67%)  1 1/3 (33.33%)  1 1/6 (16.67%)  1 1/3 (33.33%)  1 1/7 (14.29%)  1 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Tachycardia † 1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0 1/7 (14.29%)  1 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Ventricular extrasystoles † 1  0/3 (0.00%)  0 1/6 (16.67%)  1 1/3 (33.33%)  1 1/6 (16.67%)  3 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 1/25 (4.00%)  1 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Ventricular tachycardia † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1 1/7 (14.29%)  1 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Arrhythmia † 1  0/3 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Ear and labyrinth disorders                         
Vertigo positional † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 1/25 (4.00%)  1 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Eye disorders                         
Abnormal sensation in eye † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Vision blurred † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 2/7 (28.57%)  2 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 1/12 (8.33%)  1
Visual acuity reduced † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal disorders                         
Abdominal discomfort † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 3/25 (12.00%)  3 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Abdominal distension † 1  0/3 (0.00%)  0 3/6 (50.00%)  3 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/26 (0.00%)  0 6/25 (24.00%)  9 0/5 (0.00%)  0 2/11 (18.18%)  2 0/5 (0.00%)  0 0/12 (0.00%)  0
Abdominal pain † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 2/7 (28.57%)  2 1/26 (3.85%)  1 1/25 (4.00%)  4 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Abdominal pain lower † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Abdominal pain upper † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 1/25 (4.00%)  1 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 1/12 (8.33%)  1
Constipation † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 2/6 (33.33%)  2 0/3 (0.00%)  0 1/7 (14.29%)  1 3/26 (11.54%)  5 6/25 (24.00%)  7 1/5 (20.00%)  1 0/11 (0.00%)  0 0/5 (0.00%)  0 1/12 (8.33%)  1
Diarrhoea † 1  1/3 (33.33%)  1 0/6 (0.00%)  0 1/3 (33.33%)  1 0/6 (0.00%)  0 1/3 (33.33%)  8 1/7 (14.29%)  2 3/26 (11.54%)  4 4/25 (16.00%)  6 1/5 (20.00%)  1 1/11 (9.09%)  2 0/5 (0.00%)  0 2/12 (16.67%)  2
Dry mouth † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 1/12 (8.33%)  1
Dyspepsia † 1  0/3 (0.00%)  0 1/6 (16.67%)  2 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 3/7 (42.86%)  3 1/26 (3.85%)  1 7/25 (28.00%)  7 0/5 (0.00%)  0 4/11 (36.36%)  7 0/5 (0.00%)  0 2/12 (16.67%)  2
Eructation † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/6 (16.67%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 4/25 (16.00%)  4 0/5 (0.00%)  0 3/11 (27.27%)  3 0/5 (0.00%)  0 0/12 (0.00%)  0
Faeces discoloured † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 2/11 (18.18%)  2 0/5 (0.00%)  0 0/12 (0.00%)  0
Faeces hard † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 1/12 (8.33%)  1
Faeces soft † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 2/26 (7.69%)  3 2/25 (8.00%)  2 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Flatulence † 1  1/3 (33.33%)  1 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Gastrooesophageal reflux disease † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 1/11 (9.09%)  1 0/5 (0.00%)  0 0/12 (0.00%)  0
Infrequent bowel movements † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 1/11 (9.09%)  1 0/5 (0.00%)  0 0/12 (0.00%)  0
Intra-abdominal haematoma † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 1/5 (20.00%)  1 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Nausea † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 3/6 (50.00%)  7 0/3 (0.00%)  0 3/7 (42.86%)  4 5/26 (19.23%)  7 13/25 (52.00%)  39 1/5 (20.00%)  2 3/11 (27.27%)  6 0/5 (0.00%)  0 5/12 (41.67%)  7
Pancreatolithiasis † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0
Regurgitation † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 1/11 (9.09%)  1 0/5 (0.00%)  0 0/12 (0.00%)  0
Salivary hypersecretion † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 0/25 (0.00%)  0 0/5 (0.00%)  0 1/11 (9.09%)  1 0/5 (0.00%)  0 0/12 (0.00%)  0
Vomiting † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 2/6 (33.33%)  2 0/3 (0.00%)  0 3/7 (42.86%)  8 0/26 (0.00%)  0 8/25 (32.00%)  40 0/5 (0.00%)  0 3/11 (27.27%)  9 0/5 (0.00%)  0 1/12 (8.33%)  2
General disorders                         
Asthenia † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/26 (0.00%)  0 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 1/12 (8.33%)  2
Early satiety † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 0/25 (0.00%)  0 0/5 (0.00%)  0 2/11 (18.18%)  2 0/5 (0.00%)  0 0/12 (0.00%)  0
Fatigue † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/26 (0.00%)  0 5/25 (20.00%)  5 0/5 (0.00%)  0 2/11 (18.18%)  2 0/5 (0.00%)  0 0/12 (0.00%)  0
Feeling hot † 1  0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/26 (3.85%)  1 0/25 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/5 (0.00%)  0 0/12 (0.00%)  0