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Comparison of Pharmacokinetics of Infacort® Versus Immediate-release Hydrocortisone

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ClinicalTrials.gov Identifier: NCT02777268
Recruitment Status : Completed
First Posted : May 19, 2016
Results First Posted : August 10, 2017
Last Update Posted : December 2, 2017
Sponsor:
Collaborator:
Simbec Research
Information provided by (Responsible Party):
Diurnal Limited

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Healthy Subjects
Interventions Drug: Infacort
Drug: Hydrocortisone
Enrollment 16
Recruitment Details Recruitment Area: United Kingdom Location: Phase 1 Unit
Pre-assignment Details  
Arm/Group Title All Study Participants
Hide Arm/Group Description

5-way crossover study design involving Infacort and hydrocortisone at the following dose strengths:

Infacort 0.5mg Infacort 2mg Infacort 5mg Infacort 10mg Hydrocortisone 10mg

Each IMP was administered to each subject in a randomised, crossover manner over 5 treatment periods (1 treatment/period). During each treatment period, each subject was admitted to the Unit on the afternoon of Day 1 and remained in the Unit until completion of all scheduled assessments on Day 2. Each subject received their scheduled IMP on the morning of Day 2 at ~0700hrs (fasted). Each subject also received 1mg dexamethasone (to suppress endogenous cortisol production) at approximately 2200hrs on Day 1, and at approximately 0600hrs and 1200hrs on Day 2. All doses were administered with 200mL water. There were at least 7 days washout between each dose of IMP.

Period Title: Overall Study
Started 16
Completed 16
Not Completed 0
Arm/Group Title All Study Participants
Hide Arm/Group Description

5-way crossover study design involving Infacort and hydrocortisone at the following dose strengths:

Infacort 0.5mg Infacort 2mg Infacort 5mg Infacort 10mg Hydrocortisone 10mg

Each IMP was administered to each subject in a randomised, crossover manner over 5 treatment periods (1 treatment/period). During each treatment period, each subject was admitted to the Unit on the afternoon of Day 1 and remained in the Unit until completion of all scheduled assessments on Day 2. Each subject received their scheduled IMP on the morning of Day 2 at ~0700hrs (fasted). Each subject also received 1mg dexamethasone (to suppress endogenous cortisol production) at approximately 2200hrs on Day 1, and at approximately 0600hrs and 1200hrs on Day 2. All doses were administered with 200mL water. There were at least 7 days washout between each dose of IMP.

Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
<=18 years
0
   0.0%
Between 18 and 65 years
16
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
40.70  (14.370)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
0
   0.0%
Male
16
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   6.3%
White
15
  93.8%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
United Kingdom Number Analyzed 16 participants
16
[1]
Measure Description: United Kingdom
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 16 participants
25.34  (2.085)
Height (m)  
Mean (Standard Deviation)
Unit of measure:  Metres (m)
Number Analyzed 16 participants
1.773  (0.081)
Weight (kg)  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 16 participants
79.70  (8.543)
Medical History and Concurrent Conditions  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
0
   0.0%
Drug/Alcohol and HIV/Hepatitis Screening  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
0
   0.0%
1.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Infacort vs Hydrocortisone
Hide Description To compare the Cmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg.
Time Frame -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
Hide Outcome Measure Data
Hide Analysis Population Description
Two subjects were excluded from the Infacort 10mg analysis population due to inadequate endogenous cortisol suppression prior to dosing.
Arm/Group Title Infacort 10mg Hydrocortisone
Hide Arm/Group Description:
Multi-particulate granules from 10mg Infacort capsule

1 (10 mg) tablet

Hydrocortisone: Tablet

Overall Number of Participants Analyzed 14 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
601.843
(21.5%)
622.384
(15.8%)
2.Primary Outcome
Title Time to Reach the Maximum Plasma Concentration (Tmax) of Infacort vs Hydrocortisone
Hide Description To compare the Tmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg.
Time Frame -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
Hide Outcome Measure Data
Hide Analysis Population Description
Two subjects were excluded from the Infacort 10mg analysis population due to inadequate endogenous cortisol suppression prior to dosing.
Arm/Group Title Infacort 10mg Hydrocortisone
Hide Arm/Group Description:
Multi-particulate granules from a 10mg Infacort capsule.
10 mg hydrocortisone tablet
Overall Number of Participants Analyzed 14 14
Median (Standard Deviation)
Unit of Measure: Hour
0.500  (0.4031) 1  (0.4171)
3.Primary Outcome
Title Area Under the Curve (AUC0-t) of Infacort vs Hydrocortisone
Hide Description To compare the AUC0-t of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg. AUC0-t represents the total exposure to drug over time, hence the reporting of a single value below.
Time Frame -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
Hide Outcome Measure Data
Hide Analysis Population Description
Two subjects were excluded from the Infacort 10mg analysis population due to inadequate endogenous cortisol suppression prior to dosing.
Arm/Group Title Infacort 10 mg Hydrocortisone
Hide Arm/Group Description:
Multi-particulate granules from 1 Infacort 10 mg capsule
1 (10 mg) hydrocortisone tablet
Overall Number of Participants Analyzed 14 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*nmol/L
1836.718
(17.8%)
1803.278
(14.6%)
4.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg
Hide Description To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg.
Time Frame -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Infacort 0.5mg Infacort 2mg Infacort 5mg Infacort 10mg
Hide Arm/Group Description:

Multi-particulate granules from 1 (0.5 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (2mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (5mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (10mg) capsule

Infacort: Multi-particulate granules

Overall Number of Participants Analyzed 15 15 15 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
92.220
(22.9%)
242.798
(16.0%)
424.310
(14.8%)
601.843
(21.5%)
5.Secondary Outcome
Title Time to Maximum Plasma Concentration (Tmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg
Hide Description To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg.
Time Frame -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Infacort 0.5 mg Infacort 2 mg Infacort 5 mg Infacort 10 mg
Hide Arm/Group Description:

Multi-particulate granules from 1 (0.5 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (2 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (5 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (10 mg) capsule

Infacort: Multi-particulate granules

Overall Number of Participants Analyzed 15 15 15 14
Median (Standard Deviation)
Unit of Measure: Hours
0.500  (0.2236) 0.500  (0.3010) 0.500  (0.3162) 0.500  (0.4031)
6.Secondary Outcome
Title Area Under the Curve (AUC0-t) of Infacort at Doses of 0.5, 2, 5 and 10 mg
Hide Description To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg.
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Infacort 0.5 mg Infacort 2 mg Infacort 5 mg Infacort 10 mg
Hide Arm/Group Description:

Multi-particulate granules from 1 (0.5 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (2 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (5 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (10 mg) capsule

Infacort: Multi-particulate granules

Overall Number of Participants Analyzed 14 14 14 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: H*nmol/L
326.129
(21.3%)
648.407
(16.6%)
1127.579
(15.2%)
1836.718
(17.8%)
7.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Assessed by Medical Dictionary for Regulatory Activities (MedDRA) Dictionary, Version 16.0.
Hide Description To assess the safety and tolerability of Infacort® throughout the study. For a full list of TEAEs per arm, please refer to the Adverse Events section.
Time Frame 1 day
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Study Participants
Hide Arm/Group Description:

5-way crossover study design involving Infacort and hydrocortisone at the following dose strengths:

Infacort 0.5mg Infacort 2mg Infacort 5mg Infacort 10mg Hydrocortisone 10mg

Each IMP was administered to each subject in a randomised, crossover manner over 5 treatment periods (1 treatment/period). During each treatment period, each subject was admitted to the Unit on the afternoon of Day 1 and remained in the Unit until completion of all scheduled assessments on Day 2. Each subject received their scheduled IMP on the morning of Day 2 at ~0700hrs (fasted). Each subject also received 1mg dexamethasone (to suppress endogenous cortisol production) at approximately 2200hrs on Day 1, and at approximately 0600hrs and 1200hrs on Day 2. All doses were administered with 200mL water. There were at least 7 days washout between each dose of IMP.

Overall Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: TEAEs
7
Time Frame From study start (19 July 2013) to completion (9 September 2013)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Infacort 0.5 mg Infacort 2 mg Infacort 5 mg Infacort 10 mg Hydrocortisone
Hide Arm/Group Description

Multi-particulate granules from 1 (0.5 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (2 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (5 mg) capsule

Infacort: Multi-particulate granules

Multi-particulate granules from 1 (10 mg) capsule

Infacort: Multi-particulate granules

1 (10 mg) tablet

Hydrocortisone: Tablet

All-Cause Mortality
Infacort 0.5 mg Infacort 2 mg Infacort 5 mg Infacort 10 mg Hydrocortisone
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Infacort 0.5 mg Infacort 2 mg Infacort 5 mg Infacort 10 mg Hydrocortisone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/16 (0.00%)      0/16 (0.00%)      0/16 (0.00%)      0/16 (0.00%)      0/16 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Infacort 0.5 mg Infacort 2 mg Infacort 5 mg Infacort 10 mg Hydrocortisone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/16 (6.25%)      1/16 (6.25%)      0/16 (0.00%)      4/16 (25.00%)      1/16 (6.25%)    
Gastrointestinal disorders           
Nausea * 1  1/16 (6.25%)  1 0/16 (0.00%)  0 0/16 (0.00%)  0 0/16 (0.00%)  0 0/16 (0.00%)  0
Abdominal pain * 1  0/16 (0.00%)  0 0/16 (0.00%)  0 0/16 (0.00%)  0 1/16 (6.25%)  1 0/16 (0.00%)  0
Hypoaesthesia oral * 1  0/16 (0.00%)  0 0/16 (0.00%)  0 0/16 (0.00%)  0 2/16 (12.50%)  2 0/16 (0.00%)  0
Nervous system disorders           
Dysgeusia * 1  0/16 (0.00%)  0 1/16 (6.25%)  1 0/16 (0.00%)  0 0/16 (0.00%)  0 0/16 (0.00%)  0
Headache * 1  0/16 (0.00%)  0 0/16 (0.00%)  0 0/16 (0.00%)  0 1/16 (6.25%)  1 0/16 (0.00%)  0
Vascular disorders           
Flushing * 1  0/16 (0.00%)  0 0/16 (0.00%)  0 0/16 (0.00%)  0 0/16 (0.00%)  0 1/16 (6.25%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator must obtain written consent from the Sponsor prior to any publication of results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Girish Sharma
Organization: Simbec Research Limited
Phone: +44 1443 690977
Layout table for additonal information
Responsible Party: Diurnal Limited
ClinicalTrials.gov Identifier: NCT02777268     History of Changes
Other Study ID Numbers: Infacort 001
First Submitted: April 27, 2016
First Posted: May 19, 2016
Results First Submitted: February 9, 2017
Results First Posted: August 10, 2017
Last Update Posted: December 2, 2017