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To Assess the Safety, Tolerability and Pharmacokinetics of AZD5634 Following Inhaled and Intravenous (IV)Dose Administration

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: NCT02679729
Recruitment Status : Completed
First Posted : February 10, 2016
Results First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Investigator);   Primary Purpose: Basic Science
Condition Cystic Fibrosis
Interventions Drug: AZD5634 for inhalation
Drug: AZD5634 for infusion
Other: Placebo
Enrollment 63
Recruitment Details Phase 1, first-in-human (FIH), single-blind, placebo-controlled, single ascending dose (SAD), sequential dose group study in healthy male participants and female participants of non-childbearing potential at 2 study centers (EPCU Baltimore and EPCU Los Angeles). The study comprised of Part A and Part B.
Pre-assignment Details The study consisted of a screening period (Days -28 to -1).
Arm/Group Title Part A - AZD5634 - 10 μg Part A - AZD5634 27 μg Part A - AZD5634 81 μg Part A - AZD5634 216 μg Part A - AZD5634 648 μg Part A - AZD5634 1296 μg Part A - AZD5634 1692 μg Part A - Placebo PartB- AZD5634-Intravenous(IV) 65μg and Inhalation(IN) 1692μg
Hide Arm/Group Description Participants received inhaled single doses of AZD5634 10 μg under fasted conditions Participants received inhaled single doses of AZD5634 27 μg under fasted conditions Participants received inhaled single doses of AZD5634 81 μg under fasted conditions Participants received inhaled single doses of AZD5634 216 μg under fasted conditions Participants received inhaled single doses of AZD5634 648 μg under fasted conditions Participants received inhaled single doses of AZD5634 1296 μg under fasted conditions Participants received inhaled single doses of AZD5634 1692 μg under fasted conditions 2 participants per dose level received single dose of placebo in Part A After safety evaluation of all inhaled AZD5634 cohorts, 6 participants (who did not participate in Part A) were admitted for inhaled (1692 μg AZD5634) and IV (65 μg AZD5634) dosing (fixed dosing; IV first followed by inhalation), with at least a 14 day washout between dosing
Period Title: Overall Study
Started 6 7 6 6 6 6 6 14 6
Completed 6 5 6 6 5 6 5 14 6
Not Completed 0 2 0 0 1 0 1 0 0
Reason Not Completed
Lost to Follow-up             0             1             0             0             1             0             0             0             0
Participant decision             0             1             0             0             0             0             1             0             0
Arm/Group Title AZD5634 - Inhaled 10 μg AZD5634 27 μg AZD5634 81 μg AZD5634 216 μg AZD5634 648 μg AZD5634 1296 μg AZD5634 1692 μg Placebo AZD5634 - IV 65 μg and IN 1692 μg Total
Hide Arm/Group Description Participants received inhaled single doses of AZD5634 10 μg under fasted conditions Participants received inhaled single doses of AZD5634 27 μg under fasted conditions Participants received inhaled single doses of AZD5634 81 μg under fasted conditions Participants received inhaled single doses of AZD5634 216 μg under fasted conditions Participants received inhaled single doses of AZD5634 648 μg under fasted conditions Participants received inhaled single doses of AZD5634 1296 μg under fasted conditions Participants received inhaled single doses of AZD5634 1692 μg under fasted conditions 2 participants per dose level received single dose of placebo in Part A After safety evaluation of all inhaled AZD5634 cohorts, 6 participants (who did not participate in Part A) were admitted for inhaled (1692 μg AZD5634) and IV (65 μg AZD5634) dosing (fixed dosing; IV first followed by inhalation), with at least a 14 day washout between dosing Total of all reporting groups
Overall Number of Baseline Participants 6 7 6 6 6 6 6 14 6 63
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Part A Number Analyzed 6 participants 7 participants 6 participants 6 participants 6 participants 6 participants 6 participants 14 participants 0 participants 57 participants
36.5  (12.2) 33.3  (9.3) 31.8  (3.4) 32.0  (6.9) 37.7  (9.1) 31.7  (5.2) 35.2  (10.6) 32.6  (8.9) 34.0  (8.3)
Part B Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 6 participants 6 participants
32.0  (7.9) 32.0  (7.9)
[1]
Measure Analysis Population Description: Data for Part A and Part B are presented in separate rows. Part A and Part B data when added (57 + 6) will give the overall total of 63
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 7 participants 6 participants 6 participants 6 participants 6 participants 6 participants 14 participants 6 participants 63 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
  16.7%
1
   7.1%
0
   0.0%
3
   4.8%
Male
6
 100.0%
7
 100.0%
6
 100.0%
6
 100.0%
5
  83.3%
6
 100.0%
5
  83.3%
13
  92.9%
6
 100.0%
60
  95.2%
1.Primary Outcome
Title Safety and Tolerability of AZD5634 Following Inhaled Administration of Single-ascending Doses (SAD) (Part A) and Following Administration of Single Inhaled and IV Doses (Part B).
Hide Description To assess the safety and tolerability of AZD5634 in terms of number of participants following inhaled administration of single-ascending doses (SAD) (Part A) and following administration of single inhaled and IV doses (Part B)
Time Frame Screening (serious adverse event, SAE), Day -1 (SAE), Spontaneous plus Predose, 3,12,24, and 48 h postdose (Days 1 to 3), Follow-up 7-10 days postdose, 2 months post final dose.
Hide Outcome Measure Data
Hide Analysis Population Description
All partcipants in safety analysis set who received at least 1 dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
Arm/Group Title Part A - AZD5634 10 µg Part A - AZD5634 27 µg Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part A - Placebo for AZD5634 Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 10 µg under fasted conditions
Participants received inhaled single doses of AZD5634 27 µg under fasted conditions
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
2 participants per dose level received single dose of placebo in Part A
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 6 7 6 6 6 6 6 14 6 6
Measure Type: Number
Unit of Measure: Participants
Any AE during treatment 1 0 0 1 1 0 2 3 2 1
Any AE with outcome = death 0 0 0 0 0 0 0 0 0 0
Any SAE (including events with outcome = death) 0 0 0 0 0 0 0 0 0 0
Any AE during Follow-up 1 0 0 0 0 0 0 0 0 0
2.Secondary Outcome
Title Observed Maximum Plasma Concentration, Taken Directly From the Individual Concentration-time Curve (Cmax)- For Part A and Part B
Hide Description To assess the pharmacokinetic (PK) parameter Cmax of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
0.01605
(18.8%)
0.04581
(45.2%)
0.2977
(20.0%)
0.3043
(46.5%)
0.5316
(51.6%)
6.070
(8.9%)
0.3808
(34.7%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A - AZD5634 81 µg, Part A - AZD5634 216 µg, Part A - AZD5634 648 µg, Part A - AZD5634 1296 µg, Part A - AZD5634 1692 µg
Comments Statistical Analysis for Part A
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 0.625
Confidence Interval (2-Sided) 95%
0.396 to 0.853
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Area Under Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part A and Part B
Hide Description To assess the pharmacokinetic parameter AUC of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. AUC was estimated by AUC(0-last) + Clast/λz where Clast was the last observed quantifiable concentration. AUCs were calculated using the linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. AUC0-t is expanded as area under the plasma concentration-time curve from time zero to time of last quantifiable concentration. Note:Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*nmol/L
NA [1] 
(NA%)
0.1757
(34.9%)
1.258
(16.7%)
1.299
(57.2%)
2.837
(71.5%)
2.329
(11.3%)
1.777
(37.2%)
[1]
Due to the participant and/or data exclusion, data were not available
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A - AZD5634 81 µg, Part A - AZD5634 216 µg, Part A - AZD5634 648 µg, Part A - AZD5634 1296 µg, Part A - AZD5634 1692 µg
Comments Statistical Analysis for Part A
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.905 to 1.49
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-t)] for Part A and Part B
Hide Description To assess the pharmacokinetic parameter AUC(0-t) of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*nmol/L
0.01920
(60.1%)
0.1120
(62.2%)
1.301
(22.0%)
1.244
(57.2%)
2.664
(60.9%)
2.318
(11.4%)
1.831
(38.0%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part A - AZD5634 81 µg, Part A - AZD5634 216 µg, Part A - AZD5634 648 µg, Part A - AZD5634 1296 µg, Part A - AZD5634 1692 µg
Comments Statistical Analysis for Part A
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
1.34 to 1.76
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Absolute Systemic Bioavailability After Inhalation (Part B Only) (Finhalation,Total)
Hide Description To assess the Absolute systemic bioavailability after inhalation (%), calculated separately as 100*AUCinhalation*Doseiv/(AUCiv*Doseinhalation)
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part B consisted of all participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated in each treatment period, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Percentage of bioavailable dose
NA [1] 
(NA%)
2.928
(42.2%)
[1]
Due to the participant and/or data exclusion, data were not available
6.Secondary Outcome
Title Renal Clearance (CLR), Estimated by Dividing Ae(0-last) by AUC0-t - For Part A and Part B
Hide Description To assess the pharmacokinetic parameter CLR of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame -12-0, 0-6, 6-12, 12-24, 24-48 h (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: L/h
1.449  (0.1332) 0.8099  (0.2849) 0.5828  (0.1724) 0.9063  (0.2459) 0.7333  (0.1893) 0.6247  (0.3373) 0.6939  (0.1044)
7.Secondary Outcome
Title Cmax, Divided by the Dose Aministered (Cmax/Dose) - For Part A and Part B
Hide Description To assess the pharmacokinetic parameter Cmax/Dose of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L/umol
0.1473
(18.8%)
0.1576
(45.2%)
0.3415
(20.0%)
0.1745
(46.5%)
0.2335
(51.6%)
69.41
(8.9%)
0.1673
(34.7%)
8.Secondary Outcome
Title Terminal Half-life (t1/2λz), Estimated as (ln2)/λz - For Part A and Part B
Hide Description To assess the pharmacokinetic parameter t1/2λz of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: Hours
NA [1]   (NA) 1.519  (0.1499) 1.903  (0.4722) 3.144  (2.250) 7.552  (5.438) 0.1923  (0.05567) 3.184  (1.816)
[1]
Due to the participant and/or data exclusion, data were not available
9.Secondary Outcome
Title AUC0-t, Divided by the Dose Administered (AUC0-t/Dose) - For Part A and Part B
Hide Description To assess the pharmacokinetic parameter AUC0-t/Dose of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*nmol/L/umol
0.1762
(60.1%)
0.3856
(62.2%)
1.492
(22.0%)
0.7137
(57.2%)
1.170
(60.9%)
26.51
(11.4%)
0.8044
(38.0%)
10.Secondary Outcome
Title AUC, Divided by the Dose Administered (AUC/Dose) - For Part A and Part B
Hide Description To assess the pharmacokinetic parameter AUC/Dose of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*nmol/L/umol
NA [1] 
(NA%)
0.6046
(34.9%)
1.444
(16.7%)
0.7450
(57.2%)
1.246
(71.5%)
26.63
(11.3%)
0.7805
(37.2%)
[1]
Due to the participant and/or data exclusion, data were not available
11.Secondary Outcome
Title Systemic Clearance for AZD5634 Estimated as Dose Divided by AUC (Part B IV Dosing Only) (CL)
Hide Description To assess the pharmacokinetic parameter CL of AZD5634 following single-dose IV administration of AZD5634 in Part B
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part B consisted of all participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated in each treatment period, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part B - AZD5634 IV 65 µg
Hide Arm/Group Description:
Participants received IV dose of AZD5634 65 µg
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: L/h
37.74  (4.220)
12.Secondary Outcome
Title Apparent Clearance for AZD5634 Estimated as Dose Divided by AUC (Part A and Part B Inhaled Dosing Only) (CL/F)
Hide Description To assess the pharmacokinetic parameter CL/F of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6
Mean (Standard Deviation)
Unit of Measure: L/h
NA [1]   (NA) 1727  (589.7) 699.9  (115.3) 1518  (852.7) 929.8  (548.2) 1346  (457.8)
[1]
Due to the participant and/or data exclusion, data were not available
13.Secondary Outcome
Title Mean Residence Time (MRT) - For Part A and Part B
Hide Description To assess the pharmacokinetic parameter MRT of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and following single-dose IV or inhalation administration of AZD5634 in Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: hour
NA [1]   (NA) 2.742  (0.1741) 3.529  (0.5093) 4.157  (1.166) 6.000  (2.009) 0.1928  (0.02455) 4.428  (1.293)
[1]
Due to the participant and/or data exclusion, data were not available
14.Secondary Outcome
Title Mean Absorption Time, Calculated as MRTinhaled - MRTIV (Part B Only) (MAT)
Hide Description To assess the pharmacokinetic parameter MAT of AZD5634 following single-dose IV or inhalation administration of AZD5634 in Part B
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part B consisted of all participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated in each treatment period, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received IV dose of AZD5634 65 µg
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 6 6
Mean (Standard Deviation)
Unit of Measure: hour
NA [1]   (NA) 4.236  (1.302)
[1]
This parameter analysis was not applicable for this arm.
15.Secondary Outcome
Title Volume of Distribution for AZD5634 at Steady State (IV Administration), Estimated by Dividing the MRT by the Systemic CL (Part B IV Dosing Only) (Vss)
Hide Description To assess the pharmacokinetic parameter Vss of AZD5634 following single-dose IV administration of AZD5634 in Part B
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part B consisted of all participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated in each treatment period, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part B - AZD5634 IV 65 µg
Hide Arm/Group Description:
Participants received IV dose of AZD5634 65 µg
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: Litre
7.202  (0.3915)
16.Secondary Outcome
Title Volume of Distribution for AZD5634 at Terminal Phase (IV Administration), Estimated by Dividing the Systemic CL by λz (Part B IV Dosing Only) (Vz)
Hide Description To assess the pharmacokinetic parameter Vz of AZD5634 following single-dose IV administration of AZD5634 in Part B
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part B consisted of all participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated in each treatment period, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part B - AZD5634 IV 65 µg
Hide Arm/Group Description:
Participants received IV dose of AZD5634 65 µg
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: Litre
10.25  (1.804)
17.Secondary Outcome
Title Apparent Volume of Distribution for AZD5634 at Terminal Phase (Inhaled Administration), Estimated by Dividing the CL/F by λz (Part A and Part B Inhaled Dosing Only) (Vz/F)
Hide Description To assess the pharmacokinetic parameter Vz/F of AZD5634 following single-dose inhalation administration of AZD5634 in Part A and Part B. Note: Due to the participant and/or data exclusion described above, there are no PK data available for the 10 μg dose cohort and very limited data for the 27 μg dose cohort. Therefore, these 2 cohorts were not included in PK results interpretation and summary statistics.
Time Frame At predose, at 5, 15 and 30 min and at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 h postdose (Days 1 to 3)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set for Part A consisted of participants in the safety analysis set who received AZD5634 and for Part B consisted of participants who completed both treatment periods and for whom at least one of the PK parameters Cmax, AUC0-t or AUC were calculated, with no major protocol deviations thought to impact on the analysis of the PK data.
Arm/Group Title Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description:
Participants received inhaled single doses of AZD5634 81 µg under fasted conditions
Participants received inhaled single doses of AZD5634 216 µg under fasted conditions
Participants received inhaled single doses of AZD5634 648 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions
Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions
Participants received an IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
Overall Number of Participants Analyzed 3 5 5 6 5 6
Mean (Standard Deviation)
Unit of Measure: Litre
NA [1]   (NA) 3775  (1306) 1864  (178.2) 5416  (1905) 7115  (2202) 5361  (1077)
[1]
Due to the participant and/or data exclusion, data were not available
Time Frame Screening (SAE), Day -1 (SAE), Spontaneous plus Predose, 3,12,24, and 48 h postdose (Days 1 to 3), Follow-up 7-10 days postdose, 2 months post final dose.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part A - AZD5634 10 µg Part A - AZD5634 27 µg Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part A - Placebo for AZD5634 Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
Hide Arm/Group Description Participants received inhaled single doses of AZD5634 10 µg under fasted conditions Participants received inhaled single doses of AZD5634 27 µg under fasted conditions Participants received inhaled single doses of AZD5634 81 µg under fasted conditions Participants received inhaled single doses of AZD5634 216 µg under fasted conditions Participants received inhaled single doses of AZD5634 648 µg under fasted conditions Participants received inhaled single doses of AZD5634 1296 µg under fasted conditions Participants received inhaled single doses of AZD5634 1692 µg under fasted conditions 2 participants per dose level received single dose of placebo in Part A Participants received IV dose of IV 65 µg Participants received IV dose and after a washout period of 14 days this was followed by an inhaled dose AZD5634 1692 µg to the same participants
All-Cause Mortality
Part A - AZD5634 10 µg Part A - AZD5634 27 µg Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part A - Placebo for AZD5634 Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
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   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Part A - AZD5634 10 µg Part A - AZD5634 27 µg Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part A - Placebo for AZD5634 Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
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   0/6 (0.00%)   0/7 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/14 (0.00%)   0/6 (0.00%)   0/6 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Part A - AZD5634 10 µg Part A - AZD5634 27 µg Part A - AZD5634 81 µg Part A - AZD5634 216 µg Part A - AZD5634 648 µg Part A - AZD5634 1296 µg Part A - AZD5634 1692 µg Part A - Placebo for AZD5634 Part B - AZD5634 IV 65 µg Part B - AZD5634 IN 1692 µg
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   1/6 (16.67%)   0/7 (0.00%)   0/6 (0.00%)   1/6 (16.67%)   1/6 (16.67%)   0/6 (0.00%)   2/6 (33.33%)   3/14 (21.43%)   2/6 (33.33%)   1/6 (16.67%) 
Cardiac disorders                     
Atrioventricular block second degree * 1  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Ear and labyrinth disorders                     
Ear pain * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders                     
Nausea * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Vomiting * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
General disorders                     
Medical device site dermatitis * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/14 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Infections and infestations                     
Paronychia * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/6 (0.00%) 
Viral upper respiratory tract infection * 1  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications                     
Laceration * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/6 (0.00%) 
Skin abrasion * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders                     
Muscle twitching * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Nervous system disorders                     
Headache * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/6 (0.00%) 
Dizziness * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/14 (7.14%)  0/6 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders                     
Dyspnoea * 1  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/14 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 19.0.
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.
All clinical study findings and documents will be regarded as confidential and property of the sponsor. No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Leader
Organization: AstraZeneca AB
Phone: +46 766 346712
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02679729    
Other Study ID Numbers: D6600C00001
First Submitted: February 3, 2016
First Posted: February 10, 2016
Results First Submitted: August 11, 2017
Results First Posted: November 5, 2018
Last Update Posted: November 5, 2018