Trial Outcomes & Findings for A Study to Assess the Effect of Verinurad on the Electric Activity of the Heart (NCT NCT04256629)
NCT ID: NCT04256629
Last Updated: 2022-01-31
Results Overview
Assessment of the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of International Council for Harmonisation Guideline E14 and associated Questions and Answers \[ICH E14 Q\&A\]), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF analysis. A linear mixed-effect concentration-QTcF model was used as the primary analysis. This is a result of the statistical model so it does not have values for every timepoint, it is just one set of numbers - summarizes data across all timepoints. No non-placebo-corrected QTcF data values were collected or could be obtained for each Arm/Group at Cmax of Verinurad.
COMPLETED
PHASE1
24 participants
Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose
2022-01-31
Participant Flow
This study was conducted in 24 healthy male and female participants at a single study center - Parexel Early Phase Clinical Unit (Berlin).
The study consisted of a Screening Period of maximum 28 days. There were wash-out periods of at least 7 days between each study dose administration. The assessments were done as per the schedule of assessment.
Participant milestones
| Measure |
Treatment Sequence ABC
Randomised participants received single doses of all 3 study treatments (Treatment A: Verinurad 24 mg extended release \[ER8\] formulation co-administered with 300 mg allopurinol, Treatment B: Verinurad 40 mg immediate release \[IR\] formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence BCA
Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence CAB
Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence ACB
Randomised participants received single doses of all 3 study treatments ( Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence BAC
Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence CBA
Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
4
|
4
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
3
|
4
|
4
|
4
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Treatment Sequence ABC
Randomised participants received single doses of all 3 study treatments (Treatment A: Verinurad 24 mg extended release \[ER8\] formulation co-administered with 300 mg allopurinol, Treatment B: Verinurad 40 mg immediate release \[IR\] formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence BCA
Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence CAB
Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence ACB
Randomised participants received single doses of all 3 study treatments ( Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence BAC
Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence CBA
Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Study to Assess the Effect of Verinurad on the Electric Activity of the Heart
Baseline characteristics by cohort
| Measure |
Treatment Sequence ABC
n=4 Participants
Randomised participants received single doses of all 3 study treatments (Treatment A: Verinurad 24 mg extended release \[ER8\] formulation co-administered with 300 mg allopurinol, Treatment B: Verinurad 40 mg immediate release \[IR\] formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence BCA
n=4 Participants
Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence CAB
n=4 Participants
Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence ACB
n=4 Participants
Randomised participants received single doses of all 3 study treatments ( Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, Treatment C: Matching placebos for both verinurad and allopurinol, and Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence BAC
n=4 Participants
Randomised participants received single doses of all 3 study treatments (Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol, and Treatment C: Matching placebos for both verinurad and allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Treatment Sequence CBA
n=4 Participants
Randomised participants received single doses of all 3 study treatments (Treatment C: Matching placebos for both verinurad and allopurinol, Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol, and Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol) in a cross-over design with wash-out periods of at least 7 days between each study dose administration under fasted conditions.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
38.8 Years
STANDARD_DEVIATION 13.35 • n=5 Participants
|
30.0 Years
STANDARD_DEVIATION 6.16 • n=7 Participants
|
32.8 Years
STANDARD_DEVIATION 14.08 • n=5 Participants
|
35.5 Years
STANDARD_DEVIATION 7.14 • n=4 Participants
|
31.0 Years
STANDARD_DEVIATION 12.25 • n=21 Participants
|
34.0 Years
STANDARD_DEVIATION 12.36 • n=8 Participants
|
33.7 Years
STANDARD_DEVIATION 10.44 • n=8 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
19 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
22 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: In the Primary Outcome we present the predicted value of ΔΔQTcF based on a statistical model created for the study. The results may be presented for the active arms only, since the placebo arm did not receive Verinurad and thus have no Cmax. Placebo-corrected and baseline adjusted QTcF, ∆∆QTcF with 90% confidence interval at the verinurad maximum concentration of interest is presented as the primary result from the analysis.
Assessment of the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of International Council for Harmonisation Guideline E14 and associated Questions and Answers \[ICH E14 Q\&A\]), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF analysis. A linear mixed-effect concentration-QTcF model was used as the primary analysis. This is a result of the statistical model so it does not have values for every timepoint, it is just one set of numbers - summarizes data across all timepoints. No non-placebo-corrected QTcF data values were collected or could be obtained for each Arm/Group at Cmax of Verinurad.
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Model Predicted Baseline-corrected and Placebo-corrected QT Interval Corrected for Heart Rate (HR) Using Fridericia's Formula (QTcF)(ΔΔQTcF) (Derived From Concentration-QTcF Analysis) at Geometric Mean of Cmax of Verinurad
|
-2.8 msec
Interval -4.7 to -0.9
|
-0.3 msec
Interval -3.1 to 2.5
|
—
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hour (h) post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on heart rate (HR).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
n=24 Participants
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 1 h
|
-0.9 Beats per minute (bpm)
Interval -2.0 to 0.3
|
-1.0 Beats per minute (bpm)
Interval -2.2 to 0.1
|
0.1 Beats per minute (bpm)
Interval -1.4 to 1.6
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 1.5 h
|
-2.3 Beats per minute (bpm)
Interval -3.8 to -0.7
|
-1.3 Beats per minute (bpm)
Interval -2.5 to -0.2
|
-0.6 Beats per minute (bpm)
Interval -1.9 to 0.8
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 2 h
|
-1.9 Beats per minute (bpm)
Interval -3.5 to -0.3
|
-2.5 Beats per minute (bpm)
Interval -4.0 to -1.0
|
-0.5 Beats per minute (bpm)
Interval -1.9 to 1.0
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 3 h
|
-0.8 Beats per minute (bpm)
Interval -2.8 to 1.2
|
-1.7 Beats per minute (bpm)
Interval -3.3 to -0.1
|
0.6 Beats per minute (bpm)
Interval -0.9 to 2.1
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 4 h
|
9.3 Beats per minute (bpm)
Interval 6.2 to 12.4
|
7.2 Beats per minute (bpm)
Interval 4.9 to 9.4
|
8.7 Beats per minute (bpm)
Interval 6.2 to 11.2
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 5 h
|
6.4 Beats per minute (bpm)
Interval 3.9 to 8.8
|
5.8 Beats per minute (bpm)
Interval 3.0 to 8.5
|
6.2 Beats per minute (bpm)
Interval 4.0 to 8.4
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 6 h
|
2.8 Beats per minute (bpm)
Interval 0.6 to 4.9
|
2.3 Beats per minute (bpm)
Interval 0.3 to 4.4
|
4.1 Beats per minute (bpm)
Interval 2.4 to 5.7
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 8 h
|
9.6 Beats per minute (bpm)
Interval 8.0 to 11.3
|
6.5 Beats per minute (bpm)
Interval 4.6 to 8.3
|
8.5 Beats per minute (bpm)
Interval 6.4 to 10.6
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 12 h
|
0.3 Beats per minute (bpm)
Interval -1.4 to 1.9
|
0.8 Beats per minute (bpm)
Interval -0.7 to 2.4
|
2.3 Beats per minute (bpm)
Interval 0.2 to 4.4
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 2/ 24 h
|
0.0 Beats per minute (bpm)
Interval -1.9 to 1.9
|
1.4 Beats per minute (bpm)
Interval -0.2 to 3.0
|
0.9 Beats per minute (bpm)
Interval -1.0 to 2.8
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 2/ 36 h
|
9.1 Beats per minute (bpm)
Interval 5.5 to 12.8
|
9.6 Beats per minute (bpm)
Interval 7.0 to 12.3
|
9.5 Beats per minute (bpm)
Interval 6.0 to 13.0
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 3/ 48 h
|
4.9 Beats per minute (bpm)
Interval 2.0 to 7.8
|
3.9 Beats per minute (bpm)
Interval 2.0 to 5.8
|
5.3 Beats per minute (bpm)
Interval 3.2 to 7.3
|
|
Baseline-corrected Heart Rate (ΔHR)
Day 1/ 0.5 h
|
-0.8 Beats per minute (bpm)
Interval -1.7 to 0.1
|
-2.0 Beats per minute (bpm)
Interval -3.2 to -0.7
|
-0.5 Beats per minute (bpm)
Interval -1.8 to 0.8
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on HR.
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 0.5 h
|
-0.4 bpm
Interval -2.0 to 1.2
|
-1.4 bpm
Interval -3.2 to 0.4
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 1 h
|
-0.9 bpm
Interval -2.8 to 1.0
|
-1.1 bpm
Interval -3.0 to 0.7
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 1.5 h
|
-1.6 bpm
Interval -3.5 to 0.3
|
-0.7 bpm
Interval -2.7 to 1.3
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 2 h
|
-1.3 bpm
Interval -3.1 to 0.6
|
-1.8 bpm
Interval -3.9 to 0.2
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 3 h
|
-1.5 bpm
Interval -3.1 to 0.1
|
-2.2 bpm
Interval -4.2 to -0.2
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 4 h
|
0.5 bpm
Interval -1.7 to 2.6
|
-1.4 bpm
Interval -3.6 to 0.8
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 5 h
|
0.1 bpm
Interval -2.7 to 3.0
|
-0.3 bpm
Interval -3.7 to 3.0
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 6 h
|
-1.2 bpm
Interval -3.4 to 0.9
|
-1.6 bpm
Interval -3.9 to 0.7
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 8 h
|
1.0 bpm
Interval -1.3 to 3.3
|
-2.0 bpm
Interval -5.0 to 1.1
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 1/ 12 h
|
-2.1 bpm
Interval -4.6 to 0.4
|
-1.4 bpm
Interval -4.1 to 1.3
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 2/ 24 h
|
-0.9 bpm
Interval -2.2 to 0.5
|
0.7 bpm
Interval -1.6 to 3.0
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 2/ 36 h
|
-0.5 bpm
Interval -3.0 to 2.0
|
0.5 bpm
Interval -2.4 to 3.4
|
—
|
|
Baseline-corrected and Placebo-adjusted Heart Rate (ΔΔHR)
Day 3/ 48 h
|
-0.4 bpm
Interval -2.6 to 1.9
|
-1.1 bpm
Interval -3.8 to 1.5
|
—
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (RR).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
n=24 Participants
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 0.5 h
|
13.6 Milli second (msec)
Interval -2.1 to 29.3
|
28.2 Milli second (msec)
Interval 9.2 to 47.2
|
6.7 Milli second (msec)
Interval -17.3 to 30.7
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 1 h
|
14.8 Milli second (msec)
Interval -8.8 to 38.5
|
15.8 Milli second (msec)
Interval -4.8 to 36.3
|
-8.3 Milli second (msec)
Interval -35.6 to 19.1
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 1.5 h
|
47.1 Milli second (msec)
Interval 15.1 to 79.2
|
20.3 Milli second (msec)
Interval 5.3 to 35.3
|
6.4 Milli second (msec)
Interval -17.7 to 30.4
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 2 h
|
35.6 Milli second (msec)
Interval 7.7 to 63.6
|
36.5 Milli second (msec)
Interval 14.5 to 58.4
|
6.9 Milli second (msec)
Interval -15.6 to 29.4
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 3 h
|
11.3 Milli second (msec)
Interval -24.8 to 47.5
|
24.4 Milli second (msec)
Interval 0.2 to 48.7
|
-12.2 Milli second (msec)
Interval -37.7 to 13.2
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 4 h
|
-139.7 Milli second (msec)
Interval -194.9 to -84.5
|
-111.7 Milli second (msec)
Interval -151.7 to -71.7
|
-133.8 Milli second (msec)
Interval -181.1 to -86.5
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 5 h
|
-98.8 Milli second (msec)
Interval -145.5 to -52.1
|
-82.6 Milli second (msec)
Interval -122.6 to -42.6
|
-101.9 Milli second (msec)
Interval -143.3 to -60.5
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 6 h
|
-45.4 Milli second (msec)
Interval -83.0 to -7.8
|
-44.6 Milli second (msec)
Interval -76.8 to -12.3
|
-66.7 Milli second (msec)
Interval -96.7 to -36.7
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 8 h
|
-143.9 Milli second (msec)
Interval -173.4 to -114.4
|
-100.6 Milli second (msec)
Interval -129.8 to -71.4
|
-128.7 Milli second (msec)
Interval -165.1 to -92.4
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 1/ 12 h
|
-5.0 Milli second (msec)
Interval -39.8 to 29.7
|
-16.3 Milli second (msec)
Interval -43.1 to 10.5
|
-39.9 Milli second (msec)
Interval -68.8 to -10.9
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 2/ 24 h
|
-1.8 Milli second (msec)
Interval -35.1 to 31.5
|
-20.9 Milli second (msec)
Interval -45.3 to 3.5
|
-17.4 Milli second (msec)
Interval -50.6 to 15.7
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 2/ 36 h
|
-129.2 Milli second (msec)
Interval -170.7 to -87.7
|
-134.1 Milli second (msec)
Interval -170.1 to -98.0
|
-132.0 Milli second (msec)
Interval -177.0 to -87.1
|
|
Baseline-corrected RR Interval (ΔRR Interval)
Day 3/ 48 h
|
-76.0 Milli second (msec)
Interval -118.5 to -33.4
|
-63.2 Milli second (msec)
Interval -91.2 to -35.1
|
-81.3 Milli second (msec)
Interval -113.3 to -49.4
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (RR).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 0.5 h
|
6.7 msec
Interval -23.2 to 36.6
|
20.7 msec
Interval -10.5 to 51.9
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 1 h
|
22.2 msec
Interval -13.3 to 57.7
|
23.3 msec
Interval -9.5 to 56.0
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 1.5 h
|
38.9 msec
Interval -1.2 to 79.0
|
13.0 msec
Interval -15.3 to 41.2
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 2 h
|
26.9 msec
Interval -6.3 to 60.0
|
26.9 msec
Interval -2.2 to 55.9
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 3 h
|
25.1 msec
Interval -7.2 to 57.4
|
35.1 msec
Interval 5.7 to 64.4
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 4 h
|
-3.4 msec
Interval -36.4 to 29.6
|
18.8 msec
Interval -12.8 to 50.4
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 5 h
|
4.6 msec
Interval -44.5 to 53.8
|
17.8 msec
Interval -33.8 to 69.5
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 6 h
|
21.0 msec
Interval -16.1 to 58.2
|
19.7 msec
Interval -8.7 to 48.2
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 8 h
|
-12.8 msec
Interval -46.7 to 21.1
|
25.9 msec
Interval -14.5 to 66.3
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 1/ 12 h
|
36.5 msec
Interval -4.9 to 78.0
|
22.1 msec
Interval -18.6 to 62.9
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 2/ 24 h
|
15.1 msec
Interval -13.9 to 44.2
|
-6.8 msec
Interval -42.1 to 28.6
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 2/ 36 h
|
5.7 msec
Interval -26.0 to 37.3
|
-7.1 msec
Interval -50.7 to 36.6
|
—
|
|
Baseline-corrected and Placebo-adjusted RR Interval (ΔΔRR Interval)
Day 3/ 48 h
|
6.5 msec
Interval -29.9 to 42.9
|
14.8 msec
Interval -23.9 to 53.4
|
—
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (PR).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
n=24 Participants
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 0.5 h
|
-1.3 msec
Interval -2.8 to 0.2
|
-0.9 msec
Interval -2.7 to 1.0
|
-0.8 msec
Interval -2.0 to 0.3
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 1 h
|
-0.4 msec
Interval -2.3 to 1.5
|
-1.3 msec
Interval -3.1 to 0.5
|
-0.7 msec
Interval -1.6 to 0.3
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 1.5 h
|
-1.8 msec
Interval -4.1 to 0.5
|
-0.6 msec
Interval -2.5 to 1.3
|
-0.8 msec
Interval -2.2 to 0.5
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 2 h
|
-1.2 msec
Interval -3.6 to 1.1
|
-1.7 msec
Interval -4.2 to 0.7
|
0.2 msec
Interval -1.2 to 1.6
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 3 h
|
0.1 msec
Interval -1.7 to 1.9
|
-1.3 msec
Interval -3.2 to 0.7
|
-1.6 msec
Interval -3.1 to -0.1
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 4 h
|
-3.5 msec
Interval -6.4 to -0.5
|
-3.2 msec
Interval -5.7 to -0.7
|
-2.7 msec
Interval -6.1 to 0.6
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 5 h
|
-4.0 msec
Interval -6.3 to -1.6
|
-4.5 msec
Interval -7.0 to -2.0
|
-3.6 msec
Interval -6.6 to -0.6
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 6 h
|
-4.6 msec
Interval -6.1 to -3.1
|
-2.2 msec
Interval -4.9 to 0.5
|
-2.6 msec
Interval -4.7 to -0.4
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 8 h
|
-6.1 msec
Interval -9.4 to -2.8
|
-5.8 msec
Interval -8.4 to -3.1
|
-5.6 msec
Interval -8.8 to -2.3
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 1/ 12 h
|
-1.0 msec
Interval -3.9 to 1.8
|
-0.9 msec
Interval -3.3 to 1.5
|
-1.0 msec
Interval -4.1 to 2.2
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 2/ 24 h
|
-1.0 msec
Interval -3.6 to 1.5
|
-0.5 msec
Interval -2.5 to 1.5
|
-1.0 msec
Interval -3.4 to 1.3
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 2/ 36 h
|
0.5 msec
Interval -2.6 to 3.5
|
0.8 msec
Interval -2.2 to 3.7
|
-2.4 msec
Interval -6.5 to 1.7
|
|
Baseline-corrected PR Interval (ΔPR Interval)
Day 3/ 48 h
|
-0.7 msec
Interval -3.4 to 1.9
|
0.4 msec
Interval -2.7 to 3.6
|
-0.7 msec
Interval -3.3 to 1.8
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (PR).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 0.5 h
|
-0.5 msec
Interval -2.2 to 1.3
|
0.0 msec
Interval -2.1 to 2.1
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 1 h
|
0.3 msec
Interval -1.6 to 2.2
|
-0.3 msec
Interval -1.9 to 1.2
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 1.5 h
|
-0.7 msec
Interval -3.2 to 1.8
|
0.5 msec
Interval -1.7 to 2.7
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 2 h
|
-1.3 msec
Interval -3.8 to 1.3
|
-1.7 msec
Interval -4.1 to 0.7
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 3 h
|
1.7 msec
Interval -0.6 to 4.1
|
0.4 msec
Interval -2.4 to 3.2
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 4 h
|
-0.3 msec
Interval -3.1 to 2.5
|
0.2 msec
Interval -2.6 to 2.9
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 5 h
|
0.1 msec
Interval -3.2 to 3.4
|
-0.3 msec
Interval -3.0 to 2.4
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 6 h
|
-1.7 msec
Interval -3.7 to 0.3
|
0.4 msec
Interval -2.4 to 3.2
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 8 h
|
-0.1 msec
Interval -3.3 to 3.1
|
0.2 msec
Interval -2.7 to 3.1
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 1/ 12 h
|
-0.0 msec
Interval -2.7 to 2.6
|
0.3 msec
Interval -2.5 to 3.1
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 2/ 24 h
|
-0.0 msec
Interval -2.9 to 2.8
|
0.5 msec
Interval -2.0 to 3.0
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 2/ 36 h
|
3.1 msec
Interval -1.3 to 7.5
|
2.8 msec
Interval -1.7 to 7.3
|
—
|
|
Baseline-corrected and Placebo-adjusted PR Interval (ΔΔPR Interval)
Day 3/ 48 h
|
0.2 msec
Interval -2.8 to 3.2
|
0.9 msec
Interval -1.7 to 3.5
|
—
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (QRS).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
n=24 Participants
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 0.5 h
|
-0.5 msec
Interval -1.2 to 0.3
|
-0.6 msec
Interval -1.6 to 0.4
|
0.0 msec
Interval -0.6 to 0.6
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 1 h
|
-0.7 msec
Interval -1.4 to 0.0
|
-0.9 msec
Interval -1.8 to 0.0
|
0.1 msec
Interval -0.5 to 0.8
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 1.5 h
|
-0.5 msec
Interval -1.4 to 0.5
|
-0.5 msec
Interval -1.2 to 0.2
|
0.3 msec
Interval -0.3 to 1.0
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 2 h
|
0.0 msec
Interval -1.1 to 1.1
|
-0.8 msec
Interval -1.8 to 0.2
|
0.3 msec
Interval -0.4 to 1.1
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 3 h
|
-0.6 msec
Interval -1.7 to 0.4
|
-0.8 msec
Interval -1.9 to 0.2
|
-0.4 msec
Interval -1.2 to 0.3
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 4 h
|
1.3 msec
Interval 0.6 to 2.1
|
1.2 msec
Interval -0.3 to 2.7
|
1.7 msec
Interval 0.8 to 2.7
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 5 h
|
-0.3 msec
Interval -1.3 to 0.6
|
-0.6 msec
Interval -1.9 to 0.7
|
0.1 msec
Interval -1.2 to 1.3
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 6 h
|
-1.2 msec
Interval -1.9 to -0.5
|
-1.3 msec
Interval -2.2 to -0.3
|
-0.7 msec
Interval -1.9 to 0.5
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 8 h
|
-2.6 msec
Interval -3.7 to -1.6
|
-2.5 msec
Interval -3.4 to -1.6
|
-1.7 msec
Interval -3.3 to 0.0
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 1/ 12 h
|
-0.5 msec
Interval -1.2 to 0.3
|
-0.9 msec
Interval -2.0 to 0.2
|
-0.4 msec
Interval -1.4 to 0.7
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 2/ 24 h
|
-1.1 msec
Interval -1.8 to -0.3
|
-1.3 msec
Interval -2.0 to -0.5
|
-0.9 msec
Interval -1.8 to 0.0
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 2/ 36 h
|
-0.6 msec
Interval -1.4 to 0.2
|
-0.8 msec
Interval -2.0 to 0.4
|
-0.7 msec
Interval -1.9 to 0.4
|
|
Baseline-corrected QRS Interval (ΔQRS Interval)
Day 3/ 48 h
|
-1.0 msec
Interval -1.8 to -0.1
|
-0.7 msec
Interval -1.4 to 0.1
|
-0.7 msec
Interval -1.6 to 0.2
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (QRS).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 0.5 h
|
-0.4 msec
Interval -1.2 to 0.4
|
-0.7 msec
Interval -1.7 to 0.4
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 1 h
|
-0.9 msec
Interval -1.7 to 0.0
|
-1.1 msec
Interval -2.1 to -0.1
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 1.5 h
|
-0.8 msec
Interval -1.8 to 0.1
|
-0.8 msec
Interval -1.8 to 0.1
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 2 h
|
-0.4 msec
Interval -1.5 to 0.8
|
-1.2 msec
Interval -2.2 to -0.1
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 3 h
|
-0.2 msec
Interval -1.3 to 0.9
|
-0.4 msec
Interval -1.8 to 1.0
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 4 h
|
-0.4 msec
Interval -1.4 to 0.6
|
-0.7 msec
Interval -2.3 to 0.8
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 5 h
|
-0.4 msec
Interval -1.9 to 1.1
|
-0.8 msec
Interval -2.4 to 0.7
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 6 h
|
-0.5 msec
Interval -1.7 to 0.7
|
-0.6 msec
Interval -2.0 to 0.9
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 8 h
|
-1.0 msec
Interval -2.5 to 0.6
|
-0.9 msec
Interval -2.7 to 0.9
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 1/ 12 h
|
0.0 msec
Interval -1.2 to 1.2
|
-0.6 msec
Interval -2.0 to 0.9
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 2/ 24 h
|
-0.1 msec
Interval -1.1 to 1.0
|
-0.3 msec
Interval -1.5 to 0.9
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 2/ 36 h
|
0.1 msec
Interval -1.2 to 1.5
|
-0.0 msec
Interval -1.8 to 1.7
|
—
|
|
Baseline-corrected and Placebo-corrected QRS Interval (ΔΔQRS Interval)
Day 3/ 48 h
|
-0.2 msec
Interval -1.4 to 1.0
|
0.0 msec
Interval -1.2 to 1.3
|
—
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (QT).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
n=24 Participants
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 8 h
|
-31.1 msec
Interval -38.0 to -24.2
|
-22.9 msec
Interval -28.3 to -17.5
|
-23.9 msec
Interval -28.8 to -19.0
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 0.5 h
|
0.2 msec
Interval -3.5 to 3.9
|
3.8 msec
Interval 0.3 to 7.4
|
0.4 msec
Interval -2.8 to 3.6
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 1 h
|
1.5 msec
Interval -1.7 to 4.7
|
4.5 msec
Interval 1.4 to 7.5
|
2.1 msec
Interval -1.5 to 5.8
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 1.5 h
|
4.8 msec
Interval -0.5 to 10.1
|
5.4 msec
Interval 1.8 to 9.0
|
3.7 msec
Interval 0.6 to 6.7
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 2 h
|
5.0 msec
Interval 0.3 to 9.8
|
7.3 msec
Interval 4.3 to 10.3
|
5.3 msec
Interval 1.5 to 9.2
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 3 h
|
2.1 msec
Interval -2.2 to 6.5
|
4.5 msec
Interval 0.5 to 8.5
|
1.8 msec
Interval -2.3 to 6.0
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 4 h
|
-19.9 msec
Interval -27.2 to -12.6
|
-12.7 msec
Interval -19.0 to -6.4
|
-15.6 msec
Interval -20.9 to -10.4
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 5 h
|
-19.5 msec
Interval -26.4 to -12.6
|
-14.1 msec
Interval -19.4 to -8.8
|
-15.9 msec
Interval -20.5 to -11.4
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 6 h
|
-16.0 msec
Interval -21.9 to -10.2
|
-11.0 msec
Interval -15.8 to -6.1
|
-12.7 msec
Interval -17.2 to -8.2
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 1/ 12 h
|
-0.7 msec
Interval -6.0 to 4.5
|
0.3 msec
Interval -5.2 to 5.8
|
0.3 msec
Interval -4.9 to 5.4
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 2/ 24 h
|
-4.9 msec
Interval -10.3 to 0.5
|
-2.7 msec
Interval -6.9 to 1.6
|
-2.5 msec
Interval -7.0 to 2.1
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 2/ 36 h
|
-24.8 msec
Interval -33.6 to -16.0
|
-24.1 msec
Interval -29.1 to -19.1
|
-21.6 msec
Interval -29.4 to -13.8
|
|
Baseline-corrected QT Interval (ΔQT Interval)
Day 3/ 48 h
|
-16.0 msec
Interval -22.8 to -9.3
|
-10.0 msec
Interval -14.4 to -5.7
|
-10.7 msec
Interval -15.3 to -6.0
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (QT).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 0.5 h
|
-0.3 msec
Interval -4.6 to 4.1
|
3.0 msec
Interval -2.0 to 8.1
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 1 h
|
-0.7 msec
Interval -5.8 to 4.3
|
2.1 msec
Interval -3.1 to 7.3
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 1.5 h
|
1.0 msec
Interval -4.7 to 6.7
|
1.7 msec
Interval -3.7 to 7.1
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 2 h
|
-0.7 msec
Interval -5.8 to 4.4
|
1.7 msec
Interval -3.5 to 6.8
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 3 h
|
0.3 msec
Interval -4.7 to 5.3
|
2.3 msec
Interval -3.2 to 7.9
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 4 h
|
-4.3 msec
Interval -8.7 to 0.0
|
2.1 msec
Interval -3.2 to 7.4
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 5 h
|
-3.4 msec
Interval -10.5 to 3.8
|
1.4 msec
Interval -5.6 to 8.4
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 6 h
|
-3.6 msec
Interval -9.1 to 1.9
|
1.7 msec
Interval -3.1 to 6.6
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 8 h
|
-7.2 msec
Interval -13.1 to -1.4
|
0.8 msec
Interval -6.4 to 8.0
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 1/ 12 h
|
-0.8 msec
Interval -7.1 to 5.5
|
-0.4 msec
Interval -8.0 to 7.2
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 2/ 24 h
|
-2.5 msec
Interval -6.5 to 1.4
|
-0.5 msec
Interval -6.5 to 5.6
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 2/ 36 h
|
-3.3 msec
Interval -8.4 to 1.8
|
-3.0 msec
Interval -10.2 to 4.3
|
—
|
|
Baseline-corrected and Placebo-corrected QT Interval (ΔΔQT Interval)
Day 3/ 48 h
|
-5.7 msec
Interval -11.3 to 0.0
|
0.3 msec
Interval -6.1 to 6.7
|
—
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (QTcF).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
n=24 Participants
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 0.5 h
|
-1.7 msec
Interval -4.6 to 1.3
|
-0.3 msec
Interval -2.3 to 1.7
|
-0.5 msec
Interval -2.3 to 1.2
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 1 h
|
-0.4 msec
Interval -1.7 to 0.9
|
2.3 msec
Interval 0.6 to 4.0
|
3.1 msec
Interval 1.2 to 5.0
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 1.5 h
|
-1.0 msec
Interval -3.8 to 1.9
|
2.7 msec
Interval -0.3 to 5.6
|
2.9 msec
Interval 1.2 to 4.6
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 2 h
|
0.5 msec
Interval -1.7 to 2.8
|
2.5 msec
Interval 0.7 to 4.3
|
4.6 msec
Interval 2.1 to 7.1
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 3 h
|
0.7 msec
Interval -2.1 to 3.5
|
1.2 msec
Interval -0.9 to 3.3
|
3.3 msec
Interval 0.9 to 5.6
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 4 h
|
-0.6 msec
Interval -4.2 to 2.9
|
2.3 msec
Interval -2.4 to 7.0
|
2.7 msec
Interval 0.2 to 5.2
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 5 h
|
-6.3 msec
Interval -9.1 to -3.6
|
-2.5 msec
Interval -6.6 to 1.6
|
-2.5 msec
Interval -5.2 to 0.3
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 6 h
|
-10.0 msec
Interval -13.5 to -6.6
|
-5.7 msec
Interval -9.7 to -1.6
|
-4.0 msec
Interval -7.1 to -1.0
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 8 h
|
-12.1 msec
Interval -16.7 to -7.5
|
-10.0 msec
Interval -14.2 to -5.9
|
-7.0 msec
Interval -10.6 to -3.4
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 1/ 12 h
|
0.2 msec
Interval -3.2 to 3.6
|
2.2 msec
Interval -2.1 to 6.4
|
5.3 msec
Interval 2.1 to 8.5
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 2/ 24 h
|
-4.8 msec
Interval -8.3 to -1.3
|
0.2 msec
Interval -2.6 to 2.9
|
0.0 msec
Interval -2.1 to 2.2
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 2/ 36 h
|
-7.6 msec
Interval -12.6 to -2.6
|
-6.1 msec
Interval -10.0 to -2.1
|
-3.7 msec
Interval -7.5 to 0.2
|
|
Baseline-corrected QTcF Interval (ΔQTcF Interval)
Day 3/ 48 h
|
-5.8 msec
Interval -9.1 to -2.5
|
-2.0 msec
Interval -5.1 to 1.1
|
0.3 msec
Interval -2.3 to 2.8
|
SECONDARY outcome
Timeframe: Baseline; Day 1: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dosePopulation: The PD Analysis Set consisted of all participants in the Safety Analysis Set for whom baseline and post-baseline QTcF results from smoothed dECG data were available for at least 1 treatment period and who had no major protocol deviations thought to impact the analysis of the dECG data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for that particular day and time.
Investigation of the effect of verinurad given either as a 24 mg ER8 formulation (clinical exposure) or a 40 mg IR formulation (exposure needed to waive positive control as per question 5.1 of ICH E14 Q\&A), both in combination with allopurinol 300 mg, on additional dECG variable (QTcF).
Outcome measures
| Measure |
Treatment A
n=24 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 6 h
|
-6.1 msec
Interval -9.1 to -3.2
|
-1.3 msec
Interval -4.5 to 1.8
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 0.5 h
|
-1.2 msec
Interval -4.8 to 2.4
|
-0.0 msec
Interval -2.8 to 2.7
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 1 h
|
-3.4 msec
Interval -5.7 to -1.0
|
-0.9 msec
Interval -3.5 to 1.8
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 1.5 h
|
-3.7 msec
Interval -6.9 to -0.4
|
-0.1 msec
Interval -3.6 to 3.5
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 2 h
|
-4.1 msec
Interval -7.1 to -1.2
|
-2.1 msec
Interval -5.2 to 1.1
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 3 h
|
-2.8 msec
Interval -6.9 to 1.3
|
-2.2 msec
Interval -5.4 to 1.0
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 4 h
|
-3.6 msec
Interval -6.2 to -1.0
|
-0.9 msec
Interval -4.7 to 2.9
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 5 h
|
-3.7 msec
Interval -7.2 to -0.2
|
-0.3 msec
Interval -4.6 to 3.9
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 8 h
|
-5.4 msec
Interval -8.5 to -2.3
|
-3.0 msec
Interval -6.5 to 0.5
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 1/ 12 h
|
-5.2 msec
Interval -8.6 to -1.8
|
-3.4 msec
Interval -8.1 to 1.2
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 2/ 24 h
|
-4.8 msec
Interval -8.3 to -1.3
|
0.3 msec
Interval -2.4 to 3.0
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 2/ 36 h
|
-4.4 msec
Interval -8.1 to -0.6
|
-2.2 msec
Interval -6.7 to 2.2
|
—
|
|
Baseline-corrected and Placebo-corrected QTcF Interval (ΔΔQTcF Interval)
Day 3/ 48 h
|
-6.4 msec
Interval -9.7 to -3.1
|
-2.1 msec
Interval -5.5 to 1.3
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol.
Assessment of the pharmacokinetic (PK) of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Verinurad
|
393.8 h*ng/mL
Geometric Coefficient of Variation 34.99
|
918.7 h*ng/mL
Geometric Coefficient of Variation 26.53
|
—
|
|
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M1
|
413.7 h*ng/mL
Geometric Coefficient of Variation 41.20
|
904.8 h*ng/mL
Geometric Coefficient of Variation 34.49
|
—
|
|
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M8
|
447.2 h*ng/mL
Geometric Coefficient of Variation 32.30
|
895.0 h*ng/mL
Geometric Coefficient of Variation 23.75
|
—
|
|
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Allopurinol
|
4501 h*ng/mL
Geometric Coefficient of Variation 37.83
|
4617 h*ng/mL
Geometric Coefficient of Variation 32.39
|
—
|
|
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Oxypurinol
|
151100 h*ng/mL
Geometric Coefficient of Variation 16.74
|
145000 h*ng/mL
Geometric Coefficient of Variation 17.02
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol.
Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-t]) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M8
|
394.5 h*ng/mL
Geometric Coefficient of Variation 30.32
|
847.8 h*ng/mL
Geometric Coefficient of Variation 25.35
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-t]) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Verinurad
|
360.2 h*ng/mL
Geometric Coefficient of Variation 32.95
|
880.4 h*ng/mL
Geometric Coefficient of Variation 26.67
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-t]) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M1
|
383.2 h*ng/mL
Geometric Coefficient of Variation 40.00
|
865.4 h*ng/mL
Geometric Coefficient of Variation 35.23
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-t]) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Allopurinol
|
4408 h*ng/mL
Geometric Coefficient of Variation 38.00
|
4524 h*ng/mL
Geometric Coefficient of Variation 32.53
|
—
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC[0-t]) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Oxypurinol
|
136000 h*ng/mL
Geometric Coefficient of Variation 15.67
|
131400 h*ng/mL
Geometric Coefficient of Variation 15.12
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol.
Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Verinurad
|
56.57 ng/mL
Geometric Coefficient of Variation 36.34
|
459.7 ng/mL
Geometric Coefficient of Variation 47.74
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M1
|
54.92 ng/mL
Geometric Coefficient of Variation 39.54
|
364.4 ng/mL
Geometric Coefficient of Variation 48.92
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M8
|
54.80 ng/mL
Geometric Coefficient of Variation 31.28
|
297.8 ng/mL
Geometric Coefficient of Variation 39.44
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Allopurinol
|
1610 ng/mL
Geometric Coefficient of Variation 41.61
|
1780 ng/mL
Geometric Coefficient of Variation 38.53
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Oxypurinol
|
7591 ng/mL
Geometric Coefficient of Variation 16.77
|
7528 ng/mL
Geometric Coefficient of Variation 20.28
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol.
Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Verinurad
|
5.00 Hour
Interval 3.0 to 12.0
|
1.02 Hour
Interval 0.5 to 2.0
|
—
|
|
Time to Reach Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M1
|
5.00 Hour
Interval 3.0 to 12.0
|
1.50 Hour
Interval 1.0 to 2.0
|
—
|
|
Time to Reach Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M8
|
5.00 Hour
Interval 4.0 to 12.0
|
1.50 Hour
Interval 1.0 to 2.0
|
—
|
|
Time to Reach Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Allopurinol
|
1.50 Hour
Interval 0.5 to 3.0
|
1.50 Hour
Interval 0.5 to 2.0
|
—
|
|
Time to Reach Maximum Plasma Concentration (Tmax) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Oxypurinol
|
5.00 Hour
Interval 1.5 to 6.0
|
3.00 Hour
Interval 1.5 to 5.0
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol.
Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Time Delay Between Drug Administration and the First Observed Concentration in Plasma (Tlag) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Verinurad
|
0.50 Hour
Interval 0.0 to 0.5
|
0.00 Hour
Interval 0.0 to 0.0
|
—
|
|
Time Delay Between Drug Administration and the First Observed Concentration in Plasma (Tlag) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M1
|
0.50 Hour
Interval 0.0 to 1.0
|
0.00 Hour
Interval 0.0 to 0.0
|
—
|
|
Time Delay Between Drug Administration and the First Observed Concentration in Plasma (Tlag) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M8
|
0.50 Hour
Interval 0.0 to 1.0
|
0.00 Hour
Interval 0.0 to 0.0
|
—
|
|
Time Delay Between Drug Administration and the First Observed Concentration in Plasma (Tlag) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Allopurinol
|
0.00 Hour
Interval 0.0 to 0.5
|
0.00 Hour
Interval 0.0 to 0.0
|
—
|
|
Time Delay Between Drug Administration and the First Observed Concentration in Plasma (Tlag) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Oxypurinol
|
0.00 Hour
Interval 0.0 to 0.0
|
0.00 Hour
Interval 0.0 to 0.0
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol.
Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Terminal Half-life (t½λz) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Verinurad
|
14.92 Hour
Standard Deviation 5.355
|
13.33 Hour
Standard Deviation 5.705
|
—
|
|
Terminal Half-life (t½λz) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M1
|
14.30 Hour
Standard Deviation 4.991
|
12.65 Hour
Standard Deviation 4.354
|
—
|
|
Terminal Half-life (t½λz) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M8
|
16.89 Hour
Standard Deviation 8.832
|
13.96 Hour
Standard Deviation 4.065
|
—
|
|
Terminal Half-life (t½λz) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Allopurinol
|
1.020 Hour
Standard Deviation 0.2327
|
1.012 Hour
Standard Deviation 0.1090
|
—
|
|
Terminal Half-life (t½λz) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Oxypurinol
|
14.27 Hour
Standard Deviation 4.119
|
13.41 Hour
Standard Deviation 2.735
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/M1/M8/allopurinol/oxypurinol.
Assessment of the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Time of Last Quantifiable Plasma Concentration (Tlast) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Verinurad
|
48.05 Hour
Interval 48.0 to 48.13
|
48.07 Hour
Interval 48.02 to 48.18
|
—
|
|
Time of Last Quantifiable Plasma Concentration (Tlast) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M1
|
48.05 Hour
Interval 48.0 to 48.13
|
48.07 Hour
Interval 48.02 to 48.18
|
—
|
|
Time of Last Quantifiable Plasma Concentration (Tlast) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
M8
|
48.05 Hour
Interval 48.0 to 48.13
|
48.07 Hour
Interval 48.02 to 48.18
|
—
|
|
Time of Last Quantifiable Plasma Concentration (Tlast) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Allopurinol
|
8.00 Hour
Interval 6.0 to 8.02
|
7.03 Hour
Interval 6.0 to 8.03
|
—
|
|
Time of Last Quantifiable Plasma Concentration (Tlast) for Verinurad, M1, M8, Allopurinol, and Oxypurinol
Oxypurinol
|
48.05 Hour
Interval 48.0 to 48.13
|
48.07 Hour
Interval 48.02 to 48.18
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/allopurinol.
Assessment of the PK of verinurad and allopurinol in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (Parent Drug Only) (CL/F) for Verinurad and Allopurinol
Verinurad
|
64.07 Liter/Hour
Standard Deviation 19.43
|
45.09 Liter/Hour
Standard Deviation 13.13
|
—
|
|
Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (Parent Drug Only) (CL/F) for Verinurad and Allopurinol
Allopurinol
|
71.03 Liter/Hour
Standard Deviation 26.45
|
68.08 Liter/Hour
Standard Deviation 21.28
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/allopurinol.
Assessment of the PK of verinurad and allopurinol in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Parent Drug Only) (Vz/F) for Verinurad and Allopurinol
Verinurad
|
1342 Liter
Standard Deviation 500.1
|
856.1 Liter
Standard Deviation 413.5
|
—
|
|
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Parent Drug Only) (Vz/F) for Verinurad and Allopurinol
Allopurinol
|
103.6 Liter
Standard Deviation 45.48
|
97.96 Liter
Standard Deviation 28.94
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/allopurinol.
Assessment of the PK of verinurad and allopurinol in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Apparent Volume of Distribution at Steady State Following Extravascular Administration (Parent Drug Only) (Vss/F) for Verinurad and Allopurinol
Verinurad
|
1060 Liter
Standard Deviation 336.6
|
448.6 Liter
Standard Deviation 227.5
|
—
|
|
Apparent Volume of Distribution at Steady State Following Extravascular Administration (Parent Drug Only) (Vss/F) for Verinurad and Allopurinol
Allopurinol
|
182.9 Liter
Standard Deviation 79.88
|
165.3 Liter
Standard Deviation 61.06
|
—
|
SECONDARY outcome
Timeframe: Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dosePopulation: The PK Analysis Set consisted of all participants in the Safety Analysis Set for whom at least 1 reportable PK parameter could be calculated and who had no major protocol deviations thought to impact the analysis of the PK data. Here, number analyzed in each row signifies only the participants with available data that were analyzed for Verinurad/allopurinol.
Assessment of the PK of verinurad and allopurinol in healthy participants.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRT) for Verinurad and Oxypurinol
Verinurad
|
16.47 Hour
Geometric Coefficient of Variation 26.78
|
9.320 Hour
Geometric Coefficient of Variation 34.79
|
—
|
|
Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRT) for Verinurad and Oxypurinol
Allopurinol
|
2.517 Hour
Geometric Coefficient of Variation 24.44
|
2.383 Hour
Geometric Coefficient of Variation 18.95
|
—
|
SECONDARY outcome
Timeframe: From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug (verinurad, allopurinol, and placebo) and for whom any safety post-dose data were available.
Examination of the safety and tolerability of verinurad and allopurinol.
Outcome measures
| Measure |
Treatment A
n=22 Participants
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 Participants
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
n=23 Participants
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Any AE
|
8 Participants
|
4 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any AE leading to withdrawal from study
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any AE with outcome = death
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any Serious adverse events (including events with outcome = death)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs)
Any AE leading to discontinuation of study drug
|
0 Participants
|
1 Participants
|
0 Participants
|
Adverse Events
Treatment A
Treatment B
Treatment C
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=22 participants at risk
Participants received a single dose of verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
|
Treatment B
n=24 participants at risk
Participants received a single dose of verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
|
Treatment C
n=23 participants at risk
Participants received matching placebos for both verinurad and allopurinol
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
18.2%
4/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
12.5%
3/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
8.7%
2/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Nervous system disorders
Somnolence
|
0.00%
0/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.2%
1/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Gastrointestinal disorders
Abdominal pain lower
|
4.5%
1/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.2%
1/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Gastrointestinal disorders
Nausea
|
4.5%
1/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.3%
1/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.3%
1/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.2%
1/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Renal and urinary disorders
Urine odour abnormal
|
0.00%
0/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.3%
1/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Eye disorders
Ocular hyperaemia
|
9.1%
2/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.5%
1/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.2%
1/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
General disorders
Medical device site reaction
|
4.5%
1/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.3%
1/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
|
Infections and infestations
Otitis externa
|
0.00%
0/22 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
4.2%
1/24 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
0.00%
0/23 • From Screening (Day -28 to Day -2) until the Follow-up visit (7 to 10 Days After the Last Dose)
|
Additional Information
Global Clinical Lead
AstraZeneca Clinical Study Information Center
Results disclosure agreements
- Principal investigator is a sponsor employee No unpublished information may be disclosed without prior written approval from AstraZeneca AB.
- Publication restrictions are in place
Restriction type: OTHER