Trial Outcomes & Findings for A Study to Assess the Pharmacodynamic Effect of Single Doses of AZD9977 in Healthy Male Subjects (NCT NCT02532998)
NCT ID: NCT02532998
Last Updated: 2017-03-29
Results Overview
The sum over the urine collection intervals of the logarithm of the urinary sodium/potassium ratio from two hours to eight hours post-dose. NOTE: Data are presented as the sum of the difference between ln(Na+) and ln(K+) over the collected intervals 2-4, 4-6 and 6-8 hours.
COMPLETED
PHASE1
40 participants
From 2 hours post dose to 8 hours post dose
2017-03-29
Participant Flow
This study was conducted at PAREXEL Early Phase Clinical Unit London, United Kingdom
This study had a single-blind, randomized, 4-treatment, 4-period crossover design (William's design). A total of 40 participants were enrolled (signed ICF) in this study, of which 23 participants were randomized to receive the study medication.
Participant milestones
| Measure |
All Particpants
Twenty three healthy male participants aged 18 to 50 years who satisfied all the study inclusion criteria were included in the study
|
|---|---|
|
Overall Study
STARTED
|
23
|
|
Overall Study
COMPLETED
|
23
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess the Pharmacodynamic Effect of Single Doses of AZD9977 in Healthy Male Subjects
Baseline characteristics by cohort
| Measure |
All Particpants
n=23 Participants
Twenty three healthy male participants aged 18 to 50 years who satisfied all the study inclusion criteria were included in the study
|
|---|---|
|
Age, Continuous
|
36 years
STANDARD_DEVIATION 8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The pharmacodynamic (PD) analysis set consisted of all participants in the safety analysis set (SAF) with at least one evaluable sum of the logarithm of the sodium/potassium ratio from two hours up to eight hours post dose, and who had no major protocol deviations thought to impact on the analysis of the PD data.
The sum over the urine collection intervals of the logarithm of the urinary sodium/potassium ratio from two hours to eight hours post-dose. NOTE: Data are presented as the sum of the difference between ln(Na+) and ln(K+) over the collected intervals 2-4, 4-6 and 6-8 hours.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977.
|
-0.545 sodium/potassium ratio
Standard Deviation 1.19
|
0.694 sodium/potassium ratio
Standard Deviation 1.18
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The AZD9977 PK analysis set consisted of all participants who received at least one dose of AZD9977 for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the AZD9977 PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Observed Maximum Concentration (Cmax) of AZD9977
|
6238 nmol/L
Geometric Coefficient of Variation 16.7
|
5816 nmol/L
Geometric Coefficient of Variation 22.2
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The AZD9977 PK analysis set consisted of all participants who received at least one dose of AZD9977 for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the AZD9977 PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=22 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=21 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977.
|
21060 h*nmol/L
Geometric Coefficient of Variation 18.4
|
19120 h*nmol/L
Geometric Coefficient of Variation 23.9
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The AZD9977 PK analysis set consisted of all participants who received at least one dose of AZD9977 for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the AZD9977 PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC[0-t]) of AZD9977.
|
19970 h*nmol/L
Geometric Coefficient of Variation 20.3
|
18520 h*nmol/L
Geometric Coefficient of Variation 23.6
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The AZD9977 PK analysis set consisted of all subjects who received at least one dose of AZD9977 for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the AZD9977 PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Time to Reach Maximum Concentration (Tmax) of AZD9977.
|
0.52 h
Interval 0.48 to 1.02
|
0.50 h
Interval 0.48 to 2.5
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The AZD9977 PK analysis set consisted of all participants who received at least one dose of AZD9977 for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the AZD9977 PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=22 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=21 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Terminal Half-life (t½λz) of AZD9977.
|
6.753 h
Standard Deviation 2.322
|
6.726 h
Standard Deviation 1.719
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The AZD9977 PK analysis set consisted of all participants who received at least one dose of AZD9977 for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the AZD9977 PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=22 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=21 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Apparent Clearance (CL/F) of AZD9977.
|
23.78 L/h
Geometric Coefficient of Variation 18.4
|
26.20 L/h
Geometric Coefficient of Variation 23.9
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The AZD9977 PK analysis set consisted of all participants who received at least one dose of AZD9977 for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the AZD9977 PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=21 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=22 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977.
|
246.7 L
Geometric Coefficient of Variation 42.4
|
220.4 L
Geometric Coefficient of Variation 34.3
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The eplerenone PK analysis set consisted of all participants who received at least one dose of eplerenone for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the eplerenone PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone.
|
49.11 L
Geometric Coefficient of Variation 19.2
|
44.77 L
Geometric Coefficient of Variation 19.3
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The eplerenone PK analysis set consisted of all participants who received at least one dose of eplerenone for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the eplerenone PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Apparent Clearance (CL/F) of Eplerenone.
|
10.87 L/h
Geometric Coefficient of Variation 34.4
|
9.360 L/h
Geometric Coefficient of Variation 35.9
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The eplerenone PK analysis set consisted of all participants who received at least one dose of eplerenone for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the eplerenone PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Terminal Half-life (t½λz) of Eplerenone.
|
3.232 h
Standard Deviation 0.8305
|
3.419 h
Standard Deviation 0.8843
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The eplerenone PK analysis set consisted of all participants who received at least one dose of eplerenone for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the eplerenone PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Time to Reach Maximum Concentration (Tmax) of Eplerenone.
|
1.98 h
Interval 0.48 to 3.98
|
2.00 h
Interval 0.97 to 3.98
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The eplerenone PK analysis set consisted of all participants who received at least one dose of eplerenone for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the eplerenone PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Observed Maximum Concentration (Cmax) of Eplerenone.
|
1557 ng/mL
Geometric Coefficient of Variation 26.1
|
1729 ng/mL
Geometric Coefficient of Variation 23.2
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The eplerenone PK analysis set consisted of all participants who received at least one dose of eplerenone for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the eplerenone PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC(0-t)) of Eplerenone.
|
9035 h*ng/mL
Geometric Coefficient of Variation 33.9
|
10510 h*ng/mL
Geometric Coefficient of Variation 34.6
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The eplerenone PK analysis set consisted of all participants who received at least one dose of eplerenone for whom at least one of the primary PK parameters was evaluable and who had no major protocol deviations thought to impact on the analysis of the eplerenone PK data.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone.
|
9199 h*ng/mL
Geometric Coefficient of Variation 34.4
|
10680 h*ng/mL
Geometric Coefficient of Variation 35.9
|
—
|
—
|
SECONDARY outcome
Timeframe: From 2 hours post dose to 8 hours post dosePopulation: The pharmacodynamic (PD) analysis set consisted of all participants in the safety analysis set (SAF) with at least one evaluable sum of the logarithm of the sodium/potassium ratio from two hours up to eight hours post dose, and who had no major protocol deviations thought to impact on the analysis of the PD data.
The sum over the urine collection intervals of the logarithm of the urinary sodium/potassium ratio from two hours to eight hours post-dose. NOTE: Note: Data are presented as the sum of the difference between ln(Na+) and ln(K+) over the collected intervals 2-4, 4-6 and 6-8 hours.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
Participants received fludrocortisone + AZD9977
|
Treatment C
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in AZD9977 Treatment With Placebo Versus Treatment With AZD9977.
|
-4.09 sodium/potassium ratio
Standard Deviation 2.11
|
-0.694 sodium/potassium ratio
Standard Deviation 1.27
|
—
|
—
|
SECONDARY outcome
Timeframe: From screening to post-study visit, up to 10 weeksPopulation: The safety analysis set (SAF) included all participants who received at least one dose of any of the administered products (fludrocortisone, eplerenone or AZD9977/matching placebo) and for whom any safety data post-fludrocortisone dose were available.
Clinically significant blood pressure values (if available) were recorded for all participants. The systolic blood pressure (mmHg) and diastolic BP (mmHg) was obtained after each subject had rested in the supine position for at least 5 minutes and was performed in accordance with the Schedule of Assessments of study protocol. Abnormal findings in blood pressure after 10 minutes resting in the supine position was defined as following: * Systolic blood pressure (SBP) \< 90 mmHg or ≥ 140 mmHg * Diastolic blood pressure (DBP) \< 50 mmHg or ≥ 90 mmHg.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Blood Pressure Values.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From screening to post-study visit, up to 10 weeksPopulation: The SAF included all subjects who received at least one dose of any of the administered products (fludrocortisone, eplerenone or AZD9977/matching placebo) and for whom any safety data post-fludrocortisone dose were available.
Clinically significant pulse rate (if available) was recorded for all participants in the study. The pulse was obtained after each subject had rested in the supine position for at least 5 minutes and was performed in accordance with the Schedule of Assessments of study protocol. Abnormal findings in pulse rate, after 10 minutes resting in the supine position, was defined as following: • Pulse \< 45 or \> 85 beats per minute (bpm)
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Pulse Rate.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From screening to post-study visit, up to 10 weeksPopulation: The SAF included all participants who received at least one dose of any of the administered products (fludrocortisone, eplerenone or AZD9977/matching placebo) and for whom any safety data post-fludrocortisone dose were available.
Clinically significant electrocardiogram values were recorded for all participants in the study. A 12-lead ECG was obtained after each subject had rested in the supine position for at least 10 minutes and was performed in accordance with the Schedule of Assessments of study protocol. The investigator judged the overall interpretation as normal or abnormal. If abnormal, it would have been decided as to whether or not the abnormality was clinically significant and the reason for the abnormality would have been recorded. The investigator could add extra 12-lead resting ECG safety assessments if there were any abnormal findings of if the investigator considered it was necessary for any other safety reason. These assessments would have been entered as an unscheduled assessment.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Electrocardiogram.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From screening to post-study visit, up to 10 weeksPopulation: The SAF included all participants who received at least one dose of any of the administered products (fludrocortisone, eplerenone or AZD9977/matching placebo) and for whom any safety data post-fludrocortisone dose were available.
Number of participants with clinically significant physical examination values. The complete physical examinations included an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, mouth and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. The brief physical examinations included an assessment of the general appearance, skin, abdomen, cardiovascular and respiratory systems. The results of the physical examination were listed by body system for each subject. Body weight was listed by participant and time-point. Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the baseline assessment were reported as an adverse event (AE).
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Physical Examination Values.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From screening to post-study visit, up to 10 weeksPopulation: The SAF included all participants who received at least one dose of any of the administered products (fludrocortisone, eplerenone or AZD9977/matching placebo) and for whom any safety data post-fludrocortisone dose were available.
Clinically significant safety laboratory test values included hematology, clinical chemistry, urinalysis and urine chemistry, including urine creatinine and uric acid measurements. Viral serology and urine drugs of abuse, alcohol and cotinine were assessed for eligibility. If deterioration in laboratory value was associated with clinical symptoms and/or signs, the symptom or sign were reported as an adverse event and the associated laboratory result was considered as additional information. Laboratory results were listed and summarized according to change from baseline and repeat/unscheduled measurements. Any out of range laboratory results were flagged in the individual listings.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Safety Laboratory Tests Values.
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From 0 to 8 hours after dosingPopulation: The PD analysis set consisted of all participants in the SAF with at least one evaluable sum of the logarithm of the sodium/potassium ratio from two hours up to eight hours post dose, and who had no major protocol deviations thought to impact on the analysis of the PD data.
Pharmacodynamics of AZD9977 by assessment of fractional sodium excretion in urine for each urine collection time interval. Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval.
0 to 2 hours
|
0.34 % value
Standard Deviation 0.18
|
0.33 % value
Standard Deviation 0.19
|
0.32 % value
Standard Deviation 0.09
|
0.33 % value
Standard Deviation 0.20
|
|
Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval.
2 to 4 hours
|
0.22 % value
Standard Deviation 0.15
|
0.48 % value
Standard Deviation 0.21
|
0.35 % value
Standard Deviation 0.12
|
0.37 % value
Standard Deviation 0.17
|
|
Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval.
4 to 6 hours
|
0.15 % value
Standard Deviation 0.12
|
0.58 % value
Standard Deviation 0.19
|
0.36 % value
Standard Deviation 0.13
|
0.38 % value
Standard Deviation 0.14
|
|
Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval.
6 to 8 hours
|
0.16 % value
Standard Deviation 0.15
|
0.66 % value
Standard Deviation 0.23
|
0.36 % value
Standard Deviation 0.16
|
0.48 % value
Standard Deviation 0.23
|
SECONDARY outcome
Timeframe: From 0 to 24 hours after dosingPopulation: The PD analysis set consisted of all participants in the SAF with at least one evaluable sum of the logarithm of the sodium/potassium ratio from two hours up to eight hours post dose, and who had no major protocol deviations thought to impact on the analysis of the PD data.
Pharmacodynamics of AZD9977 by assessment of total sodium excreted cumulatively and during each of the urine collection intervals. Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
2 to 4 hours
|
12 mmol
Standard Deviation 6
|
17 mmol
Standard Deviation 7
|
15 mmol
Standard Deviation 5
|
15 mmol
Standard Deviation 7
|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
4 to 6 hours
|
15 mmol
Standard Deviation 8
|
31 mmol
Standard Deviation 12
|
23 mmol
Standard Deviation 8
|
23 mmol
Standard Deviation 8
|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
12 to 14 hours
|
32 mmol
Standard Deviation 17
|
82 mmol
Standard Deviation 22
|
51 mmol
Standard Deviation 14
|
62 mmol
Standard Deviation 19
|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
0 to 2 hours
|
7 mmol
Standard Deviation 3
|
8 mmol
Standard Deviation 6
|
7 mmol
Standard Deviation 3
|
7 mmol
Standard Deviation 4
|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
6 to 8 hours
|
19 mmol
Standard Deviation 10
|
46 mmol
Standard Deviation 14
|
32 mmol
Standard Deviation 10
|
34 mmol
Standard Deviation 10
|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
8 to 10 hours
|
23 mmol
Standard Deviation 12
|
63 mmol
Standard Deviation 17
|
39 mmol
Standard Deviation 12
|
47 mmol
Standard Deviation 14
|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
10 to 12 hours
|
28 mmol
Standard Deviation 14
|
74 mmol
Standard Deviation 19
|
46 mmol
Standard Deviation 13
|
55 mmol
Standard Deviation 16
|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
14 to 16 hours
|
36 mmol
Standard Deviation 18
|
87 mmol
Standard Deviation 23
|
54 mmol
Standard Deviation 15
|
67 mmol
Standard Deviation 21
|
|
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
16 to 24 hours
|
46 mmol
Standard Deviation 23
|
103 mmol
Standard Deviation 29
|
66 mmol
Standard Deviation 19
|
79 mmol
Standard Deviation 24
|
SECONDARY outcome
Timeframe: From 0 to 8 hours post dosingPopulation: The PD analysis set consisted of all participants in the SAF with at least one evaluable sum of the logarithm of the sodium/potassium ratio from two hours up to eight hours post dose, and who had no major protocol deviations thought to impact on the analysis of the PD data.
Pharmacodynamics of AZD9977 assessed per fractional potassium excretion in urine for each urine collection time interval. Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval.
0 to 2 hours
|
21.72 % value
Standard Deviation 6.49
|
22.19 % value
Standard Deviation 3.96
|
21.14 % value
Standard Deviation 5.74
|
21.66 % value
Standard Deviation 5.40
|
|
Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval.
2 to 4 hours
|
22.26 % value
Standard Deviation 4.22
|
20.30 % value
Standard Deviation 4.45
|
18.95 % value
Standard Deviation 2.78
|
21.15 % value
Standard Deviation 5.25
|
|
Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval.
4 to 6 hours
|
14.60 % value
Standard Deviation 3.19
|
12.49 % value
Standard Deviation 3.04
|
12.12 % value
Standard Deviation 3.03
|
12.48 % value
Standard Deviation 3.13
|
|
Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval.
6 to 8 hours
|
18.08 % value
Standard Deviation 4.64
|
13.35 % value
Standard Deviation 5.60
|
13.34 % value
Standard Deviation 4.56
|
13.48 % value
Standard Deviation 3.55
|
SECONDARY outcome
Timeframe: From 0 to 24 hours after dosingPopulation: The PD analysis set will consist of all participants in the SAF with at least one evaluable sum of the logarithm of the sodium/potassium ratio from two hours up to eight hours post dose, and who have no major protocol deviations thought to impact on the analysis of the PD data.
Pharmacodynamics of AZD9977 by assessment of total potassium excreted cumulatively and during each of the urine collection intervals. Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone in comparison to AZD9977 placebo.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
4 to 6 hours
|
38.3 mmol
Standard Deviation 11.1
|
35.2 mmol
Standard Deviation 6.8
|
35.5 mmol
Standard Deviation 8.8
|
35.9 mmol
Standard Deviation 9.2
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
14 to 16 hours
|
87.7 mmol
Standard Deviation 17.4
|
77.5 mmol
Standard Deviation 15.1
|
79.2 mmol
Standard Deviation 13.2
|
79.7 mmol
Standard Deviation 12.9
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
12 to 14 hours
|
80.7 mmol
Standard Deviation 17.5
|
71.3 mmol
Standard Deviation 15
|
72.5 mmol
Standard Deviation 13.1
|
73.5 mmol
Standard Deviation 12.6
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
0 to 2 hours
|
13.6 mmol
Standard Deviation 5.6
|
14.5 mmol
Standard Deviation 3.1
|
14.0 mmol
Standard Deviation 5.8
|
13.7 mmol
Standard Deviation 4.2
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
2 to 4 hours
|
29.0 mmol
Standard Deviation 9.4
|
26.7 mmol
Standard Deviation 5.7
|
27.1 mmol
Standard Deviation 7.7
|
27.4 mmol
Standard Deviation 7.6
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
6 to 8 hours
|
49.9 mmol
Standard Deviation 13.3
|
44.4 mmol
Standard Deviation 8.7
|
44.6 mmol
Standard Deviation 10.4
|
45.1 mmol
Standard Deviation 10.7
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
8 to 10 hours
|
61.4 mmol
Standard Deviation 14.7
|
54.4 mmol
Standard Deviation 10.2
|
53.8 mmol
Standard Deviation 11.0
|
54.9 mmol
Standard Deviation 11.0
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
10 to 12 hours
|
71.1 mmol
Standard Deviation 15.7
|
62.1 mmol
Standard Deviation 12.2
|
63.3 mmol
Standard Deviation 11.4
|
64.0 mmol
Standard Deviation 12.4
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
16 to 24 hours
|
101.8 mmol
Standard Deviation 17.7
|
92.1 mmol
Standard Deviation 13
|
94.4 mmol
Standard Deviation 15.5
|
95.4 mmol
Standard Deviation 12.0
|
SECONDARY outcome
Timeframe: From 8 hours before dosing until 24 hours after dosingPopulation: The PD analysis set consisted of all participants in the SAF with at least one evaluable sum of the logarithm of the sodium/potassium ratio from two hours up to eight hours post dose, and who had no major protocol deviations thought to impact on the analysis of the PD data.
Pharmacodynamics of AZD9977 assessed per urine production for each urine collection time interval. Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone.
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
0 to 2 hour
|
307.4 mL
Standard Deviation 78.4
|
320.2 mL
Standard Deviation 102.6
|
305.0 mL
Standard Deviation 89.5
|
298.8 mL
Standard Deviation 68.9
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
2 to 4 hour
|
272.2 mL
Standard Deviation 105.0
|
236.1 mL
Standard Deviation 80.1
|
245.6 mL
Standard Deviation 63.2
|
272.6 mL
Standard Deviation 85.8
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
6 to 8 hours
|
216.6 mL
Standard Deviation 99.3
|
115.7 mL
Standard Deviation 121.6
|
273.6 mL
Standard Deviation 96.6
|
291.5 mL
Standard Deviation 135.5
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
8 to 10 hours
|
266.0 mL
Standard Deviation 125.4
|
326.6 mL
Standard Deviation 111.7
|
246.6 mL
Standard Deviation 103.9
|
300.2 mL
Standard Deviation 121.1
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
16 to 24 hours
|
296.0 mL
Standard Deviation 184.1
|
302.8 mL
Standard Deviation 181.1
|
292.2 mL
Standard Deviation 164.8
|
290.6 mL
Standard Deviation 90.2
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
-8 to -2 hours
|
321.4 mL
Standard Deviation 208.3
|
309.3 mL
Standard Deviation 182.5
|
284.5 mL
Standard Deviation 186.4
|
294.9 mL
Standard Deviation 130.3
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
-2 to 0 hour
|
303.5 mL
Standard Deviation 111.7
|
288.6 mL
Standard Deviation 99.3
|
274.3 mL
Standard Deviation 113.7
|
284.5 mL
Standard Deviation 90.2
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
4 to 6 hours
|
178.8 mL
Standard Deviation 93.8
|
246.0 mL
Standard Deviation 115.7
|
229.9 mL
Standard Deviation 147.7
|
202.2 mL
Standard Deviation 99.5
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
10 to 12 hours
|
337.1 mL
Standard Deviation 132.0
|
361.9 mL
Standard Deviation 149.0
|
309.0 mL
Standard Deviation 137.4
|
324.5 mL
Standard Deviation 143.6
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
12 to 14 hours
|
280.2 mL
Standard Deviation 131.0
|
300.7 mL
Standard Deviation 141.8
|
306.0 mL
Standard Deviation 125.4
|
306.3 mL
Standard Deviation 152.2
|
|
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
14 to 16 hours
|
357.3 mL
Standard Deviation 124.8
|
345.9 mL
Standard Deviation 129.0
|
326.5 mL
Standard Deviation 115.3
|
354.2 mL
Standard Deviation 138.6
|
SECONDARY outcome
Timeframe: From 8 hours before dosing until 24 hours after dosingPopulation: The PD analysis set will consist of all participants in the SAF with at least one evaluable sum of the logarithm of the sodium/potassium ratio from two hours up to eight hours post dose, and who have no major protocol deviations thought to impact on the analysis of the PD data.
Pharmacodynamics of AZD9977 by assessment of total urine volume excreted cumulatively and during each of the urine collection intervals. Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone
Outcome measures
| Measure |
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977
|
Treatment B
n=23 Participants
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 Participants
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
|---|---|---|---|---|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
0 to 2 hour
|
307.4 mL
Standard Deviation 78.4
|
320.2 mL
Standard Deviation 102.6
|
305.0 mL
Standard Deviation 89.5
|
298.8 mL
Standard Deviation 68.9
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
2 to 4 hour
|
579.5 mL
Standard Deviation 127.2
|
556.3 mL
Standard Deviation 126.1
|
550.7 mL
Standard Deviation 109.2
|
571.4 mL
Standard Deviation 128.3
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
4 to 6 hours
|
758.3 mL
Standard Deviation 186.3
|
802.2 mL
Standard Deviation 189.7
|
780.6 mL
Standard Deviation 204.6
|
773.6 mL
Standard Deviation 184.1
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
6 to 8 hours
|
974.9 mL
Standard Deviation 235.6
|
1099.0 mL
Standard Deviation 199.1
|
1054.2 mL
Standard Deviation 201.4
|
1065.1 mL
Standard Deviation 261.1
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
8 to 10 hours
|
1242.2 mL
Standard Deviation 288.9
|
1425.2 mL
Standard Deviation 235.6
|
1300.8 mL
Standard Deviation 192.6
|
1365.3 mL
Standard Deviation 261.1
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
10 to 12 hours
|
1574.4 mL
Standard Deviation 329.0
|
1791.7 mL
Standard Deviation 283.6
|
1609.8 mL
Standard Deviation 264.2
|
1689.8 mL
Standard Deviation 300.9
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
12 to 14 hours
|
1865.1 mL
Standard Deviation 378.9
|
2091.7 mL
Standard Deviation 354.6
|
1915.8 mL
Standard Deviation 264.2
|
1996.1 mL
Standard Deviation 330.7
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
14 to 16 hours
|
2221.0 mL
Standard Deviation 340.7
|
2435.7 mL
Standard Deviation 304.4
|
2242.3 mL
Standard Deviation 233.3
|
2350.3 mL
Standard Deviation 316.6
|
|
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
16 to 24 hours
|
2506.6 mL
Standard Deviation 388.6
|
2741.2 mL
Standard Deviation 293.9
|
2534.5 mL
Standard Deviation 236.3
|
2640.9 mL
Standard Deviation 347.5
|
Adverse Events
Treatment A
Treatment B
Treatment C
Treatment D
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=23 participants at risk
Participants received fludrocortisone + AZD9977 Placebo
|
Treatment B
n=23 participants at risk
Participants received fludrocortisone + AZD9977
|
Treatment C
n=23 participants at risk
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
|
Treatment D
n=23 participants at risk
Participants received fludrocortisone + eplerenone + AZD9977
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Nervous system disorders
Headache
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
8.7%
2/23 • Number of events 2 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Nervous system disorders
Dizziness
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Gastrointestinal disorders
Abdominal distention
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Infections and infestations
Nasopharyngitis
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Eye disorders
Ocular hyperemia
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
General disorders
Pyrexia
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Injury, poisoning and procedural complications
Splinter
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
0.00%
0/23 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
4.3%
1/23 • Number of events 1 • SAEs will be collected from the signing of informed consent and AEs from randomization until post-study 5 to 7 days post-final study drug dose
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from AstraZeneca will be obtained and a draft manuscript will be submitted to AstraZeneca for scrutiny and comment. The choice of conduit will be mutually agreed on by the Principal Investigator and AstraZeneca.
- Publication restrictions are in place
Restriction type: OTHER