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Trial record 80 of 112 for:    EPLERENONE

A Study to Assess the Pharmacodynamic Effect of Single Doses of AZD9977 in Healthy Male Subjects

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ClinicalTrials.gov Identifier: NCT02532998
Recruitment Status : Completed
First Posted : August 26, 2015
Results First Posted : March 29, 2017
Last Update Posted : March 29, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Single (Participant);   Primary Purpose: Basic Science
Conditions Pharmacodynamics
Healthy Subjects
Interventions Drug: AZD9977 oral suspension
Drug: AZD9977 placebo oral suspension
Drug: Fludrocortisone, tablets
Drug: Eplerenone, tablets
Enrollment 40
Recruitment Details This study was conducted at PAREXEL Early Phase Clinical Unit London, United Kingdom
Pre-assignment Details 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.
Arm/Group Title All Particpants
Hide Arm/Group Description Twenty three healthy male participants aged 18 to 50 years who satisfied all the study inclusion criteria were included in the study
Period Title: Overall Study
Started 23
Completed 23
Not Completed 0
Arm/Group Title All Particpants
Hide Arm/Group Description Twenty three healthy male participants aged 18 to 50 years who satisfied all the study inclusion criteria were included in the study
Overall Number of Baseline Participants 23
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants
36  (8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
Female
0
   0.0%
Male
23
 100.0%
1.Primary Outcome
Title Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977.
Hide Description

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.

Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment C Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: sodium/potassium ratio
-0.545  (1.19) 0.694  (1.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment C, Treatment D
Comments Statistical analysis of urinary sodium/potassium ratio between Treatment C and Treatment D.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method mixed linear model
Comments Analyses done using mixed linear model involving fixed effect, random effect, and a covariate.
Method of Estimation Estimation Parameter Treatment differences
Estimated Value -1.258
Confidence Interval (2-Sided) 90%
-1.721 to 0.7945
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Observed Maximum Concentration (Cmax) of AZD9977
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment D Treatment B
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Overall Number of Participants Analyzed 23 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
6238
(16.7%)
5816
(22.2%)
3.Secondary Outcome
Title Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment D Treatment B
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Overall Number of Participants Analyzed 22 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*nmol/L
21060
(18.4%)
19120
(23.9%)
4.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC[0-t]) of AZD9977.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment D Treatment B
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Overall Number of Participants Analyzed 23 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*nmol/L
19970
(20.3%)
18520
(23.6%)
5.Secondary Outcome
Title Time to Reach Maximum Concentration (Tmax) of AZD9977.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment D Treatment B
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Overall Number of Participants Analyzed 23 23
Median (Full Range)
Unit of Measure: h
0.52
(0.48 to 1.02)
0.50
(0.48 to 2.50)
6.Secondary Outcome
Title Terminal Half-life (t½λz) of AZD9977.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment D Treatment B
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Overall Number of Participants Analyzed 22 21
Mean (Standard Deviation)
Unit of Measure: h
6.753  (2.322) 6.726  (1.719)
7.Secondary Outcome
Title Apparent Clearance (CL/F) of AZD9977.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment D Treatment B
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Overall Number of Participants Analyzed 22 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
23.78
(18.4%)
26.20
(23.9%)
8.Secondary Outcome
Title Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment B Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 21 22
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
246.7
(42.4%)
220.4
(34.3%)
9.Secondary Outcome
Title Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment C Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 23 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
49.11
(19.2%)
44.77
(19.3%)
10.Secondary Outcome
Title Apparent Clearance (CL/F) of Eplerenone.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment C Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 23 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/h
10.87
(34.4%)
9.360
(35.9%)
11.Secondary Outcome
Title Terminal Half-life (t½λz) of Eplerenone.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment C Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: h
3.232  (0.8305) 3.419  (0.8843)
12.Secondary Outcome
Title Time to Reach Maximum Concentration (Tmax) of Eplerenone.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment C Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 23 23
Median (Full Range)
Unit of Measure: h
1.98
(0.48 to 3.98)
2.00
(0.97 to 3.98)
13.Secondary Outcome
Title Observed Maximum Concentration (Cmax) of Eplerenone.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment C Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 23 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1557
(26.1%)
1729
(23.2%)
14.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC(0-t)) of Eplerenone.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment C Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 23 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
9035
(33.9%)
10510
(34.6%)
15.Secondary Outcome
Title Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone.
Hide Description 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
Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment C Treatment D
Hide Arm/Group Description:
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Participants received fludrocortisone + eplerenone + AZD9977
Overall Number of Participants Analyzed 23 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
9199
(34.4%)
10680
(35.9%)
16.Secondary Outcome
Title Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in AZD9977 Treatment With Placebo Versus Treatment With AZD9977.
Hide Description

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.

Time Frame From 2 hours post dose to 8 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + AZD9977
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: sodium/potassium ratio
-4.09  (2.11) -0.694  (1.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments Statistical analysis of urinary sodium/potassium ratio between Treatment A and Treatment B.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method mixed linear model
Comments Analyses done using mixed linear model involving fixed effect, random effect, and a covariate.
Method of Estimation Estimation Parameter Treatment differences
Estimated Value 3.409
Confidence Interval (2-Sided) 90%
2.946 to 3.872
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Number of Participants With Clinically Significant Blood Pressure Values.
Hide Description

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.
Time Frame From screening to post-study visit, up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
18.Secondary Outcome
Title Number of Participants With Clinically Significant Pulse Rate.
Hide Description

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)

Time Frame From screening to post-study visit, up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
19.Secondary Outcome
Title Number of Participants With Clinically Significant Electrocardiogram.
Hide Description

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.

Time Frame From screening to post-study visit, up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
20.Secondary Outcome
Title Number of Participants With Clinically Significant Physical Examination Values.
Hide Description

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).

Time Frame From screening to post-study visit, up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
21.Secondary Outcome
Title Number of Participants With Clinically Significant Safety Laboratory Tests Values.
Hide Description 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.
Time Frame From screening to post-study visit, up to 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Measure Type: Number
Unit of Measure: Participants
0 0 0 0
22.Secondary Outcome
Title Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval.
Hide Description

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.

Time Frame From 0 to 8 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Mean (Standard Deviation)
Unit of Measure: % value
0 to 2 hours 0.34  (0.18) 0.33  (0.19) 0.32  (0.09) 0.33  (0.20)
2 to 4 hours 0.22  (0.15) 0.48  (0.21) 0.35  (0.12) 0.37  (0.17)
4 to 6 hours 0.15  (0.12) 0.58  (0.19) 0.36  (0.13) 0.38  (0.14)
6 to 8 hours 0.16  (0.15) 0.66  (0.23) 0.36  (0.16) 0.48  (0.23)
23.Secondary Outcome
Title Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
Hide Description

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.

Time Frame From 0 to 24 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Mean (Standard Deviation)
Unit of Measure: mmol
0 to 2 hours 7  (3) 8  (6) 7  (3) 7  (4)
2 to 4 hours 12  (6) 17  (7) 15  (5) 15  (7)
4 to 6 hours 15  (8) 31  (12) 23  (8) 23  (8)
6 to 8 hours 19  (10) 46  (14) 32  (10) 34  (10)
8 to 10 hours 23  (12) 63  (17) 39  (12) 47  (14)
10 to 12 hours 28  (14) 74  (19) 46  (13) 55  (16)
12 to 14 hours 32  (17) 82  (22) 51  (14) 62  (19)
14 to 16 hours 36  (18) 87  (23) 54  (15) 67  (21)
16 to 24 hours 46  (23) 103  (29) 66  (19) 79  (24)
24.Secondary Outcome
Title Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval.
Hide Description

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

Time Frame From 0 to 8 hours post dosing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Mean (Standard Deviation)
Unit of Measure: % value
0 to 2 hours 21.72  (6.49) 22.19  (3.96) 21.14  (5.74) 21.66  (5.40)
2 to 4 hours 22.26  (4.22) 20.30  (4.45) 18.95  (2.78) 21.15  (5.25)
4 to 6 hours 14.60  (3.19) 12.49  (3.04) 12.12  (3.03) 12.48  (3.13)
6 to 8 hours 18.08  (4.64) 13.35  (5.60) 13.34  (4.56) 13.48  (3.55)
25.Secondary Outcome
Title Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
Hide Description

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.

Time Frame From 0 to 24 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Mean (Standard Deviation)
Unit of Measure: mmol
0 to 2 hours 13.6  (5.6) 14.5  (3.1) 14.0  (5.8) 13.7  (4.2)
2 to 4 hours 29.0  (9.4) 26.7  (5.7) 27.1  (7.7) 27.4  (7.6)
4 to 6 hours 38.3  (11.1) 35.2  (6.8) 35.5  (8.8) 35.9  (9.2)
6 to 8 hours 49.9  (13.3) 44.4  (8.7) 44.6  (10.4) 45.1  (10.7)
8 to 10 hours 61.4  (14.7) 54.4  (10.2) 53.8  (11.0) 54.9  (11.0)
10 to 12 hours 71.1  (15.7) 62.1  (12.2) 63.3  (11.4) 64.0  (12.4)
12 to 14 hours 80.7  (17.5) 71.3  (15) 72.5  (13.1) 73.5  (12.6)
14 to 16 hours 87.7  (17.4) 77.5  (15.1) 79.2  (13.2) 79.7  (12.9)
16 to 24 hours 101.8  (17.7) 92.1  (13) 94.4  (15.5) 95.4  (12.0)
26.Secondary Outcome
Title Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
Hide Description

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.

Time Frame From 8 hours before dosing until 24 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Mean (Standard Deviation)
Unit of Measure: mL
-8 to -2 hours 321.4  (208.3) 309.3  (182.5) 284.5  (186.4) 294.9  (130.3)
-2 to 0 hour 303.5  (111.7) 288.6  (99.3) 274.3  (113.7) 284.5  (90.2)
0 to 2 hour 307.4  (78.4) 320.2  (102.6) 305.0  (89.5) 298.8  (68.9)
2 to 4 hour 272.2  (105.0) 236.1  (80.1) 245.6  (63.2) 272.6  (85.8)
4 to 6 hours 178.8  (93.8) 246.0  (115.7) 229.9  (147.7) 202.2  (99.5)
6 to 8 hours 216.6  (99.3) 115.7  (121.6) 273.6  (96.6) 291.5  (135.5)
8 to 10 hours 266.0  (125.4) 326.6  (111.7) 246.6  (103.9) 300.2  (121.1)
10 to 12 hours 337.1  (132.0) 361.9  (149.0) 309.0  (137.4) 324.5  (143.6)
12 to 14 hours 280.2  (131.0) 300.7  (141.8) 306.0  (125.4) 306.3  (152.2)
14 to 16 hours 357.3  (124.8) 345.9  (129.0) 326.5  (115.3) 354.2  (138.6)
16 to 24 hours 296.0  (184.1) 302.8  (181.1) 292.2  (164.8) 290.6  (90.2)
27.Secondary Outcome
Title Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
Hide Description

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

Time Frame From 8 hours before dosing until 24 hours after dosing
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment D Treatment B Treatment C
Hide Arm/Group Description:
Participants received fludrocortisone + AZD9977 Placebo
Participants received fludrocortisone + eplerenone + AZD9977
Participants received fludrocortisone + AZD9977
Participants received fludrocortisone + eplerenone + AZD9977 Placebo.
Overall Number of Participants Analyzed 23 23 23 23
Mean (Standard Deviation)
Unit of Measure: mL
0 to 2 hour 307.4  (78.4) 320.2  (102.6) 305.0  (89.5) 298.8  (68.9)
2 to 4 hour 579.5  (127.2) 556.3  (126.1) 550.7  (109.2) 571.4  (128.3)
4 to 6 hours 758.3  (186.3) 802.2  (189.7) 780.6  (204.6) 773.6  (184.1)
6 to 8 hours 974.9  (235.6) 1099.0  (199.1) 1054.2  (201.4) 1065.1  (261.1)
8 to 10 hours 1242.2  (288.9) 1425.2  (235.6) 1300.8  (192.6) 1365.3  (261.1)
10 to 12 hours 1574.4  (329.0) 1791.7  (283.6) 1609.8  (264.2) 1689.8  (300.9)
12 to 14 hours 1865.1  (378.9) 2091.7  (354.6) 1915.8  (264.2) 1996.1  (330.7)
14 to 16 hours 2221.0  (340.7) 2435.7  (304.4) 2242.3  (233.3) 2350.3  (316.6)
16 to 24 hours 2506.6  (388.6) 2741.2  (293.9) 2534.5  (236.3) 2640.9  (347.5)
Time Frame 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
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment A Treatment B Treatment C Treatment D
Hide Arm/Group Description Participants received fludrocortisone + AZD9977 Placebo Participants received fludrocortisone + AZD9977 Participants received fludrocortisone + eplerenone + AZD9977 Placebo. Participants received fludrocortisone + eplerenone + AZD9977
All-Cause Mortality
Treatment A Treatment B Treatment C Treatment D
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment A Treatment B Treatment C Treatment D
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/23 (0.00%)      0/23 (0.00%)      0/23 (0.00%)      0/23 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment A Treatment B Treatment C Treatment D
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/23 (8.70%)      3/23 (13.04%)      2/23 (8.70%)      4/23 (17.39%)    
Eye disorders         
Ocular hyperemia   0/23 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0
Gastrointestinal disorders         
Abdominal distention   0/23 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0
Abdominal pain   0/23 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0
Flatulence   0/23 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0
General disorders         
Pyrexia   0/23 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1
Infections and infestations         
Nasopharyngitis   1/23 (4.35%)  1 1/23 (4.35%)  1 1/23 (4.35%)  1 0/23 (0.00%)  0
Injury, poisoning and procedural complications         
Splinter   0/23 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1
Nervous system disorders         
Headache   1/23 (4.35%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 2/23 (8.70%)  2
Dizziness   0/23 (0.00%)  0 1/23 (4.35%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Rhinorrhea   0/23 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1
Sneezing   1/23 (4.35%)  1 0/23 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0
Skin and subcutaneous tissue disorders         
Skin irritation   0/23 (0.00%)  0 0/23 (0.00%)  0 0/23 (0.00%)  0 1/23 (4.35%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: AZD9977 Global Clinical Leader
Organization: AstraZeneca AB
Phone: +46317761000
EMail: ClinicalTrialTransparency@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02532998     History of Changes
Other Study ID Numbers: D6400C00004
2015-002224-11 ( EudraCT Number )
First Submitted: August 24, 2015
First Posted: August 26, 2015
Results First Submitted: December 1, 2016
Results First Posted: March 29, 2017
Last Update Posted: March 29, 2017