Healthy Subjects, Pharmacodynamics
Conditions
Keywords
Pharmacodynamics, AZD9977, Safety, Tolerability, Pharmacokinetics, Eplerenone, Fludrocortisone
Brief summary
This is a Phase I, Randomized, Single-Blind, Crossover Study to Assess the Pharmacodynamics of AZD9977 following Single-Dose administration to healthy male subjects
Detailed description
This study will be a phase I study to assess the pharmacodynamics of AZD9977 following single-dose administration to healthy male subjects. It is a single-blind (with regards to AZD9977 and AZD9977 Placebo), randomized, four-treatment, four-period crossover design, with a potential 5th and 6th randomized cross-over treatment period. In this study eplerenone is used as a positive control and fludrocortisone will be used as a challenge agent. In addition the safety, tolerability and pharmacokinetics will be assessed.
Interventions
DRUGAZD9977 oral suspension
AZD9977 oral suspension, single dose
DRUGAZD9977 placebo oral suspension
oral suspension, single dose
DRUGFludrocortisone, tablets
Loading dose of 0.5 mg and maintenance doses of 0.1 mg every second hour up to a total dose of 1.0 mg per treatment period (may be modified to up to 1.3 mg based on emerging data)
DRUGEplerenone, tablets
100 mg (2 x 50 mg tablets) single dose, may be modified based on emerging data (will not exceed 500 mg per treatment period)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated written informed consent prior to any study specific procedures. 2. Healthy male subjects aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture. 3. Male subjects must accept to comply with the restrictions for sexual activity provided to them. 4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive. 5. Optional: Provision of signed and dated written informed consent for genetic research. Note: Participation in exploratory biomarker research is mandatory. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol. 6. Able to understand, read and speak the English language.
Exclusion criteria
1. History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influences the results or the potential subject's ability to participate in the study. 2. History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of first dosing with investigational medicinal product (IMP). 4. Any clinically significant abnormalities in hematology, clinical chemistry or urinalysis results, as judged by the investigator. 5. Abnormal findings in vital signs, after 10 minutes resting in the supine position, defined as any of the following: * Systolic blood pressure (SBP) \< 90 mmHg or ≥ 140 mmHg * Diastolic blood pressure (DBP) \< 50 mmHg or ≥ 90 mmHg * Pulse \< 45 or \> 85 beats per minute (bpm) 6. Any clinically significant abnormalities on the 12-lead electrocardiogram (ECG), as judged by the investigator. 7. Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibodies. 8. Known or suspected history of drug abuse, as judged by the investigator. 9. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of first dosing. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest. Note: Subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded. 10. Plasma donation within one month of screening or any blood donation/blood loss \> 500 mL during the 3 months prior to screening. 11. History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977. 12. Current smokers or those who have smoked or used nicotine products within the previous 3 months. 13. Positive screen for drugs of abuse, alcohol or cotinine at screening or for each admission to the study center. 14. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to first dosing. 15. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during 2 weeks prior to first dosing, or longer if the medication has a long half-life. 16. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol, as judged by the investigator. 17. Involvement of any AstraZeneca or study site employee or their close relatives. 18. Subjects who previously received AZD9977. 19. Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements. 20. Known allergy to eplerenone or fludrocortisone or any of the constituents (including lactose, which is a constituent of Florinef™). 21. History of galactose intolerance. 22. Any infections or at risk of infection (surgery, trauma, or significant infection) within 90 days of screening, or history of skin abscesses within 90 days of screening. 23. Presence, history or family history of long QT syndrome, hypokalemia, hyperkalemia or Torsades de Pointes. 24. Serum potassium \< 3.5 mmol/L or ≥ 5.0 mmol/L at screening or for each admission to the study center. 25. Presence or history of active peptic ulcer. 26. History of any psychiatric disorder (including affective, psychotic, behavioral, irritability, anxiety, sleep disturbances and cognitive disorders) which required specialist psychiatric review. 27. Excessive intake of caffeine containing drinks or food (e.g., coffee, tea and chocolate) as judged by the investigator. 28. Subjects who are vegans or have medical dietary restrictions (vegetarians may be included in the study). 29. Subjects who cannot communicate reliably with the investigator. 30. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order. 31. In addition, any of the following is regarded as a criterion for exclusion from the genetic research: * Previous bone marrow transplant. * Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977. | From 2 hours post dose to 8 hours post dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Observed Maximum Concentration (Cmax) of AZD9977 | From 2 hours post dose to 8 hours post dose | 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 |
| Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977. | From 2 hours post dose to 8 hours post dose | 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 |
| Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC[0-t]) of AZD9977. | From 2 hours post dose to 8 hours post dose | 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 to Reach Maximum Concentration (Tmax) of AZD9977. | From 2 hours post dose to 8 hours post dose | 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 |
| Terminal Half-life (t½λz) of AZD9977. | From 2 hours post dose to 8 hours post dose | 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 |
| Apparent Clearance (CL/F) of AZD9977. | From 2 hours post dose to 8 hours post dose | 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 |
| Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977. | From 2 hours post dose to 8 hours post dose | 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 |
| Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone. | From 2 hours post dose to 8 hours post dose | 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 |
| Apparent Clearance (CL/F) of Eplerenone. | From 2 hours post dose to 8 hours post dose | 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 |
| Terminal Half-life (t½λz) of Eplerenone. | From 2 hours post dose to 8 hours post dose | 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 to Reach Maximum Concentration (Tmax) of Eplerenone. | From 2 hours post dose to 8 hours post dose | 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 |
| Observed Maximum Concentration (Cmax) of Eplerenone. | From 2 hours post dose to 8 hours post dose | 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 |
| Number of Participants With Clinically Significant Blood Pressure Values. | From screening to post-study visit, up to 10 weeks | 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. |
| Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone. | From 2 hours post dose to 8 hours post dose | 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 |
| Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in AZD9977 Treatment With Placebo Versus Treatment With AZD9977. | From 2 hours post dose to 8 hours post dose | 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. |
| Number of Participants With Clinically Significant Pulse Rate. | From screening to post-study visit, up to 10 weeks | 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) |
| Number of Participants With Clinically Significant Electrocardiogram. | From screening to post-study visit, up to 10 weeks | 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. |
| Number of Participants With Clinically Significant Physical Examination Values. | From screening to post-study visit, up to 10 weeks | 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). |
| Number of Participants With Clinically Significant Safety Laboratory Tests Values. | From screening to post-study visit, up to 10 weeks | 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. |
| Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | From 0 to 8 hours after dosing | 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. |
| Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | From 0 to 24 hours after dosing | 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. |
| Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | From 0 to 8 hours post dosing | 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 |
| Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | From 0 to 24 hours after dosing | 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. |
| Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | From 8 hours before dosing until 24 hours after dosing | 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. |
| Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | From 8 hours before dosing until 24 hours after dosing | 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 |
| Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC(0-t)) of Eplerenone. | From 2 hours post dose to 8 hours post dose | 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 |
Countries
United Kingdom
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| All Particpants Twenty three healthy male participants aged 18 to 50 years who satisfied all the study inclusion criteria were included in the study | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | All Particpants |
|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 23 | 3 / 23 | 2 / 23 | 4 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977.
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | 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 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977. | 0.694 sodium/potassium ratio | Standard Deviation 1.18 |
Comparison: Statistical analysis of urinary sodium/potassium ratio between Treatment C and Treatment D.90% CI: [-1.721, 0.7945]mixed linear model
Secondary
Apparent Clearance (CL/F) of AZD9977.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Apparent Clearance (CL/F) of AZD9977. | 23.78 L/h | Geometric Coefficient of Variation 18.4 |
| Treatment D | Apparent Clearance (CL/F) of AZD9977. | 26.20 L/h | Geometric Coefficient of Variation 23.9 |
Secondary
Apparent Clearance (CL/F) of Eplerenone.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Apparent Clearance (CL/F) of Eplerenone. | 10.87 L/h | Geometric Coefficient of Variation 34.4 |
| Treatment D | Apparent Clearance (CL/F) of Eplerenone. | 9.360 L/h | Geometric Coefficient of Variation 35.9 |
Secondary
Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977. | 246.7 L | Geometric Coefficient of Variation 42.4 |
| Treatment D | Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977. | 220.4 L | Geometric Coefficient of Variation 34.3 |
Secondary
Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone. | 49.11 L | Geometric Coefficient of Variation 19.2 |
| Treatment D | Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone. | 44.77 L | Geometric Coefficient of Variation 19.3 |
Secondary
Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977. | 21060 h*nmol/L | Geometric Coefficient of Variation 18.4 |
| Treatment D | Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977. | 19120 h*nmol/L | Geometric Coefficient of Variation 23.9 |
Secondary
Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone. | 9199 h*ng/mL | Geometric Coefficient of Variation 34.4 |
| Treatment D | Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone. | 10680 h*ng/mL | Geometric Coefficient of Variation 35.9 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC[0-t]) of AZD9977.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | 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 |
| Treatment D | Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC[0-t]) of AZD9977. | 18520 h*nmol/L | Geometric Coefficient of Variation 23.6 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC(0-t)) of Eplerenone.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | 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 |
| Treatment D | Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC(0-t)) of Eplerenone. | 10510 h*ng/mL | Geometric Coefficient of Variation 34.6 |
Secondary
Number of Participants With Clinically Significant Blood Pressure Values.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Treatment C | Number of Participants With Clinically Significant Blood Pressure Values. | 0 Participants |
| Treatment D | Number of Participants With Clinically Significant Blood Pressure Values. | 0 Participants |
| Treatment B | Number of Participants With Clinically Significant Blood Pressure Values. | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Blood Pressure Values. | 0 Participants |
Secondary
Number of Participants With Clinically Significant Electrocardiogram.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Treatment C | Number of Participants With Clinically Significant Electrocardiogram. | 0 Participants |
| Treatment D | Number of Participants With Clinically Significant Electrocardiogram. | 0 Participants |
| Treatment B | Number of Participants With Clinically Significant Electrocardiogram. | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Electrocardiogram. | 0 Participants |
Secondary
Number of Participants With Clinically Significant Physical Examination Values.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Treatment C | Number of Participants With Clinically Significant Physical Examination Values. | 0 Participants |
| Treatment D | Number of Participants With Clinically Significant Physical Examination Values. | 0 Participants |
| Treatment B | Number of Participants With Clinically Significant Physical Examination Values. | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Physical Examination Values. | 0 Participants |
Secondary
Number of Participants With Clinically Significant Pulse Rate.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Treatment C | Number of Participants With Clinically Significant Pulse Rate. | 0 Participants |
| Treatment D | Number of Participants With Clinically Significant Pulse Rate. | 0 Participants |
| Treatment B | Number of Participants With Clinically Significant Pulse Rate. | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Pulse Rate. | 0 Participants |
Secondary
Number of Participants With Clinically Significant Safety Laboratory Tests Values.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Treatment C | Number of Participants With Clinically Significant Safety Laboratory Tests Values. | 0 Participants |
| Treatment D | Number of Participants With Clinically Significant Safety Laboratory Tests Values. | 0 Participants |
| Treatment B | Number of Participants With Clinically Significant Safety Laboratory Tests Values. | 0 Participants |
| Treatment C | Number of Participants With Clinically Significant Safety Laboratory Tests Values. | 0 Participants |
Secondary
Observed Maximum Concentration (Cmax) of AZD9977
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Observed Maximum Concentration (Cmax) of AZD9977 | 6238 nmol/L | Geometric Coefficient of Variation 16.7 |
| Treatment D | Observed Maximum Concentration (Cmax) of AZD9977 | 5816 nmol/L | Geometric Coefficient of Variation 22.2 |
Secondary
Observed Maximum Concentration (Cmax) of Eplerenone.
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Observed Maximum Concentration (Cmax) of Eplerenone. | 1557 ng/mL | Geometric Coefficient of Variation 26.1 |
| Treatment D | Observed Maximum Concentration (Cmax) of Eplerenone. | 1729 ng/mL | Geometric Coefficient of Variation 23.2 |
Secondary
Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 2 to 4 hours | 0.48 % value | Standard Deviation 0.21 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 4 to 6 hours | 0.58 % value | Standard Deviation 0.19 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 6 to 8 hours | 0.66 % value | Standard Deviation 0.23 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 0 to 2 hours | 0.33 % value | Standard Deviation 0.19 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 4 to 6 hours | 0.36 % value | Standard Deviation 0.13 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 2 to 4 hours | 0.35 % value | Standard Deviation 0.12 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 6 to 8 hours | 0.36 % value | Standard Deviation 0.16 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 0 to 2 hours | 0.32 % value | Standard Deviation 0.09 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 6 to 8 hours | 0.48 % value | Standard Deviation 0.23 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 2 to 4 hours | 0.37 % value | Standard Deviation 0.17 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 0 to 2 hours | 0.33 % value | Standard Deviation 0.2 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. | 4 to 6 hours | 0.38 % value | Standard Deviation 0.14 |
Secondary
Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 2 to 4 hours | 20.30 % value | Standard Deviation 4.45 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 4 to 6 hours | 12.49 % value | Standard Deviation 3.04 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 6 to 8 hours | 13.35 % value | Standard Deviation 5.6 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 0 to 2 hours | 22.19 % value | Standard Deviation 3.96 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 4 to 6 hours | 12.12 % value | Standard Deviation 3.03 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 2 to 4 hours | 18.95 % value | Standard Deviation 2.78 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 6 to 8 hours | 13.34 % value | Standard Deviation 4.56 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 0 to 2 hours | 21.14 % value | Standard Deviation 5.74 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 6 to 8 hours | 13.48 % value | Standard Deviation 3.55 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 2 to 4 hours | 21.15 % value | Standard Deviation 5.25 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 0 to 2 hours | 21.66 % value | Standard Deviation 5.4 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. | 4 to 6 hours | 12.48 % value | Standard Deviation 3.13 |
Secondary
Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in AZD9977 Treatment With Placebo Versus Treatment With AZD9977.
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | 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 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in AZD9977 Treatment With Placebo Versus Treatment With AZD9977. | -0.694 sodium/potassium ratio | Standard Deviation 1.27 |
Comparison: Statistical analysis of urinary sodium/potassium ratio between Treatment A and Treatment B.90% CI: [2.946, 3.872]mixed linear model
Secondary
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 8 to 10 hours | 63 mmol | Standard Deviation 17 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 12 to 14 hours | 82 mmol | Standard Deviation 22 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 10 to 12 hours | 74 mmol | Standard Deviation 19 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 2 to 4 hours | 17 mmol | Standard Deviation 7 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 0 to 2 hours | 8 mmol | Standard Deviation 6 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 4 to 6 hours | 31 mmol | Standard Deviation 12 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 16 to 24 hours | 103 mmol | Standard Deviation 29 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 14 to 16 hours | 87 mmol | Standard Deviation 23 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 6 to 8 hours | 46 mmol | Standard Deviation 14 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 8 to 10 hours | 39 mmol | Standard Deviation 12 |
| Treatment B | 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 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 2 to 4 hours | 15 mmol | Standard Deviation 5 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 4 to 6 hours | 23 mmol | Standard Deviation 8 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 6 to 8 hours | 32 mmol | Standard Deviation 10 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 10 to 12 hours | 46 mmol | Standard Deviation 13 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 12 to 14 hours | 51 mmol | Standard Deviation 14 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 14 to 16 hours | 54 mmol | Standard Deviation 15 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 16 to 24 hours | 66 mmol | Standard Deviation 19 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 12 to 14 hours | 62 mmol | Standard Deviation 19 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 6 to 8 hours | 34 mmol | Standard Deviation 10 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 4 to 6 hours | 23 mmol | Standard Deviation 8 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 16 to 24 hours | 79 mmol | Standard Deviation 24 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 14 to 16 hours | 67 mmol | Standard Deviation 21 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 2 to 4 hours | 15 mmol | Standard Deviation 7 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 10 to 12 hours | 55 mmol | Standard Deviation 16 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. | 8 to 10 hours | 47 mmol | Standard Deviation 14 |
| Treatment C | 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 4 |
Secondary
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 6 to 8 hours | 216.6 mL | Standard Deviation 99.3 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 4 to 6 hours | 178.8 mL | Standard Deviation 93.8 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 2 to 4 hour | 272.2 mL | Standard Deviation 105 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 16 to 24 hours | 296.0 mL | Standard Deviation 184.1 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 14 to 16 hours | 357.3 mL | Standard Deviation 124.8 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | -2 to 0 hour | 303.5 mL | Standard Deviation 111.7 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | -8 to -2 hours | 321.4 mL | Standard Deviation 208.3 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 12 to 14 hours | 280.2 mL | Standard Deviation 131 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 10 to 12 hours | 337.1 mL | Standard Deviation 132 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 0 to 2 hour | 307.4 mL | Standard Deviation 78.4 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 8 to 10 hours | 266.0 mL | Standard Deviation 125.4 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 0 to 2 hour | 320.2 mL | Standard Deviation 102.6 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | -8 to -2 hours | 309.3 mL | Standard Deviation 182.5 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | -2 to 0 hour | 288.6 mL | Standard Deviation 99.3 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 2 to 4 hour | 236.1 mL | Standard Deviation 80.1 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 4 to 6 hours | 246.0 mL | Standard Deviation 115.7 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 6 to 8 hours | 115.7 mL | Standard Deviation 121.6 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 8 to 10 hours | 326.6 mL | Standard Deviation 111.7 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 10 to 12 hours | 361.9 mL | Standard Deviation 149 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 12 to 14 hours | 300.7 mL | Standard Deviation 141.8 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 14 to 16 hours | 345.9 mL | Standard Deviation 129 |
| Treatment D | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 16 to 24 hours | 302.8 mL | Standard Deviation 181.1 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 14 to 16 hours | 326.5 mL | Standard Deviation 115.3 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 6 to 8 hours | 273.6 mL | Standard Deviation 96.6 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 8 to 10 hours | 246.6 mL | Standard Deviation 103.9 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | -8 to -2 hours | 284.5 mL | Standard Deviation 186.4 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 10 to 12 hours | 309.0 mL | Standard Deviation 137.4 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | -2 to 0 hour | 274.3 mL | Standard Deviation 113.7 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 12 to 14 hours | 306.0 mL | Standard Deviation 125.4 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 2 to 4 hour | 245.6 mL | Standard Deviation 63.2 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 16 to 24 hours | 292.2 mL | Standard Deviation 164.8 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 4 to 6 hours | 229.9 mL | Standard Deviation 147.7 |
| Treatment B | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 0 to 2 hour | 305.0 mL | Standard Deviation 89.5 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 16 to 24 hours | 290.6 mL | Standard Deviation 90.2 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 0 to 2 hour | 298.8 mL | Standard Deviation 68.9 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 6 to 8 hours | 291.5 mL | Standard Deviation 135.5 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 14 to 16 hours | 354.2 mL | Standard Deviation 138.6 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 12 to 14 hours | 306.3 mL | Standard Deviation 152.2 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 8 to 10 hours | 300.2 mL | Standard Deviation 121.1 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | -2 to 0 hour | 284.5 mL | Standard Deviation 90.2 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | -8 to -2 hours | 294.9 mL | Standard Deviation 130.3 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 4 to 6 hours | 202.2 mL | Standard Deviation 99.5 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 10 to 12 hours | 324.5 mL | Standard Deviation 143.6 |
| Treatment C | Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. | 2 to 4 hour | 272.6 mL | Standard Deviation 85.8 |
Secondary
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 8 to 10 hours | 54.4 mmol | Standard Deviation 10.2 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 12 to 14 hours | 71.3 mmol | Standard Deviation 15 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 10 to 12 hours | 62.1 mmol | Standard Deviation 12.2 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 2 to 4 hours | 26.7 mmol | Standard Deviation 5.7 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 0 to 2 hours | 14.5 mmol | Standard Deviation 3.1 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 4 to 6 hours | 35.2 mmol | Standard Deviation 6.8 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 16 to 24 hours | 92.1 mmol | Standard Deviation 13 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 14 to 16 hours | 77.5 mmol | Standard Deviation 15.1 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 6 to 8 hours | 44.4 mmol | Standard Deviation 8.7 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 8 to 10 hours | 53.8 mmol | Standard Deviation 11 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 0 to 2 hours | 14.0 mmol | Standard Deviation 5.8 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 2 to 4 hours | 27.1 mmol | Standard Deviation 7.7 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 4 to 6 hours | 35.5 mmol | Standard Deviation 8.8 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 6 to 8 hours | 44.6 mmol | Standard Deviation 10.4 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 10 to 12 hours | 63.3 mmol | Standard Deviation 11.4 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 12 to 14 hours | 72.5 mmol | Standard Deviation 13.1 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 14 to 16 hours | 79.2 mmol | Standard Deviation 13.2 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 16 to 24 hours | 94.4 mmol | Standard Deviation 15.5 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 12 to 14 hours | 73.5 mmol | Standard Deviation 12.6 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 6 to 8 hours | 45.1 mmol | Standard Deviation 10.7 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 4 to 6 hours | 35.9 mmol | Standard Deviation 9.2 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 16 to 24 hours | 95.4 mmol | Standard Deviation 12 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 14 to 16 hours | 79.7 mmol | Standard Deviation 12.9 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 2 to 4 hours | 27.4 mmol | Standard Deviation 7.6 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 10 to 12 hours | 64.0 mmol | Standard Deviation 12.4 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 8 to 10 hours | 54.9 mmol | Standard Deviation 11 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals | 0 to 2 hours | 13.7 mmol | Standard Deviation 4.2 |
Secondary
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment C | 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 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 8 to 10 hours | 1425.2 mL | Standard Deviation 235.6 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 12 to 14 hours | 2091.7 mL | Standard Deviation 354.6 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 10 to 12 hours | 1791.7 mL | Standard Deviation 283.6 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 2 to 4 hour | 556.3 mL | Standard Deviation 126.1 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 0 to 2 hour | 320.2 mL | Standard Deviation 102.6 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 4 to 6 hours | 802.2 mL | Standard Deviation 189.7 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 16 to 24 hours | 2741.2 mL | Standard Deviation 293.9 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 14 to 16 hours | 2435.7 mL | Standard Deviation 304.4 |
| Treatment D | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 6 to 8 hours | 1099.0 mL | Standard Deviation 199.1 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 8 to 10 hours | 1300.8 mL | Standard Deviation 192.6 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 0 to 2 hour | 305.0 mL | Standard Deviation 89.5 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 2 to 4 hour | 550.7 mL | Standard Deviation 109.2 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 4 to 6 hours | 780.6 mL | Standard Deviation 204.6 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 6 to 8 hours | 1054.2 mL | Standard Deviation 201.4 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 10 to 12 hours | 1609.8 mL | Standard Deviation 264.2 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 12 to 14 hours | 1915.8 mL | Standard Deviation 264.2 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 14 to 16 hours | 2242.3 mL | Standard Deviation 233.3 |
| Treatment B | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 16 to 24 hours | 2534.5 mL | Standard Deviation 236.3 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 12 to 14 hours | 1996.1 mL | Standard Deviation 330.7 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 6 to 8 hours | 1065.1 mL | Standard Deviation 261.1 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 4 to 6 hours | 773.6 mL | Standard Deviation 184.1 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 16 to 24 hours | 2640.9 mL | Standard Deviation 347.5 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 14 to 16 hours | 2350.3 mL | Standard Deviation 316.6 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 2 to 4 hour | 571.4 mL | Standard Deviation 128.3 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 10 to 12 hours | 1689.8 mL | Standard Deviation 300.9 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 8 to 10 hours | 1365.3 mL | Standard Deviation 261.1 |
| Treatment C | Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals | 0 to 2 hour | 298.8 mL | Standard Deviation 68.9 |
Secondary
Terminal Half-life (t½λz) of AZD9977.
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Terminal Half-life (t½λz) of AZD9977. | 6.753 h | Standard Deviation 2.322 |
| Treatment D | Terminal Half-life (t½λz) of AZD9977. | 6.726 h | Standard Deviation 1.719 |
Secondary
Terminal Half-life (t½λz) of Eplerenone.
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment C | Terminal Half-life (t½λz) of Eplerenone. | 3.232 h | Standard Deviation 0.8305 |
| Treatment D | Terminal Half-life (t½λz) of Eplerenone. | 3.419 h | Standard Deviation 0.8843 |
Secondary
Time to Reach Maximum Concentration (Tmax) of AZD9977.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment C | Time to Reach Maximum Concentration (Tmax) of AZD9977. | 0.52 h |
| Treatment D | Time to Reach Maximum Concentration (Tmax) of AZD9977. | 0.50 h |
Secondary
Time to Reach Maximum Concentration (Tmax) of Eplerenone.
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment C | Time to Reach Maximum Concentration (Tmax) of Eplerenone. | 1.98 h |
| Treatment D | Time to Reach Maximum Concentration (Tmax) of Eplerenone. | 2.00 h |