Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 80 of 112 for:    EPLERENONE

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: 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

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

Condition or disease Intervention/treatment Phase
Pharmacodynamics Healthy Subjects Drug: AZD9977 oral suspension Drug: AZD9977 placebo oral suspension Drug: Fludrocortisone, tablets Drug: Eplerenone, tablets Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: A Phase I, Randomized, Single-Blind, Crossover Study to Assess the Pharmacodynamics of AZD9977 Following Single-Dose Administration to Healthy Male Subjects
Study Start Date : September 2015
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Potassium

Arm Intervention/treatment
Experimental: Treatment Sequence 1
Period 1: fludrocortisone + eplerenone + AZD9977 Period 2: fludrocortisone + eplerenone + AZD9977 Placebo Period 3: fludrocortisone + AZD9977 Placebo Period 4: fludrocortisone + AZD9977 Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment
Drug: AZD9977 oral suspension
AZD9977 oral suspension, single dose

Drug: AZD9977 placebo oral suspension
oral suspension, single dose

Drug: Fludrocortisone, 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)

Drug: Eplerenone, 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)

Experimental: Treatment Sequence 2
Period 1: fludrocortisone + AZD9977 Placebo Period 2: fludrocortisone + eplerenone + AZD9977 Period 3: fludrocortisone + AZD9977 Period 4: fludrocortisone + eplerenone + AZD9977 Placebo Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment
Drug: AZD9977 oral suspension
AZD9977 oral suspension, single dose

Drug: AZD9977 placebo oral suspension
oral suspension, single dose

Drug: Fludrocortisone, 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)

Drug: Eplerenone, 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)

Experimental: Treatment Sequence 3
Period 1: fludrocortisone + AZD9977 Period 2: fludrocortisone + AZD9977 Placebo Period 3: fludrocortisone + eplerenone + AZD9977 Placebo Period 4: fludrocortisone + eplerenone + AZD9977 Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment
Drug: AZD9977 oral suspension
AZD9977 oral suspension, single dose

Drug: AZD9977 placebo oral suspension
oral suspension, single dose

Drug: Fludrocortisone, 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)

Drug: Eplerenone, 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)

Experimental: Treatment Sequence 4
Period 1: fludrocortisone + eplerenone + AZD9977 Placebo Period 2: fludrocortisone + eplerenone + AZD9977 Period 3: fludrocortisone + AZD9977 Period 4: fludrocortisone + AZD9977 Placebo Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment
Drug: AZD9977 oral suspension
AZD9977 oral suspension, single dose

Drug: AZD9977 placebo oral suspension
oral suspension, single dose

Drug: Fludrocortisone, 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)

Drug: Eplerenone, 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)

Experimental: Treatment Sequence 5
Period 1: fludrocortisone + eplerenone + AZD9977 Period 2: fludrocortisone + eplerenone + AZD9977 Placebo Period 3: fludrocortisone + AZD9977 Placebo Period 4: fludrocortisone + AZD9977 Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment
Drug: AZD9977 oral suspension
AZD9977 oral suspension, single dose

Drug: AZD9977 placebo oral suspension
oral suspension, single dose

Drug: Fludrocortisone, 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)

Drug: Eplerenone, 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)

Experimental: Treatment Sequence 6
Period 1: fludrocortisone + AZD9977 Placebo Period 2: fludrocortisone + eplerenone + AZD9977 Period 3: fludrocortisone + AZD9977 Period 4: fludrocortisone + eplerenone + AZD9977 Placebo Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment
Drug: AZD9977 oral suspension
AZD9977 oral suspension, single dose

Drug: AZD9977 placebo oral suspension
oral suspension, single dose

Drug: Fludrocortisone, 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)

Drug: Eplerenone, 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)

Experimental: Treatment Sequence 7
Period 1: fludrocortisone + AZD9977 Period 2: fludrocortisone + AZD9977 Placebo Period 3: fludrocortisone + eplerenone + AZD9977 Placebo Period 4: fludrocortisone + eplerenone + AZD9977 Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment
Drug: AZD9977 oral suspension
AZD9977 oral suspension, single dose

Drug: AZD9977 placebo oral suspension
oral suspension, single dose

Drug: Fludrocortisone, 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)

Drug: Eplerenone, 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)

Experimental: Treatment Sequence 8
Period 1: fludrocortisone + eplerenone + AZD9977 Placebo Period 2: fludrocortisone + AZD9977 Period 3: fludrocortisone + eplerenone + AZD9977 Period 4: fludrocortisone + AZD9977 Placebo Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment
Drug: AZD9977 oral suspension
AZD9977 oral suspension, single dose

Drug: AZD9977 placebo oral suspension
oral suspension, single dose

Drug: Fludrocortisone, 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)

Drug: Eplerenone, 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)




Primary Outcome Measures :
  1. Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977. [ Time Frame: 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 Outcome Measures :
  1. Observed Maximum Concentration (Cmax) of AZD9977 [ Time Frame: 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

  2. Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977. [ Time Frame: 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

  3. Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC[0-t]) of AZD9977. [ Time Frame: 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

  4. Time to Reach Maximum Concentration (Tmax) of AZD9977. [ Time Frame: 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

  5. Terminal Half-life (t½λz) of AZD9977. [ Time Frame: 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

  6. Apparent Clearance (CL/F) of AZD9977. [ Time Frame: 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

  7. Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977. [ Time Frame: 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

  8. Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone. [ Time Frame: 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

  9. Apparent Clearance (CL/F) of Eplerenone. [ Time Frame: 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

  10. Terminal Half-life (t½λz) of Eplerenone. [ Time Frame: 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

  11. Time to Reach Maximum Concentration (Tmax) of Eplerenone. [ Time Frame: 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

  12. Observed Maximum Concentration (Cmax) of Eplerenone. [ Time Frame: 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

  13. Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC(0-t)) of Eplerenone. [ Time Frame: 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

  14. Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone. [ Time Frame: 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

  15. Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in AZD9977 Treatment With Placebo Versus Treatment With AZD9977. [ Time Frame: 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.


  16. Number of Participants With Clinically Significant Blood Pressure Values. [ Time Frame: 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.

  17. Number of Participants With Clinically Significant Pulse Rate. [ Time Frame: 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)


  18. Number of Participants With Clinically Significant Electrocardiogram. [ Time Frame: 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.


  19. Number of Participants With Clinically Significant Physical Examination Values. [ Time Frame: 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).


  20. Number of Participants With Clinically Significant Safety Laboratory Tests Values. [ Time Frame: 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.

  21. Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval. [ Time Frame: 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.


  22. Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals. [ Time Frame: 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.


  23. Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval. [ Time Frame: 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


  24. Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals [ Time Frame: 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.


  25. Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval. [ Time Frame: 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.


  26. Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals [ Time Frame: 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




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02532998


Locations
Layout table for location information
United Kingdom
Research Site
Harrow, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: Muna Albayaty, MBChB, MSc, MFPM PAREXEL Early Phase Clinical Unit London

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 Posted: August 26, 2015    Key Record Dates
Results First Posted: March 29, 2017
Last Update Posted: March 29, 2017
Last Verified: February 2017
Keywords provided by AstraZeneca:
Pharmacodynamics
AZD9977
Safety
Tolerability
Pharmacokinetics
Eplerenone
Fludrocortisone
Additional relevant MeSH terms:
Layout table for MeSH terms
Eplerenone
Fludrocortisone
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Antihypertensive Agents
Anti-Inflammatory Agents