A Study to Assess the Pharmacodynamic Effect of Single Doses of AZD9977 in Healthy Male Subjects
Condition: Pharmacodynamics; Healthy Subjects
Intervention: AZD9977 oral suspension; AZD9977 placebo oral suspension; Fludrocortisone, tablets; Eplerenone, tablets
Intervention description: AZD9977 oral suspension, single dose; oral suspension, single dose; 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); 100 mg (2 x 50 mg tablets) single dose, may be modified based on emerging data (will not exceed 500 mg per treatment period)
Intervention MeSH terms: Fludrocortisone; Eplerenone
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Enrollment: 40.0
Sex: Male
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacodynamics; AZD9977; Safety; Tolerability; Pharmacokinetics; Eplerenone; Fludrocortisone

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
    

Eligibility 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.