A Study to Assess the Reaction of Body for Four Different Formulations of AZD9977 (Part A) and Influence of Food and Lower Dose of a Selected Formulation (Part B) in Healthy Male Subjects
Condition: Heart Failure
MeSH terms: Heart Failure
Study type: Interventional
Phase: Phase 1

Summary: 
      AZD9977 is an oral, selective mineralocorticoid receptor (MR) modulator. AZD9977 is a partial
      antagonist and partial agonist in reporter gene assays and has a different interaction
      pattern with the MR compared to eplerenone.

      This study will assess the pharmacokinetics (PK) of four different Formulations of AZD9977
      (Part A) and influence of food and lower dose of a selected formulation (Part B) in healthy
      male subjects.
    

Detailed description: 
      This study will be a randomized, open-label, single-centre crossover study in healthy male
      subjects. The study is divided into 2 parts, Part A and Part B. The subjects will participate
      in both Part A and Part B.

      Part A will be a 4-way cross-over study comparing the PK of AZD9977 as a reference capsule
      and 2 different capsule formulations and a tablet formulation under fasting conditions.

        -  Treatment A: Reference, AZD9977 capsule

        -  Treatment B: AZD9977 HDL capsule

        -  Treatment C: AZD9977 ODL capsule

        -  Treatment D: AZD9977 tablet In Part B, based on the interim results in Part A, 1 of the
           formulations will be selected and evaluated at the 300 mg dose level under fed
           conditions. The same formulation will also be evaluated under fasting conditions at a
           lower dose level (50 mg). The first dose tested in Part B will be the 50 mg (fasted)
           dose, followed by the 300 mg (fed) dose.

      In Part A, subjects will be resident from 1 day before dosing (Day -1 of Treatment Period 1)
      with AZD9977 until 48 hours post-final-dose (Day 3 of Treatment Period 4). Subjects will
      return to the unit for Part B at least 48 hours (and up to 5 weeks) after completion of Part
      A.

      In Part B, subjects will be resident from 1 day before dosing (Day -1 of Treatment Period 1)
      with AZD9977 until 48 hours post-final-dose (Day 3 of Treatment Period 2).

      Subjects will return to the unit for a final study visit 5-7 days post-last-dose for a Follow
      up Visit.

      Each subject will be involved in the study for approximately 12 weeks (including
      approximately 4 to 5 weeks for the interim analysis).

      Twelve subjects will initially be randomized to ensure at least 8 and 6 evaluable subjects at
      the end of the last treatment period for Part A and Part B respectively.
    

Intervention name(s): Treatment A; Treatment B; Treatment C; Treatment D
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Each subject will receive single dose of AZD9977 capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.; Each subject will receive single dose of AZD9977 HDL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.; Each subject will receive single dose of AZD9977 ODL capsule under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and other dose under fasted condition.; Each subject will receive single dose of AZD9977 tablet under fasting condition in Part A. If the formulation chosen for Part B, each subject will receive one dose under fed condition and another dose under fasted condition.
Other intervention name(s): AZD9977 capsule, reference; AZD9977 HDL capsule; AZD9977 ODL capsule; AZD9977 tablet
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: open-label, randomized, four-way crossover single oral dose
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Mineralocorticoid receptor; Heart failure with preserved ejection fraction; Safety; Pharmacokinetics; Influence of Food; Bioavailability