Study the Effect of Avanafil on the Pharmacodynamics and Pharmacokinetics of Warfarin in Healthy Male Subjects
Condition: Erectile Dysfunction
MeSH terms: Erectile Dysfunction
Study type: Interventional
Phase: Phase 1

Summary: 
      This study is designed to look into the effect of avanafil on blood levels of warfarin and to
      investigate its effect on prothrombin time/international normalized ratio (INR) in healthy
      men.
    

Detailed description: 
      The trial is a single-centre, double-blind, randomized, placebo-controlled, 2-way crossover
      drug interaction study with at least a 21-day washout period.

      Each subject will participate in two sessions in which they will be randomized to receive
      either 200 mg of avanafil or matching placebo for 9 days. On Day 3 of each period, subjects
      will receive a single dose of warfarin (25 mg). Following the warfarin dose, pharmacokinetic
      and pharmacodynamic sampling will be taken over a period of 7 days. Subjects will be
      discharged on Day 10 following the end-of-period evaluation. There will be a washout of at
      least 21 days between the warfarin doses. The study medications will be administered with 240
      mL of water following an overnight fast of at least 10 hours.

      Blood samples (3 mL) for the assessment of R- and S-warfarin concentrations in plasma will be
      drawn on Day 3 prior to warfarin administration and 0.5, 1, 1.5, 2, 4, 6, 9, 12, 24, 48, 72,
      96, 120, 144, and 168 hours after the warfarin administration.

      Blood samples (3 mL) for the assessment of avanafil and/or metabolite concentrations will be
      drawn on Day 3 prior to avanafil (or placebo) administration and at 0.5, 1, and 2 hours
      post-dose.

      Blood samples (4.5 mL) for the assessment of prothrombin time (PT) and international
      normalized ratio (INR) will be drawn at screening, check-in, on Day 3 prior to warfarin
      administration and at 6, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose.

      Blood samples (4.5 mL) for collagen-induced platelet aggregation will be drawn on Day 3 prior
      to warfarin administration and at 1, 4, 6, 12, and 24 hours post-dose.

      A blood sample (8.5 mL) for VKORC1 and CYP2C9 genotyping will be drawn at the check-in for
      Period 1.

      The overall blood volume required for this study (assuming direct venipuncture for each
      sample) will be approximately 446 mL.

      All subjects will be confined at the Clinical Research Unit starting in on Day -2 for diet
      equilibration and will remain confined for approximately 24 hours following the last study
      drug administration on Day 9.

      Adverse events, laboratory evaluations, electrocardiogram, physical examination, and vital
      signs will be assessed at various times during the study.
    

Intervention name(s): 200 mg Avanafil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 2 X 100mg tablets avanafil; 2 tablets
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: ED