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Study the Effect of Avanafil on the Pharmacodynamics and Pharmacokinetics of Warfarin 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. Identifier: NCT01095588
Recruitment Status : Completed
First Posted : March 30, 2010
Last Update Posted : January 7, 2011
Information provided by:

Brief 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.

Condition or disease Intervention/treatment Phase
Erectile Dysfunction Drug: 200 mg Avanafil Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I, Single-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Arm Study of the Effects of Avanafil on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects
Study Start Date : April 2010
Actual Primary Completion Date : May 2010
Actual Study Completion Date : May 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners
Drug Information available for: Avanafil

Arm Intervention/treatment
Experimental: Avanafil Drug: 200 mg Avanafil
2 X 100mg tablets avanafil

Placebo Comparator: Placebo Drug: Placebo
2 tablets

Primary Outcome Measures :
  1. Pharmacokinetics - PK parameters AUC, C-max and t-max of R-and S-warfarin [ Time Frame: 24 hrs ]
  2. Pharmacodynamics - Prothrombin time, INR values, and area under effect-time curve (AUEC) of prothrombin and INR on days 14 and 15 [ Time Frame: 24 hours ]

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.

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Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • adult male subjects,
  • 21 to 45 years of age,
  • must be medically healthy with no clinically significant screening results.

Exclusion Criteria:

  • history or clinical evidence of clinically relevant cardiovascular (including thromboembolic disorders), hepatic, renal, hematological, endocrine, pulmonary, gastrointestinal, psychiatric or neurological impairment;
  • any clinically significant laboratory abnormalities as judged by the investigator;
  • systolic blood pressure < 90 or >120 mmHg;
  • diastolic blood pressure < 50 or > 90 mmHg;
  • allergy to or previous adverse events with PDE5 inhibitors, warfarin or their constituents;
  • use of prescription or over-the-counter drugs that are known to interfere with metabolism by the cytochrome P450 3A4 enzyme within 30 days of screening;
  • use of any investigational drug within 30 days of screening; use of any prescription or over-the-counter drugs or herbal remedies within 14 days of screening;
  • history of alcohol or drug abuse within 18 months, history of smoking within 6 months;
  • positive urine alcohol and drug test;
  • positive serum cotinine test;
  • positive serology for HIV, HCV, HBsAg.

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 identifier (NCT number): NCT01095588

Sponsors and Collaborators
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Study Director: Shiyin Yee, PhD VIVUS, Inc.

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Responsible Party: Wesley Day, VP Clinical, Vivus, Inc. Identifier: NCT01095588    
Other Study ID Numbers: TA-016
First Posted: March 30, 2010    Key Record Dates
Last Update Posted: January 7, 2011
Last Verified: January 2011
Keywords provided by VIVUS, Inc.:
Additional relevant MeSH terms:
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Erectile Dysfunction
Sexual Dysfunction, Physiological
Genital Diseases, Male
Sexual Dysfunctions, Psychological
Mental Disorders