Study the Effect of Avanafil on the Pharmacodynamics and Pharmacokinetics of Warfarin in Healthy Male Subjects
Primary Purpose
Erectile Dysfunction
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
200 mg Avanafil
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Erectile Dysfunction focused on measuring ED
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Avanafil
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Pharmacokinetics - PK parameters AUC, C-max and t-max of R-and S-warfarin
Pharmacodynamics - Prothrombin time, INR values, and area under effect-time curve (AUEC) of prothrombin and INR on days 14 and 15
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01095588
Brief Title
Study the Effect of Avanafil on the Pharmacodynamics and Pharmacokinetics of Warfarin in Healthy Male Subjects
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 Type
Interventional
2. Study Status
Record Verification Date
January 2011
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
VIVUS LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Erectile Dysfunction
Keywords
ED
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Avanafil
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
200 mg Avanafil
Intervention Description
2 X 100mg tablets avanafil
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
2 tablets
Primary Outcome Measure Information:
Title
Pharmacokinetics - PK parameters AUC, C-max and t-max of R-and S-warfarin
Time Frame
24 hrs
Title
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shiyin Yee, PhD
Organizational Affiliation
VIVUS LLC
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Study the Effect of Avanafil on the Pharmacodynamics and Pharmacokinetics of Warfarin in Healthy Male Subjects
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