Assess the Effect of Food on Avanafil Pharmacokinetic (PK), to Compare 2 Oral Formulations of Avanafil,and Investigate Dose Proportionality in Healthy Male Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Avanafil

• Registration Number: NCT01095601
• Lead Sponsor: VIVUS LLC

Brief Summary

This study will assess the effect of food on the pharmacokinetics of avanafil (Formulation II); determine the relative bioavailability of two avanafil tablet formulations (Formulation I versus Formulation II) and will investigate the dose-proportionality of Formulation II avanafil tablet.

Detailed Description

In this Phase I, single-centre, open-label, randomized, four-period crossover study, each eligible subject will be randomized to receive the 4 treatments in a 4-way crossover fashion. The 4 treatments are as follows:

* Treatment A: 2x100 mg Formulation II avanafil tablet, fasted

* Treatment B: 2x100 mg Formulation II avanafil tablet, fed

* Treatment C: 2x100 mg Formulation I avanafil tablet, fasted

* Treatment D: 1x50 mg Formulation II avanafil tablet, fasted Subjects will report to the study site on the evening before each treatment and will remain at the site until the 24-hour PK sample has been drawn. A single oral dose of avanafil tablets will be administered with 240 mL of water. A washout period of at least 5 days will occur between the treatments. Subjects in treatment groups A, C and D will fast at least 10 hours prior to and for at least 4 hours following dosing. Subjects in treatment group B will eat a standardized high fat breakfast 30 prior to dosing. Standard meals will be provided uniformly to all subjects at approximately 4 and 9 hours after dosing, and an evening snack will be provided approximately 12 - 13 hours after dosing. Blood samples for the determination of plasma avanafil and its metabolite concentrations will be obtained from each subject at 0 (30 minutes pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 8, 12, 18 and 24 hours post-dose in each treatment period.

Adverse events; laboratory evaluations; color vision testing (Treatment A only), electrocardiogram and physical examination, vital signs will be assessed at various times during the study.

Study Timeline

• Study First Submitted: 2010-03-28
• Study First Submitted QC: 2010-03-29
• Study First Posted: 2010-03-30
• Study Start: 2010-04
• Primary Completion: 2010-05
• Study Completion: 2010-05
• Status Verified: 2011-01
• Last Update Submitted: 2011-01-05
• Last Update Posted: 2011-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

Inclusion Criteria

• adult male subjects,
• 18 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 >150 mmHg;
• diastolic blood pressure < 50 or > 95 mmHg;
• history of retinitis pigmentosa or nonarteritic anterior ischemic optic neuropathy; allergy to or previous adverse events with PDE5 inhibitors 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 prior to Day 1 in Period 1;
• use of any investigational drug within 30 days or six half-lives, whichever is longer, prior to Day 1 in Period 1;
• use of any prescription or over-the-counter drugs or herbal remedies within 14 days prior to Day 1 in Period 1;
• history of alcohol or drug abuse within 18 months, history of smoking within 6 months;
• positive urine alcohol test;
• positive cotinine test, positive urine drug screen;
• positive serology for HIV, HCV antibody, HBsAg.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment A	Avanafil	2x100 mg Formulation II avanafil tablet, fasted
Treatment B	Avanafil	2x100 mg Formulation II avanafil tablet, fed
Treatment D	Avanafil	1x50 mg Formulation II avanafil tablet, fasted
Treatment C	Avanafil	2x100 mg Formulation I avanafil tablet, fasted

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of avanafil	April through May 2010	Cmax and AUC of avanafil in each period

Secondary Outcome Measures

Name	Time	Method
Safety/AEs of avanafil	April through May, 2010	Adverse events; laboratory evaluations; color vision testing (Treatment A only), electrocardiogram and physical examination, vital signs will be assessed at various times during the study.