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

NCT ID: NCT01095601

Last Updated: 2011-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2010-05-31

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Treatment A

2x100 mg Formulation II avanafil tablet, fasted

Group Type: OTHER

Avanafil

Intervention Type: DRUG

• 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

Treatment B

2x100 mg Formulation II avanafil tablet, fed

Group Type: OTHER

Avanafil

Intervention Type: DRUG

• 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

Treatment C

2x100 mg Formulation I avanafil tablet, fasted

Group Type: OTHER

Avanafil

Intervention Type: DRUG

• 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

Treatment D

1x50 mg Formulation II avanafil tablet, fasted

Group Type: OTHER

Avanafil

Intervention Type: DRUG

• 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

Interventions

Avanafil

• 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

Intervention Type: DRUG

Other Intervention Names

TA-1790

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

VIVUS LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Vivus, Inc

Principal Investigators

Shiyin Yee

Role: STUDY_DIRECTOR

VIVUS LLC

Other Identifiers

TA-020

Identifier Type: -

Identifier Source: org_study_id