To Evaluate The Effect Of Ketoconazole, Ritonavir and Erythromycin on the Safety and Pharmacokinetics of Avanafil

NCT00770042 | Completed Phase 1

• 1 other identifier: TA-011
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to examine the effect of three CYP3A4 inhibitors (ketoconazole, erythromycin and ritonavir) on the single dose pharmacokinetics of avanafil. Ketoconazole and ritonavir are potent inhibitors of CYP3A4 and erythromycin is a moderate CYP3A4 inhibitor. Any interaction that is observed would be predictive of other inhibitors of CYP3A4.

Conditions

Erectile Dysfunction

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety of avanafil when administered with Ketoconazole, ritonavir, or erythromycin and to assess the effect of co-administration of these drugs on the pharmacokinetics of avanafil

  9 days

Study Arms (3)

Group 1

EXPERIMENTAL

Ketoconazole 400 mg qd for 5 days (Days 2-6) plus a single dose of 50 mg avanafil on Days 1 and 6

Drug: Ketoconazole; Drug: Avanafil

Group 2

EXPERIMENTAL

Erythromycin 500mg every 12 hours for 5 days (Days 2-6) plus a single dose of 200 mg Avanafil on Days 1 and 6.

Drug: Erythomycin; Drug: Avanafil

Group 3

EXPERIMENTAL

Ritonavir 300 mg bid for 1 day (Day 2), 400 mg bid for 1 day (Day 3), 600 mg bid for 5 days (Day 4-8) plus a single dose of 50 mg avanafil on Days 1 and 8

Drug: Ritonavir; Drug: Avanafil

Interventions

Ritonavir DRUG

Ritonavir 300 mg bid for 1 day (Day 2), 400 mg bid for 1 day (Day 3), 600 mg bid for 5 days (Day 4-8)

Group 3

Ketoconazole DRUG

Ketoconazole 400 mg qd for 5 days (Days 2-6)

Group 1

Erythomycin DRUG

Erythromycin 500 mg every 12 hours for 5 days (Days 2-6)

Group 2

Avanafil DRUG

Avanafil 50 mg on Days 1 and 8

Group 3

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males, 21 to 45 years of age (inclusive).
• A body weight of at least 50 kg and a body mass index (BMI) between 21 and 28 kg/m2, inclusive
• Medically healthy, with clinically insignificant screening results \[e.g., laboratory profiles, medical histories, ECGs, physical exam, etc., in the opinion of the investigator.
• Subjects are able to communicate with the investigator, and to understand and comply with all requirements of study participation.
• Voluntarily consent to participate in the study
• The subject must agree not to donate his sperm during and within 3-months of the completion of the study.
• All sexually active male subjects and their female partners of childbearing potential must agree to use adequate contraception methods, for the specified time.

You may not qualify if:

• A history or presence of significant cardiovascular, neurological, hematological, psychiatric, hepatic, gastrointestinal, pulmonary, endocrine, immunologic or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs or place the subjects at increased risk as determined by the investigator.
• Any clinically significant laboratory abnormalities as judged by the investigator.
• Systolic blood pressure \< 90 or \>140 mmHg; diastolic blood pressure \< 50 or \> 90 mmHg at screening or at check-in on day 1 in treatment period 1.
• Positive urine drug test and/or positive breath alcohol test.
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) at screening.
• Any history or presence of alcoholism or drug or substance abuse.
• Allergy to or previous adverse events with PDE5 inhibitors, ketoconazole, ritonavir and/or erythromycin or their constituents.
• Use of any prescription or over-the-counter (OTC) medication, including herbal products.
• Use of any drugs known to have clinical significance in inhibiting or inducing liver enzymes involved in drug metabolism
• Blood donation or significant blood loss.
• Any use of tobacco or nicotine products within 6 months.
• Any history of celiac diseases, food allergies, and those on vegetarian or other diets incompatible with study objectives.
• Any subject who received an investigational drug within 30 days .
• Clinical judgment by the investigator that the subject should not participate in the study.

Sponsors & Collaborators

• VIVUS LLC: lead

Study Sites (1)

Research Site

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Conditions

Erectile Dysfunction

Interventions

Ritonavir; Ketoconazole; eryF protein, Saccharopolyspora erythraea; avanafil

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Shiyin Yee, PhD

  VIVUS LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 6, 2008
• First Posted: October 9, 2008
• Study Start: October 1, 2008
• Primary Completion: November 1, 2008
• Study Completion: December 1, 2008
• Last Updated: December 2, 2009

Record last verified: 2009-11

Locations

US (1)