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Drug Interaction Study of Avanafil and Enalapril or Amlodipine

This study has been completed.
Sponsor:
Information provided by:
VIVUS, Inc.
ClinicalTrials.gov Identifier:
NCT01117038
First received: April 23, 2010
Last updated: August 9, 2011
Last verified: August 2011
  Purpose

The purpose of this study is to determine the change in the blood pressure and pulse rate, pharmacokinetics and the safety when avanafil is taken with either enalapril or amlodipine.


Condition Intervention Phase
Erectile Dysfunction
Drug: avanafil and enalapril
Drug: avanafil and amlodipine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I, Double-Blind, Randomized, Placebo-Controlled, Two-Period, Two-Cohort Crossover Study to Assess the Potential Interaction of Avanafil on the Pharmacokinetic and/or Hemodynamic Effects of Enalapril or Amlodipine in Male Subjects

Resource links provided by NLM:


Further study details as provided by VIVUS, Inc.:

Primary Outcome Measures:
  • To measure the change in standing blood pressure after dosing [ Time Frame: -0.5, -0.25, -0.17, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 22 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To measure the pharmacokinetic parameters of taking avanafil with enalapril [ Time Frame: before dosing and after dosing at the hours of 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36, 48 ] [ Designated as safety issue: Yes ]
    AUCc-tau Cmax Cmin Tmax AUC0-t AUC0-inf t1/2 Kel

  • To measure the change in sitting and lying blood pressure and pulse rate after dosing [ Time Frame: -0.5, -0.33, -0.17, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 22 hours ] [ Designated as safety issue: Yes ]
  • To determine the effects of enalapril on blood pressure and pulse rate [ Time Frame: -0.5, -0.33, -0.17, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 22 hours ] [ Designated as safety issue: Yes ]
  • To measure the pharmacokinetic parameters of taking avanafil with amlodipine [ Time Frame: before dosing and after dosing at the hours of 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 36, 48 ] [ Designated as safety issue: Yes ]
    AUCc-tau Cmax Cmin Tmax AUC0-t AUC0-inf t1/2 Kel

  • To determine the effects of amlodipine on blood pressure and pulse rate [ Time Frame: -0.5, -0.33, -0.17, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 22 hours ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: April 2010
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: enalapril and avanafil Drug: avanafil and enalapril
enalapril twice a day for 11 days avanafil/placebo once a day for 2 days
Experimental: amlodipine and avanafil Drug: avanafil and amlodipine
amlodipine 5mg once a day for 16 days avanafil/placebo once a day for 3 days

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Voluntarily consent to participate in the study (informed consent form [ICF] must be signed and dated prior to any study related assessments).
  2. Adult male subjects of 40 to 65 years of age, inclusive.
  3. A body weight of at least 50 kg and a body mass index (BMI) between 18 and 32 kg/m2, inclusive [BMI will be calculated as weight in kg/(height in m)2].
  4. Subjects are able to communicate with the Investigator, and to understand and comply with all requirements of study participation.
  5. Medically healthy, with no clinically significant screening results (e.g., laboratory profiles, medical histories, ECGs, physical examinations, etc.), in the opinion of the Investigator.

Exclusion Criteria:

  1. A history or presence of significant cardiovascular (including thromboembolic disorders), 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.
  2. Any clinically significant laboratory abnormalities as judged by the Investigator.
  3. A predisposition to priapism, such as subjects with sickle cell disease or blood dyscrasias.
  4. Known history of cardiovascular or cerebrovascular event, or any history of angina.
  5. History of fainting or vasovagal hypotension.
  6. History or ECG evidence of any high-risk arrhythmia or ECG judged by the Investigator to be clinically significant.
  7. Hypertrophic obstructive or other clinically significant cardiomyopathy, moderate or severe cardiac valvular disease.
  8. Subjects whose pulse is lower than 50 bpm at screening.
  9. Acute illness, especially any infection, within 2 weeks of dosing.
  10. Supine systolic blood pressure </= 100 or >/= 140 mmHg; supine diastolic blood pressure </= 50 or >/= 95 mmHg at screening (2 rechecks are allowed).
  11. Subjects with orthostatic hypotension (as evidenced by a reduction of 30 mmHg or more in systolic blood pressure, reduction of 20 mmHg or more in diastolic blood pressure, or evidence of cerebral hypoperfusion upon standing from a seated position).
  12. Any history of bipolar disorder or psychosis, history of psychiatric hospitalization, greater than one lifetime episode of major depression.
  13. Hemoglobin < 12.0 g/dL.
  14. Positive urine drug test, positive urine alcohol test, or positive urine cotinine test at screening or at check-in on Day -1.
  15. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) at screening.
  16. Any history or presence of alcoholism or drug or substance abuse within 18 months or as defined by the Investigator.
  17. Allergy to or previous adverse events with PDE5 inhibitors, ACE inhibitors, calcium channel blockers, or their constituents.
  18. Use of any prescription or over-the-counter (OTC) medication, including herbal products, within the 14 days prior to Day 1 and throughout the study. Up to 2 g per day of acetaminophen is allowed at the discretion of the Investigator.
  19. Use of any drug in Appendix 1 (drugs known to interfere with metabolism by the CYP450 3A4 enzyme) within 30 days prior to Day 1.
  20. Blood donation or significant blood loss within 56 days prior to Day 1.
  21. Plasma donation within 14 days prior to Day 1.
  22. Any use of tobacco or nicotine products within 6 months prior to Day 1.
  23. Any subject who received an investigational drug within 30 days or six half-lives, whichever is longer, prior to Day 1.
  24. Involvement in the planning and conduct of the study (applies to both VIVUS or designee staff, or staff at the investigational site).
  25. Previously participated in a trial with avanafil.
  26. Subjects who report having difficulty swallowing tablets, capsules, etc.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01117038

Locations
United States, Arizona
Celerion
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
VIVUS, Inc.
Investigators
Study Director: Shiyin Yee, PhD VIVUS, Inc.
  More Information

No publications provided

Responsible Party: Wesley Day, Vivus, Inc.
ClinicalTrials.gov Identifier: NCT01117038     History of Changes
Other Study ID Numbers: TA-019
Study First Received: April 23, 2010
Last Updated: August 9, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by VIVUS, Inc.:
ED
Erectile Dysfunction

Additional relevant MeSH terms:
Erectile Dysfunction
Genital Diseases, Male
Mental Disorders
Sexual Dysfunction, Physiological
Sexual Dysfunctions, Psychological
Sexual and Gender Disorders
Amlodipine
Enalapril
Enalaprilat
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Enzyme Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 25, 2014