Hemodynamic Study of Avanafil and Two α-Adrenergic Blockers,Doxazosin and Tamsulosin

This study has been completed.
Sponsor:
Information provided by:
VIVUS, Inc.
ClinicalTrials.gov Identifier:
NCT01100021
First received: January 20, 2010
Last updated: January 5, 2011
Last verified: January 2011
  Purpose

The purpose of this study is to see if avanafil causes any changes in blood pressure and pulse rate when taken with doxazosin or tamsulosin.


Condition Intervention Phase
Erectile Dysfunction
Drug: Tamsulosin and avanafil
Drug: Doxazosin and avanafil
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 1, Single-centre, Double-blind, Randomized, Placebo-controlled, Two-cohort, Two-period Crossover Study of the Hemodynamic Interactions Between Avanafil and Two α-Adrenergic Blockers, Doxazosin and Tamsulosin, in Middle-aged Healthy Male Subjects

Resource links provided by NLM:


Further study details as provided by VIVUS, Inc.:

Primary Outcome Measures:
  • The maximum decrease in blood pressure after dosing [ Time Frame: 30, 20, 10 min predose; 15, 30, 45, 60, 75, 90, 105, 120 min, 2.5, 3, 3.5, 4, 5, 6, 7, 10, 12, 18, and 24 hrs postdose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The maximum decrease in blood pressure and pulse rate after dosing [ Time Frame: 30, 20, 10 min predose; 15, 30, 45, 60, 75, 90, 105, 120 min, 2.5, 3, 3.5, 4, 5, 6, 7, 10, 12, 18, and 24 hrs postdose ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: February 2010
Study Completion Date: April 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tamsulosin + avanafil Drug: Tamsulosin and avanafil
tamsulosin - 0.4mg daily for 18 days; avanafil - 200 mg 1 x 2 days
Experimental: Doxazosin + avanafil Drug: Doxazosin and avanafil
doxazosin - 1 mg 1 x 1 day; 2 mg 1 x 2 days; 4 mg 1 x 4 days; 8 mg 1 x 11 days; avanafil - 200 mg 1 x 1 day

  Eligibility

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

Inclusion Criteria:

  1. Written Informed Consent.
  2. Adult male subjects 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 exam, etc.), in the opinion of the Investigator in consultation with the Sponsor.
  6. Male subjects should be willing to use a condom and spermicide during sexual activity for 90 days after last dosing of avanafil and be willing to not donate sperm for 90 days after dosing.

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. Inclusion of a subject with out of normal range laboratory values must be approved by VIVUS prior to subject enrollment.
  3. A predisposition to priapism, such as subjects with sickle cell disease or blood dyscrasias.
  4. Known history of cardiovascular or cerebrovascular event, any history of angina.
  5. Subjects with episode(s) 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 55 bpm at screening or 50 bpm prior to dosing.
  9. Acute illness, especially any infection, within 2 weeks of dosing.
  10. Systolic blood pressure < 90 or >150 mmHg; diastolic blood pressure < 50 or > 95 mmHg at screening or at check-in on Day -1 (2 rechecks are allowed).
  11. Subjects with benign prostatic hyperplasia or orthostatic hypotension (as evidenced by reduction of 20 mmHg or more in systolic blood pressure, reduction of 10 mmHg or more in diastolic blood pressure, or evidence of cerebral hypoperfusion upon standing from a seated position).
  12. History of retinitis pigmentosa or nonarteritic anterior ischemic optic neuropathy.
  13. Any history of bipolar disorder or psychosis, history of psychiatric hospitalization, greater than one lifetime episode of major depression.
  14. Hemoglobin < 12.0 g/dL.
  15. Subjects with liver function tests > 1.5 ULN
  16. Positive urine drug test and/or positive urine alcohol test at screening or at check-in on Day -1.
  17. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) at screening.
  18. Any history or presence of alcoholism or drug or substance abuse within 18 months or as defined by the Investigator.
  19. Allergy to or previously significant adverse events with PDE5 inhibitors, doxazosin and tamsulosin or their constituents.
  20. Use of any prescription or over-the-counter (OTC) medication, including herbal products, within the 14 days prior to Day 1. Up to 2 g per day of acetaminophen is allowed at the discretion of the Investigator.
  21. Use of any drug in Appendix 1 (drugs known to have clinical significance in inhibiting or inducing liver enzymes involved in drug metabolism [CYP P450]) within 30 days prior to Day 1.
  22. Blood donation or significant blood loss within 56 days prior to Day 1.
  23. Plasma donation within 14 days prior to Day 1.
  24. Any use of tobacco or nicotine products within 6 months prior to Day 1. Serum cotinine levels <10 ng/mL are considered to be consistent with no active smoking.
  25. Any subject who received an investigational drug within 30 days or six half-lives, whichever is longer, prior to Day 1.
  26. Evidence of any clinically significant medical, psychiatric, social or other condition by history, physical examination or laboratory studies that, in the opinion of the Investigator, would contraindicate the administration of study medications, affect compliance, interfere with study evaluations, limit study participation, or confound the interpretation of study results.
  27. Involvement in the planning and conduct of the study (applies to both VIVUS or designee staff, or staff at the investigational site).
  28. Previously participated in a trial with avanafil.
  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: NCT01100021

Locations
United States, Arizona
MDS Pharma Services Inc.,
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
VIVUS, Inc.
Investigators
Principal Investigator: Scott Sharples, MD MDS Pharma Services, Inc
  More Information

No publications provided

Responsible Party: Wes Day, PhD/VP of Clinical, Vivus, Inc
ClinicalTrials.gov Identifier: NCT01100021     History of Changes
Other Study ID Numbers: TA-017
Study First Received: January 20, 2010
Last Updated: January 5, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Erectile Dysfunction
Sexual Dysfunction, Physiological
Genital Diseases, Male
Sexual Dysfunctions, Psychological
Sexual and Gender Disorders
Mental Disorders
Tamsulosin
Doxazosin
Adrenergic Antagonists
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses
Antihypertensive Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on October 01, 2014