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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study of the Safety and Efficacy of Avanafil in the Treatment of Erectile Dysfunction Following Bilateral Nerve-Sparing Radical Prostatectomy

Phase 3
18 Years
70 Years
Not Enrolling
Prostate Cancer, Erectile Dysfunction

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Trial Information

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study of the Safety and Efficacy of Avanafil in the Treatment of Erectile Dysfunction Following Bilateral Nerve-Sparing Radical Prostatectomy

Avanafil is a rapidly-acting, highly specific PDE5 inhibitor under investigation for the
treatment of erectile dysfunction (ED).

The dose selection and timing of medication ingestion in relation to attempted sexual
activity in this study is based on data from pre-clinical pharmacology studies and results
of Phase 1 and 2 clinical trials examining the pharmacokinetics, pharmacodynamics, safety,
and tolerability of avanafil at doses of 50, 100, 200, and 300 mg. On the basis of these
results, 100 and 200 mg doses of avanafil are expected to define the range of doses that are
effective and well-tolerated for treatment of ED in this population. This study will
evaluate the safety and efficacy of these two dose levels of avanafil in the treatment of ED
in a population of men with ED following bilateral nerve-sparing radical prostatectomy.

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled,
parallel-design, three-arm trial to assess the safety and efficacy of avanafil in the
treatment of mild-to-severe ED in men following bilateral nerve-sparing radical

Subjects will complete a 4-week non-treatment run-in period during which they will maintain
a diary of all attempts at sexual intercourse. At the conclusion of the run-in period,
subjects with a 50% or greater failure rate in maintaining an erection for a sufficient
duration to allow successful intercourse, a score of 5-25 (inclusive) on the erectile
function (EF) domain of the IIEF questionnaire, and who made at least 4 attempts at sexual
intercourse during the run-in period will be eligible for randomization to one of the three
treatment arms: placebo, avanafil 100 mg, or avanafil 200 mg. Randomized subjects will
then complete a 12 week treatment period during which they will return to the site at 4 week
intervals for evaluation and to obtain additional study medication.

All subjects will be instructed to administer study drug about 30 minutes prior to
initiation of sexual activity and to complete a diary entry containing treatment information
and results after each use of the drug. Subjects may take up to 2 doses of study drug
within a 24-hour period provided that the doses are separated by at least 12 hours.

Inclusion Criteria:

1. Be adult males ≥ 18 years and ≤ 70 years of age at the time of screening;

2. Have a history of erectile dysfunction of at least 6 months duration following
bilateral nerve-sparing retropubic radical prostatectomy, as evidenced by an
inability to penetrate their partner on at least 50% of attempts at sexual
intercourse without the use of medical therapy;

3. Have undergone a bilateral nerve-sparing retropubic radical prostatectomy for
localized carcinoma of the prostate 6 24 months (inclusive) prior to screening;

4. Staging of prostate carcinoma ≤ pT2 and Gleason score ≤ 7 (4 ± 3);

5. Have a history of sexual potency without requiring medical therapy prior to radical

6. Be in a monogamous, heterosexual relationship with their current partner for at least
3 months;

7. Provide written informed consent;

8. Agree to make at least 4 attempts at intercourse per month;

9. Agree not to use any other treatments (including prescription or OTC medication,
herbal or naturopathic products, manual techniques, vacuum pumps, constriction
devices, experimental techniques, psychological counseling, etc.) for erectile
dysfunction during participation in this study;

10. Be willing and able to comply with all study requirements (including scheduled study
visits, treatment plans, laboratory tests and other study procedures).

Exclusion Criteria:

1. Known allergy or hypersensitivity to avanafil, sildenafil (Viagra®), vardenafil
(Levitra®), tadalafil (Cialis®) or any of the components of these drug products.

2. History of dose-limiting adverse effects during therapy with a PDE5 inhibitor or
discontinued use of a PDE5 inhibitor due to lack of efficacy at the highest tolerated

3. Concomitant use of one or more of the following medications:

1. Any nitrate, trazodone, itraconazole, ketoconazole, erythromycin, or cimetidine
(within 30 days prior to screening);

2. Other prescription or OTC drugs that are known to interfere with metabolism by
the CYP 3A4 enzyme (within 30 days prior to screening);

3. If receiving hormone replacement therapy (including thyroid supplementation),
dose that has not been stable for at least 3 months;

4. If treated with an alpha-blocker, dose that has not been stable for at least 14

4. Erectile dysfunction as a consequence of advanced neurologic disease, spinal cord
injury, or diabetes;

5. History of erectile dysfunction requiring medical therapy prior to bilateral
nerve-sparing radical prostatectomy;

6. History of previous pelvic surgery or cryotherapy of the prostate;

7. Sexual partner who is under 18 years of age, pregnant, intends to become pregnant
during the course of the study, is breastfeeding, has dyspareunia or other
gynecologic conditions or other major medical conditions that would interfere with
sexual activity or would have difficulty complying with study requirements;

8. Uncontrolled hypertension as evidenced by systolic blood pressure >170 mmHg or
diastolic blood pressure > 100 mmHg at screening;

9. Hypotension as evidenced by systolic blood pressure < 90 mmHg or diastolic blood
pressure < 50 mmHg at screening;

10. Orthostatic hypotension as evidenced by a reduction of 20 mmHg or more in systolic
blood pressure, a reduction of 10 mmHg or more in diastolic blood pressure, or
evidence of cerebral hypoperfusion (such as syncope) upon standing from a seated

11. Myocardial infarction, stroke, life-threatening arrhythmia or coronary
revascularization within the past 6 months;

12. Unstable angina, angina with sexual intercourse, or congestive heart failure > NYHA
Class II;

13. History or ECG evidence of any high-risk arrhythmia or ECG judged by the investigator
to be clinically significant;

14. Hypertrophic, obstructive, or other clinically significant cardiomyopathy, moderate
or severe cardiac valvular disease;

15. History of type 1 or type 2 diabetes, history of use of any antidiabetic medication;
HbA1c > 6.5%, and/or fasting blood glucose ≥ 126 mg/dL;

16. Clinically evident penile lesions, abrasions, anatomical deformities such as penile
fibrosis, Peyronie's disease, penile implants, urinary tract or bladder infection, or
sexually transmissible disease that the investigator deems to be clinically

17. Condition(s) predisposing to priapism, such as sickle cell disease, multiple myeloma,
or leukemia;

18. History of any malignancy other than carcinoma of the prostate (except basal cell
carcinoma or squamous cell carcinoma of the skin successfully treated by curative

19. Detectable levels of prostate specific antigen (PSA) at screening;

20. Prior use of, or likely to require radiotherapy, chemotherapy, androgen deprivation
therapy, cryotherapy, non-nerve-sparing surgery, and/or bladder or penile surgery
during the study;

21. AST or ALT > 2.0 x ULN or other evidence of significant hepatic impairment;

22. Serum creatinine > 2.5 mg/dL, estimated creatinine clearance < 60 mL/min
(Cockcroft-Gault), on dialysis, or history of renal transplantation;

23. Untreated hypogonadism or serum total testosterone < 325 ng/dL (early morning

24. Abnormal laboratory values) judged to be clinically significant by the Investigator;

25. Positive STD screen (syphilis, gonorrhea, and/or chlamydia) at screening;

26. Positive for HIV, HCV Ab, and/or HBsAg at screening;

27. History of drug, alcohol, or substance abuse within 12 months of entry;

28. Positive urine drug screen;

29. Positive breath alcohol test at screening;

30. History of retinitis pigmentosa or nonarteritic anterior ischemic optic neuropathy;

31. Use of any prescription, OTC, herbal, "male enhancement", or naturopathic treatment
or device for treatment of erectile dysfunction within two weeks prior to beginning
the 4-week, non-treatment run-in period or at any time during the study;

32. Use of any investigational medication or device for any indication within 30 days
prior to enrollment or at any time during this study;

33. Previous participation in any other investigational study of avanafil (TA-1790);

34. Any history of bipolar disorder or psychosis, greater than one lifetime episode of
major depression, current depression of moderate or greater severity or
antidepressant use that has not been stable for at least 3 months;

35. Involvement in the planning and conduct of the study on the part of subject or

36. 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,
contraindicate sexual activity or confound the interpretation of study results

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

The primary outcome variable is the subject's score on the IIEF questionnaire for questions 3, 4 and 5.

Outcome Description:

The percentage of sexual attempts in which subjects are able to maintain an erection of sufficient duration to have successful intercourse.

Outcome Time Frame:

Measured at the end of 12 week treatment period

Safety Issue:


Principal Investigator

Arthur L. Burnett, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University


United States: Food and Drug Administration

Study ID:




Start Date:

October 2009

Completion Date:

January 2011

Related Keywords:

  • Prostate Cancer
  • Erectile Dysfunction
  • Prostate Cancer
  • Erectile Dysfunction
  • Radical Prostatectomy
  • Prostatic Neoplasms
  • Erectile Dysfunction



Johns Hopkins HospitalBaltimore, Maryland  21287