Erectile Dysfunction
Conditions
Keywords
ED, Erectile Dysfunction, Dysfunction, Diabetic, Erectile
Brief summary
This study is being conducted to compare the safety and efficacy of 2 doses of avanafil to placebo in diabetic men with mild to severe erectile dysfunction.
Interventions
DRUGplacebo
30 minutes orally prior to initiation of sexual activity
DRUGavanafil
30 minutes orally prior to initiation of sexual activity
Sponsors
VIVUS LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male subjects, age ≥ 18 years; * Minimum 6 month history of mild to severe erectile dysfunction; * Have documented diabetes (type 1 or type 2); * Subject is in a monogamous, heterosexual relationship for at least 3 months; * Subject agrees to make at least 4 attempts at intercourse per month; * Subject is willing and able to provide informed consent.
Exclusion criteria
* Allergy or hypersensitivity to PDE5 inhibitors; * History of dose-limiting AEs during therapy with a PDE5 inhibitor or hx of consistent treatment failure with other PDE5 inhibitors for therapy of ED; * Current or expected use of organic nitrates at any time during the study; * Previous or current antiandrogen therapy; * Use of prescription or over-the-counter drugs known to inhibit the activity of CYP3A4 at any time during the study; * Androgen replacement therapy that has not been stable for at least 3 month; * Initiation or change in dose of any alpha-blocker within 14 days prior to randomization; * ED as a result of spinal cord injury or radical prostatectomy; * Untreated hypogonadism or low serum total testosterone * History of or predisposition to priapism; * Any penile implant; * Elevated PSA, other evidence of prostate cancer, or previous radical prostatectomy; * History of any malignancy (except basal cell carcinoma or squamous cell carcinoma of the skin successfully treated by curative excision); * Uncontrolled diabetes; * Uncontrolled hypertension; * Hypotension; * Orthostatic hypotension; * Significant cardiovascular disease; * Abnormal ECG; * Hepatic or renal impairment; * Positive STD screen; * Clinically evident penile lesions, abrasions, or anatomical deformities; * Urinary tract or bladder infection; * Use of any treatment for erectile dysfunction other than study drug at any time during the study; * Participation in another investigational study within 30 days of screening or at any time during this study; * Previous participation in any other investigational study of avanafil; * History or current drug, alcohol, or substance abuse; * 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; * Partners who are \< 18 years of age, who are nursing, who are known to be pregnant at screening, who wish to become pregnant during the study period, who have any gynecologic problems or major medical conditions that would limit participation in sexual intercourse; * Evidence of any other condition by history, physical examination, or laboratory studies that, in the opinion of the investigator, would contraindicate the administration of study medication, affect compliance, interfere with study evaluations, limit study participation, contraindicate sexual activity, or confound the interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percentage of Sexual Attempts in Which Subjects Were Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse | Baseline, 12-weeks | Data presented as mean change from baseline in the percentage of Yes responses to Sexual Encounter Profile (SEP) diary question 3 Did your erection last long enough for you to have successful intercourse? |
| Change in Percentage of Sexual Attempts in Which Subjects Were Able to Insert the Penis Into the Partner's Vagina | Baseline, 12 Weeks | Data presented as mean change from baseline in the percentage of Yes responses to Sexual Encounter Profile (SEP) diary question 2 Were you able to insert your penis into your partner's vagina? |
| Change in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Score | Baseline, End of Treatment (up to 12 weeks) | Questionnaire assesses subject's evaluation of erectile function over the previous 4-week period. Total score from questions 1-5 & 15 ranges from 1 to 30. A higher score indicates better erectile function. |
Countries
United States
Participant flow
Recruitment details
Subject recruitment occurred at US investigative sites between December 2008 and February 2010.
Pre-assignment details
Subjects meeting the initial eligibility criteria completed a 4-week non-treatment run-in period during which information on each attempt at intercourse was recorded. At the end of the run-in, subjects meeting the randomization criteria were eligible for assignment to one of the treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo 30 minutes orally prior to initiation of sexual activity | 130 |
| Avanafil 100 mg avanafil 100 mg 30 minutes orally prior to initiation of sexual activity | 129 |
| Avanafil 200 mg avanafil 200 mg 30 minutes orally prior to initiation of sexual activity | 131 |
| Total | 390 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 |
| Overall Study | Lost to Follow-up | 4 | 2 | 9 |
| Overall Study | Protocol non-compliance | 15 | 15 | 6 |
| Overall Study | Requirement for restricted medication | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Avanafil 100 mg | Avanafil 200 mg | Total |
|---|---|---|---|---|
| Age Continuous | 58.2 years STANDARD_DEVIATION 8.62 | 58.2 years STANDARD_DEVIATION 9.62 | 57.5 years STANDARD_DEVIATION 8.99 | 58.0 years STANDARD_DEVIATION 9.07 |
| Region of Enrollment United States | 130 participants | 129 participants | 131 participants | 390 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 130 Participants | 129 Participants | 131 Participants | 390 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 130 | 18 / 127 | 27 / 131 |
| serious Total, serious adverse events | 1 / 130 | 3 / 127 | 4 / 131 |
Outcome results
Primary
Change in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Score
Questionnaire assesses subject's evaluation of erectile function over the previous 4-week period. Total score from questions 1-5 & 15 ranges from 1 to 30. A higher score indicates better erectile function.
Time frame: Baseline, End of Treatment (up to 12 weeks)
Population: Number of participants analyzed represents the Intent-to-Treat population. For dropouts or missing data, the last observation carried forward convention was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Score | 1.8 scores on a scale | Standard Deviation 0.64 |
| Avanafil 100 mg | Change in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Score | 4.5 scores on a scale | Standard Deviation 0.64 |
| Avanafil 200 mg | Change in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Score | 5.4 scores on a scale | Standard Deviation 0.66 |
Primary
Change in Percentage of Sexual Attempts in Which Subjects Were Able to Insert the Penis Into the Partner's Vagina
Data presented as mean change from baseline in the percentage of Yes responses to Sexual Encounter Profile (SEP) diary question 2 Were you able to insert your penis into your partner's vagina?
Time frame: Baseline, 12 Weeks
Population: Number of participants analyzed represents the Intent-to-Treat population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Percentage of Sexual Attempts in Which Subjects Were Able to Insert the Penis Into the Partner's Vagina | 7.5 percentage of sexual attempts | Standard Error 2.85 |
| Avanafil 100 mg | Change in Percentage of Sexual Attempts in Which Subjects Were Able to Insert the Penis Into the Partner's Vagina | 21.5 percentage of sexual attempts | Standard Error 2.85 |
| Avanafil 200 mg | Change in Percentage of Sexual Attempts in Which Subjects Were Able to Insert the Penis Into the Partner's Vagina | 25.9 percentage of sexual attempts | Standard Error 2.9 |
Primary
Change in Percentage of Sexual Attempts in Which Subjects Were Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse
Data presented as mean change from baseline in the percentage of Yes responses to Sexual Encounter Profile (SEP) diary question 3 Did your erection last long enough for you to have successful intercourse?
Time frame: Baseline, 12-weeks
Population: Number of participants analyzed represents the Intent-to-Treat population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Percentage of Sexual Attempts in Which Subjects Were Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse | 13.6 percentage of sexual attempts | Standard Error 2.77 |
| Avanafil 100 mg | Change in Percentage of Sexual Attempts in Which Subjects Were Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse | 28.7 percentage of sexual attempts | Standard Error 2.78 |
| Avanafil 200 mg | Change in Percentage of Sexual Attempts in Which Subjects Were Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse | 34.0 percentage of sexual attempts | Standard Error 2.76 |