Research Evaluating an Investigational Medication for Erectile Dysfunction - Post-Prostatectomy

• Sponsor: VIVUS LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00895011
• Collaborator: (none)
• Enrollment: 298
• Locations: 51
• Arms: 3
• Duration (Months): 24
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objectives of this study are to evaluate the safety and efficacy of two doses of avanafil in the treatment of adult males for erectile dysfunction following bilateral nerve-sparing radical prostatectomy.

Condition or Disease	Intervention/Treatment	Phase
Erectile Dysfunction	Drug: Placebo; Drug: Avanafil; Drug: Avanafil	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 298 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; One dose 30 minutes prior to initiation of sexual activity
Experimental: Avanafil 100 mg	Drug: Avanafil; One dose 30 minutes prior to initiation of sexual activity; Other Names: TA-1790 Stendra
Experimental: Avanafil 200 mg	Drug: Avanafil; One dose 30 minutes prior to initiation of sexual activity; Other Names: TA-1790 Stendra

Outcome Measures

Primary Outcome Measures

1. Change in Percentage of Sexual Attempts in Which Subjects Are Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse [Baseline, Week 12]

   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?"

2. The Change in Percentage of Sexual Attempts in Which Subjects Are Able to Insert the Penis Into the Partner's Vagina [Baseline, Week 12]

   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?"

3. 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 scores from questions 1-5 & 15 range from 1 to 30. A higher score indicates better erectile function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult males ≥ 18 years and ≤ 70 years;

• Have a history of erectile dysfunction of at least 6 months duration following bilateral nerve-sparing retropubic radical prostatectomy;

• Have a PSA level consistent with the absence of prostate cancer;

• Have a history of sexual potency prior to radical prostatectomy without requiring medical therapy;

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

• Provide written informed consent;

• Agree to make at least 4 attempts at intercourse per month;

• Agree not to use any other treatments for erectile dysfunction;

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

Exclusion Criteria

• Allergy or hypersensitivity to PDE5 inhibitors or any of the components of these drug products;

• History of dose-limiting AEs during prior treatment with a PDE5 inhibitor or discontinued use of a PDE5 inhibitor due to lack of efficacy at the highest tolerated dose;

• Concomitant use of one or more of the following medications:

• Any nitrate, trazodone, itraconazole, ketoconazole, erythromycin, or cimetidine;

• Other prescription or OTC drugs that are known to interfere with metabolism by the CYP 3A4 enzyme;

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

• If treated with an alpha blocker, dose that has not been stable for at least 14 days;

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

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

• History of previous pelvic surgery, brachytherapy, or cryotherapy of the prostate;

• 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;

• Uncontrolled hypertension;

• Hypotension;

• Orthostatic hypotension;

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

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

• History or ECG evidence of any high-risk arrhythmia or clinically significant ECG;

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

• Type 1 or type 2 diabetes, history of use of any antidiabetic medication;

• 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 significant;

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

• Any malignancy other than carcinoma of the prostate (except basal cell carcinoma or squamous cell carcinoma of the skin);

• 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;

• Evidence of significant hepatic impairment;

• On dialysis, or history of renal transplantation;

• Untreated hypogonadism or low serum total testosterone;

• Abnormal laboratory value(s) judged to be clinically significant by the investigator;

• Positive STD screen (syphilis, gonorrhea, or chlamydia);

• Positive for HIV, HCV Ab, or HBsAg at screening;

• History or current drug, alcohol, or substance abuse;

• Positive urine drug screen;

• Positive breath alcohol test;

• Retinitis pigmentosa or nonarteritic anterior ischemic optic neuropathy;

• Use of any treatment or device for treatment of erectile dysfunction;

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

• Previous participation in any other investigational study of avanafil;

• 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;

• Involvement in the planning and conduct of the study on the part of subject or partner;

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Phoenix	Arizona	United States	85050
2	Research Site	Laguna Hills	California	United States	92653
3	Research Site	Los Angeles	California	United States	90073
4	Research Site	Los Angeles	California	United States	90095
5	Research Site	Sacramento	California	United States	95817
6	Research Site	Aurora	Colorado	United States	80045
7	Research Site	Englewood	Colorado	United States	80113
8	Research Site	Parker	Colorado	United States	80134
9	Research Site	Washington	District of Columbia	United States	20006
10	Research Site	Jacksonville	Florida	United States	32224
11	Research Site	Miami	Florida	United States	33136
12	Research Site	Trinity	Florida	United States	34655
13	Research Site	Chicago	Illinois	United States	60611
14	Research Site	Chicago	Illinois	United States	60637
15	Research Site	Springfield	Illinois	United States	62703
16	Research Site	Indianapolis	Indiana	United States	46202
17	Research Site	New Orleans	Louisiana	United States	70112
18	Research Site	Shreveport	Louisiana	United States	71106
19	Research Site	Baltimore	Maryland	United States	21287
20	Research Site	Towson	Maryland	United States	21204
21	Research Site	Brighton	Massachusetts	United States	02135
22	Research Site	Burlington	Massachusetts	United States	01805
23	Research Site	Jamaica Plain	Massachusetts	United States	02130
24	Research Site	Ann Arbor	Michigan	United States	48109
25	Research Site	Hackensack	New Jersey	United States	07601
26	Research Site	Lawrenceville	New Jersey	United States	08648
27	Research Site	Brooklyn	New York	United States	11215
28	Research Site	Brooklyn	New York	United States	11235
29	Research Site	Garden City	New York	United States	11530
30	Research Site	Great Neck	New York	United States	11021
31	Research Site	New York	New York	United States	10016
32	Research Site	New York	New York	United States	10029
33	Research Site	New York	New York	United States	10065
34	Research Site	Poughkeepsie	New York	United States	12601
35	Research Site	Durham	North Carolina	United States	27710
36	Research Site	Greensboro	North Carolina	United States	27403
37	Research Site	Cincinnati	Ohio	United States	45212
38	Research Site	Cleveland	Ohio	United States	44195
39	Research Site	Bala Cynwyd	Pennsylvania	United States	19004
40	Research Site	Philadelphia	Pennsylvania	United States	19107
41	Research Site	Philadelphia	Pennsylvania	United States	19111
42	Research Site	Myrtle Beach	South Carolina	United States	29572
43	Research Site	Rock Hill	South Carolina	United States	29732
44	Research Site	Nashville	Tennessee	United States	37232
45	Research Site	Arlington	Texas	United States	76017
46	Research Site	Houston	Texas	United States	77030
47	Research Site	San Antonio	Texas	United States	78229
48	Research Site	Temple	Texas	United States	76508
49	Research Site	Charlottesville,	Virginia	United States	22908
50	Research Site	Fairfax	Virginia	United States	22030
51	Research Site	Richmond	Virginia	United States	23235

Sponsors and Collaborators

• VIVUS LLC

Investigators

• Study Director: John Mulhall, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VIVUS LLC
• ClinicalTrials.gov Identifier: NCT00895011
• Other Study ID Numbers: TA-303; NCT01171001
• First Posted: May 7, 2009
• Last Update Posted: Oct 1, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by VIVUS LLC: Erectile Dysfunction; E.D.
• Additional relevant MeSH terms: Erectile Dysfunction

Study Results

Participant Flow

Recruitment Details	Subject recruitment occurred at US investigative sites between April 2009 and December 2010.
Pre-assignment Detail	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.

Arm/Group Title	Placebo	Avanafil 100 mg	Avanafil 200 mg
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity	avanafil 100 mg 30 minutes orally prior to initiation of sexual activity	avanafil 200 mg 30 minutes orally prior to initiation of sexual activity
Period Title: Overall Study
STARTED	100	99	99
COMPLETED	76	85	91
NOT COMPLETED	24	14	8

Baseline Characteristics

Arm/Group Title	Placebo	Avanafil 100 mg	Avanafil 200 mg	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	100	99	99	298
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	85 85%	81 81.8%	84 84.8%	250 83.9%
>=65 years	15 15%	18 18.2%	15 15.2%	48 16.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.6 (5.87)	58.9 (5.88)	57.7 (6.60)	58.4 (6.13)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	100 100%	99 100%	99 100%	298 100%
Region of Enrollment (participants) [Number]
United States	100 100%	99 100%	99 100%	298 100%

Outcome Measures

1. Primary Outcome

Title	Change in Percentage of Sexual Attempts in Which Subjects Are Able to Maintain an Erection of Sufficient Duration to Have Successful Intercourse
Description	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, Week 12

Outcome Measure Data

Analysis Population Description

Number of participants analyzed represents the Intent-to-Treat population.

Arm/Group Title	Placebo	Avanafil 100 mg	Avanafil 200 mg
Arm/Group Description	placeb 30 minutes orally prior to initiation of sexual activity	avanafil 100 mg 30 minutes orally prior to initiation of sexual activity	avanafil 200 mg 30 minutes orally prior to initiation of sexual activity
Measure Participants	96	94	96
Least Squares Mean (Standard Error) [percentage of sexual attempts]	13.9 (3.42)	28.0 (3.54)	29.4 (3.33)

2. Primary Outcome

Title	The Change in Percentage of Sexual Attempts in Which Subjects Are Able to Insert the Penis Into the Partner's Vagina
Description	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, Week 12

Outcome Measure Data

Analysis Population Description

Number of participants analyzed represents the Intent-to-Treat population.

Arm/Group Title	Placebo	Avanafil 100 mg	Avanafil 200 mg
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity	avanafil 100 mg 30 minutes orally prior to initiation of sexual activity	avanafil 200 mg 30 minutes orally prior to initiation of sexual activity
Measure Participants	96	94	96
Least Squares Mean (Standard Deviation) [Percentage of Sexual Attempts]	7.5 (3.68)	22.3 (3.66)	27.7 (3.48)

3. Primary Outcome

Title	Change in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Score
Description	Questionnaire assesses subject's evaluation of erectile function over the previous 4-week period. Total scores from questions 1-5 & 15 range from 1 to 30. A higher score indicates better erectile function.
Time Frame	Baseline, End of Treatment (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

Number of participants analyzed represents the Intent-to-Treat population. For dropouts or missing data, the last observation carried forward convention was used.

Arm/Group Title	Placebo	Avanafil 100 mg	Avanafil 200 mg
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity	avanafil 100 mg 30 minutes orally prior to initiation of sexual activity	avanafil 200 mg 30 minutes orally prior to initiation of sexual activity
Measure Participants	95	94	96
Least Squares Mean (Standard Error) [scores on a scale]	1.2 (1.16)	4.7 (1.18)	6.2 (1.11)

Adverse Events

Time Frame	AE reporting began when the subject provided written informed consent and extended until 28 calendar days after the last dose of the investigational product was administered, or until the subject was discontinued from the study, whichever was later.
Adverse Event Reporting Description	A treatment-emergent adverse event (TEAE) is an adverse event occurring on or after the first dose of study medication, or on or after the first dispensed date if missing, and prior to the last visit.
Arm/Group Title	Placebo		Avanafil 100 mg		Avanafil 200 mg
Arm/Group Description
All Cause Mortality
	Placebo		Avanafil 100 mg		Avanafil 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Avanafil 100 mg		Avanafil 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		0/99 (0%)		0/99 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Avanafil 100 mg		Avanafil 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/100 (1%)		16/99 (16.2%)		27/99 (27.3%)
Infections and infestations
Nasopharyngitis	0/100 (0%)	0	3/99 (3%)	3	5/99 (5.1%)	5
Nervous system disorders
Headache	1/100 (1%)	1	8/99 (8.1%)	19	12/99 (12.1%)	35
Vascular disorders
Flushing	0/100 (0%)	0	5/99 (5.1%)	30	10/99 (10.1%)	31

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After Sponsor's written notification that publication of results is no longer planned or 12 months after termination of the study at all sites, Institution & PI may publish, upon written approval from Sponsor, results of the Study. Sponsor will be given the opportunity to review any proposed publication at least 60 days prior to submission for publication or disclosure. Upon Sponsor's written request, Institution and PI shall not publish or disclose information related to the Study.