REVIVE: Research Evaluating an Investigational Medication for Erectile Dysfunction - General ED

• Sponsor: VIVUS LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00790751
• Collaborator: (none)
• Enrollment: 646
• Locations: 41
• Arms: 4
• Duration (Months): 9
• Patients Per Site: 15.8
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This study is being conducted to compare the safety and efficacy of 3 doses of avanafil to placebo in men with mild to severe erectile dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Erectile Dysfunction	Drug: placebo; Drug: avanafil; Drug: avanafil; Drug: avanafil	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 646 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Avanafil (TA-1790) in Subjects With Generalized Erectile Dysfunction
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo	Drug: placebo; 30 minutes orally prior to initiation of sexual activity
Experimental: avanafil 50 mg	Drug: avanafil; 30 minutes orally prior to initiation of sexual activity; Other Names: TA-1790 Stendra
Experimental: avanafil 100 mg	Drug: avanafil; 30 minutes orally prior to initiation of sexual activity; Other Names: TA-1790 Stendra
Experimental: avanafil 200 mg	Drug: avanafil; 30 minutes orally 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 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?"

2. 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?"

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male subjects, age ≥ 18 years;

• Minimum 6 month history of mild to severe erectile dysfunction;

• 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);

• History of type 1 or type 2 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35209
2	Research Site	Homewood	Alabama	United States	35209
3	Research Site	Tucson	Arizona	United States	85712
4	Research Site	Sacramento	California	United States	95821
5	Research Site	San Diego	California	United States	92120
6	Research Site	San Diego	California	United States	92123
7	Research Site	Waterbury	Connecticut	United States	06708
8	Research Site	Clearwater	Florida	United States	33756
9	Research Site	Clearwater	Florida	United States	33761
10	Research Site	Coral Gables	Florida	United States	33134
11	Research Site	Hialeah	Florida	United States	33012
12	Research Site	Jacksonville	Florida	United States	32205
13	Research Site	Jacksonville	Florida	United States	32259
14	Research Site	Jupiter	Florida	United States	33458
15	Research Site	Ocala	Florida	United States	34471
16	Research Site	Pembroke Pines	Florida	United States	33024
17	Research Site	Tampa	Florida	United States	33624
18	Research Site	Atlanta	Georgia	United States	30308
19	Research Site	Atlanta	Georgia	United States	30328
20	Research Site	Wichita	Kansas	United States	67205
21	Research Site	Madisonville	Kentucky	United States	42431
22	Research Site	Shreveport	Louisiana	United States	71106
23	Research Site	Kansas City	Missouri	United States	64114
24	Research Site	Lawrenceville	New Jersey	United States	08648
25	Research Site	Albany	New York	United States	12206
26	Research Site	New York	New York	United States	10016
27	Research Site	Cary	North Carolina	United States	27518
28	Research Site	Charlotte	North Carolina	United States	28207
29	Research Site	Charlotte	North Carolina	United States	28209
30	Research Site	Harrisburg	North Carolina	United States	28075
31	Research Site	Hickory	North Carolina	United States	28601
32	Research Site	Raleigh	North Carolina	United States	27609
33	Research Site	Salisbury	North Carolina	United States	28144
34	Research Site	Wilmington	North Carolina	United States	28401
35	Research Site	Winston-Salem	North Carolina	United States	27103
36	Research Site	Beachwood	Ohio	United States	44122
37	Research Site	Bala Cynwyd	Pennsylvania	United States	19004
38	Research Site	Lancaster	Pennsylvania	United States	17601
39	Research Site	El Paso	Texas	United States	79925
40	Research Site	Houston	Texas	United States	77074
41	Research Site	Spring	Texas	United States	77386

Sponsors and Collaborators

• VIVUS LLC

Investigators

• Principal Investigator: Irwin Goldstein, MD, San Diego Sexual Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VIVUS LLC
• ClinicalTrials.gov Identifier: NCT00790751
• Other Study ID Numbers: TA-301
• First Posted: Nov 13, 2008
• Last Update Posted: Jul 11, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by VIVUS LLC: ED; Erectile Dysfunction; Dysfunction; Erectile
• Additional relevant MeSH terms: Erectile Dysfunction

Study Results

Participant Flow

Recruitment Details	Subject recruitment occurred at US investigative sites between November 2008 and April 2009.
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 50 mg	Avanafil 100 mg	Avanafil 200 mg
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity	avanafil 50 mg 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	162	161	161	162
COMPLETED	137	131	141	141
NOT COMPLETED	25	30	20	21

Baseline Characteristics

Arm/Group Title	Placebo	Avanafil 50 mg	Avanafil 100 mg	Avanafil 200 mg	Total
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity	avanafil 50 mg 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	Total of all reporting groups
Overall Participants	162	161	161	162	646
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.4 (11.13)	55.4 (10.81)	56.5 (10.32)	55.7 (11.33)	55.7 (10.89)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	162 100%	161 100%	161 100%	162 100%	646 100%
Region of Enrollment (participants) [Number]
United States	162 100%	161 100%	161 100%	162 100%	646 100%

Outcome Measures

1. Primary Outcome

Title	Change in Percentage of Sexual Attempts in Which Subjects Were 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, 12 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Avanafil 50 mg	Avanafil 100 mg	Avanafil 200 mg
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity	avanafil 50 mg 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	155	154	157	156
Least Squares Mean (Standard Error) [percentage of sexual attempts]	14.1 (2.57)	27.8 (2.58)	43.4 (2.56)	44.2 (2.57)

2. Primary Outcome

Title	Change in Percentage of Sexual Attempts in Which Subjects Were 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, 12 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Avanafil 50 mg	Avanafil 100 mg	Avanafil 200 mg
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity	avanafil 50 mg 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	155	154	157	156
Least Squares Mean (Standard Error) [percentage of sexual attempts]	7.1 (2.33)	18.2 (2.34)	27.2 (2.32)	29.8 (2.33)

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 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)

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 50 mg	Avanafil 100 mg	Avanafil 200 mg
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity	avanafil 50 mg 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	152	152	156	155
Least Squares Mean (Standard Error) [scores on a scale]	2.9 (0.57)	5.4 (0.57)	8.3 (0.56)	9.5 (0.56)

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	# participants at risk is presented for the safety population. The Safety Population was defined as all subjects who took at least one dose of study drug and had safety data available.
Arm/Group Title	Placebo		Avanafil 50 mg		Avanafil 100 mg		Avanafil 200 mg
Arm/Group Description	placebo 30 minutes orally prior to initiation of sexual activity		avanafil 50 mg 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
All Cause Mortality
	Placebo		Avanafil 50 mg		Avanafil 100 mg		Avanafil 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Avanafil 50 mg		Avanafil 100 mg		Avanafil 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/161 (1.2%)		1/160 (0.6%)		3/161 (1.9%)		3/162 (1.9%)
Cardiac disorders
Acute myocardial infarction	0/161 (0%)	0	1/160 (0.6%)	1	0/161 (0%)	0	0/162 (0%)	0
Coronary artery disease	0/161 (0%)	0	0/160 (0%)	0	0/161 (0%)	0	1/162 (0.6%)	1
General disorders
Non-cardiac chest pain	1/161 (0.6%)	1	0/160 (0%)	0	0/161 (0%)	0	0/162 (0%)	0
Infections and infestations
Infected bites	0/161 (0%)	0	0/160 (0%)	0	0/161 (0%)	0	1/162 (0.6%)	1
Injury, poisoning and procedural complications
Gun shot wound	0/161 (0%)	0	0/160 (0%)	0	1/161 (0.6%)	1	0/162 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	0/161 (0%)	0	0/160 (0%)	0	1/161 (0.6%)	1	0/162 (0%)	0
Prostate cancer stage I	0/161 (0%)	0	0/160 (0%)	0	1/161 (0.6%)	1	0/162 (0%)	0
Nervous system disorders
Hypoaesthesia	0/161 (0%)	0	0/160 (0%)	0	0/161 (0%)	0	1/162 (0.6%)	1
Psychiatric disorders
Depression suicidal	1/161 (0.6%)	1	0/160 (0%)	0	0/161 (0%)	0	0/162 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Avanafil 50 mg		Avanafil 100 mg		Avanafil 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/161 (4.3%)		16/160 (10%)		28/161 (17.4%)		31/162 (19.1%)
Infections and infestations
Nasopharyngitis	2/161 (1.2%)		1/160 (0.6%)		2/161 (1.2%)		6/162 (3.7%)
Bronchitis	1/161 (0.6%)		3/160 (1.9%)		1/161 (0.6%)		4/162 (2.5%)
Nervous system disorders
Headache	2/161 (1.2%)		7/160 (4.4%)		12/161 (7.5%)		15/162 (9.3%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	2/161 (1.2%)		1/160 (0.6%)		7/161 (4.3%)		3/162 (1.9%)
Vascular disorders
Flushing	0/161 (0%)		6/160 (3.8%)		10/161 (6.2%)		6/162 (3.7%)

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.