Study Evaluating the Effects of Avanafil on Semen Parameters

• Sponsor: VIVUS LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01768676
• Collaborator: (none)
• Enrollment: 181
• Locations: 15
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 12.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether avanafil will affect different aspects of sperm production.

Condition or Disease	Intervention/Treatment	Phase
Erectile Dysfunction	Drug: avanafil; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 181 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Clinical Trial of the Effect of Avanafil (STENDRA™) on Spermatogenesis in Healthy Adult Males and Adult Males With Mild Erectile Dysfunction
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: avanafil 100 mg	Drug: avanafil; 100 mg; Other Names: TA-1790 Stendra
Placebo Comparator: Placebo placebo	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With a Greater Than or Equal to 50% Decrease in Sperm Concentration From Baseline to Week 26 [Baseline to Week 26]

   Subjects provided 2 semen samples at each visit 2 to 12 days apart. The average value is used as the visit result.

Secondary Outcome Measures

1. Percentage of Subjects With Greater Than or Equal to 50% Reduction in Sperm Count From Baseline to Week 26 [baseline to week 26]

2. Percentage of Subjects With Greater Than or Equal to 50% Reduction in Sperm Motility From Baseline to Week 26 [baseline to week 26]

   Sperm motility was based upon the WHO grading scale: grade A, B, or C.

3. Percentage of Subjects With Greater Than or Equal to 50% Reduction in Semen Volume From Baseline to Week 26 [baseline to week 26]

4. Percentage of Subjects With Greater Than or Equal to 50% Reduction in Normal Sperm Morphology From Baseline to Week 26 [baseline to week 26]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Provide written informed consent

• Able to produce semen samples without requiring therapy (PDE5 inhibitors, over-the-counter (OTC) medication, and/or herbal supplements) for erectile dysfunction

• Be medically healthy (no clinically significant screening results for medical history, electrocardiogram (ECG), laboratory studies, physical examination, etc.) in the opinion of the investigator

• Be willing and able to comply with all study requirements

Exclusion Criteria:

• An International Index of Erectile Function (IIEF) erectile function domain score of less than 17;

• History of infertility, vasectomy, testicular mass, testicular trauma, testicular abnormality (including size), radiation to the testis, previous pelvic surgery, cryotherapy of the prostate, known sperm defect, or retrograde ejaculation, or cryptorchidism;

• Resting heart rate <45 or >90 beats per minute at screening (3 rechecks permitted);

• Screening systolic blood pressure <90 or >140 mmHg and/or diastolic blood pressure <50 or >90 mmHg (3 rechecks permitted);

• High serum FSH (>18.0 mIU/mL), high serum LH (>18 mIU/mL), or low serum testosterone (< 270 ng/dL, early morning collection) on screening;

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

• Prostate specific antigen (PSA) level ≥4 ng/mL at screening;

• Individuals who perform rotating shift work during the course of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Facility	Huntsville	Alabama	United States
2	Research Facility	LA	California	United States
3	Research Facility	San Diego	California	United States
4	Research Facility	Parker	Colorado	United States
5	Research Facility	Aventura	Florida	United States
6	Research Facility	Carmel	Indiana	United States
7	Research Facility	New Orleans	Louisiana	United States
8	Research Facility	Shreveport	Louisiana	United States
9	Research Facility	Kansas City	Missouri	United States
10	Research Facility	Albany	New York	United States
11	Research Facility	New York	New York	United States
12	Research Facility	Cincinnati	Ohio	United States
13	Research Facility	Bala Cynwyd	Pennsylvania	United States
14	Research Facility	Knoxville	Tennessee	United States
15	Research Facility	San Antonio	Texas	United States

Sponsors and Collaborators

• VIVUS LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VIVUS LLC
• ClinicalTrials.gov Identifier: NCT01768676
• Other Study ID Numbers: TA-401
• First Posted: Jan 15, 2013
• Last Update Posted: Dec 14, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by VIVUS LLC: healthy male
• Additional relevant MeSH terms: Erectile Dysfunction

Study Results

Participant Flow

Arm/Group Title	Avanafil	Placebo
Arm/Group Description	100 mg once daily in the evening	placebo taken once daily in the evening
Period Title: Overall Study
STARTED	90	91
COMPLETED	66	60
NOT COMPLETED	24	31

Baseline Characteristics

Arm/Group Title	Avanafil	Placebo	Total
Arm/Group Description	100 mg once daily in the evening	placebo taken once daily in the evening	Total of all reporting groups
Overall Participants	90	91	181
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.8 (7.23)	32.9 (7.11)	33.8 (7.21)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	90 100%	91 100%	181 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 26.7%	29 31.9%	53 29.3%
Not Hispanic or Latino	66 73.3%	62 68.1%	128 70.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 3.3%	3 3.3%	6 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	28 31.1%	16 17.6%	44 24.3%
White	59 65.6%	71 78%	130 71.8%
More than one race	0 0%	1 1.1%	1 0.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	90 100%	91 100%	181 100%
Baseline sperm concentration (million sperm/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [million sperm/mL]	76.1 (43.05)	76.3 (40.65)	76.2 (41.75)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With a Greater Than or Equal to 50% Decrease in Sperm Concentration From Baseline to Week 26
Description	Subjects provided 2 semen samples at each visit 2 to 12 days apart. The average value is used as the visit result.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Completer population is defined as those who completed the study through week 26 and had semen analysis at both baseline and week 26. This may differ from the definition of completers for the study flow.

Arm/Group Title	Avanafil	Placebo
Arm/Group Description	100 mg once daily in the evening	placebo taken once daily in the evening
Measure Participants	68	69
Number [percentage of participants]	1.5 1.7%	14.5 15.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avanafil, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The difference in percentage of subjects with a >/= 50% reduction from baseline to Week 26 in sperm concentration between treatment arms was analyzed using Cochran-Mantel-Haenszel method to account for the randomization stratification by baseline sperm concentration. If upper limit of 95% CI < 20% then avanafil is considered non-inferior to placebo.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-12.93
	Confidence Interval	(2-Sided) 95%; -21.56 to -4.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.41
	Estimation Comments	Confidence interval was only calculated for primary endpoint of the difference between avanafil and placebo, not for each individual arm.

2. Secondary Outcome

Title	Percentage of Subjects With Greater Than or Equal to 50% Reduction in Sperm Count From Baseline to Week 26
Time Frame	baseline to week 26

Outcome Measure Data

Analysis Population Description

completers population

Arm/Group Title	Avanafil	Placebo
Arm/Group Description	100 mg once daily in the evening	placebo taken once daily in the evening
Measure Participants	68	69
Number [percentage of participants]	10.3 11.4%	21.7 23.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avanafil, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If upper limit of 95% CI < 20% then avanafil is considered non-inferior to placebo.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-11.4
	Confidence Interval	(2-Sided) 95%; -23.5 to 0.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.2
	Estimation Comments	Confidence interval was only calculated for primary endpoint of the difference between avanafil and placebo, not for each individual arm.

3. Secondary Outcome

Title	Percentage of Subjects With Greater Than or Equal to 50% Reduction in Sperm Motility From Baseline to Week 26
Description	Sperm motility was based upon the WHO grading scale: grade A, B, or C.
Time Frame	baseline to week 26

Outcome Measure Data

Analysis Population Description

completers population

Arm/Group Title	Avanafil	Placebo
Arm/Group Description	100 mg once daily in the evening	placebo taken once daily in the evening
Measure Participants	68	69
Number [percentage of participants]	0 0%	1.4 1.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avanafil, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If upper limit of 95% CI < 20% then avanafil is considered non-inferior to placebo.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -4.2 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments	Confidence interval was only calculated for primary endpoint of the difference between avanafil and placebo, not for each individual arm.

4. Secondary Outcome

Title	Percentage of Subjects With Greater Than or Equal to 50% Reduction in Semen Volume From Baseline to Week 26
Time Frame	baseline to week 26

Outcome Measure Data

Analysis Population Description

completers population

Arm/Group Title	Avanafil	Placebo
Arm/Group Description	100 mg once daily in the evening	placebo taken once daily in the evening
Measure Participants	68	69
Number [percentage of participants]	0 0%	2.9 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avanafil, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If upper limit of 95% CI < 20% then avanafil is considered non-inferior to placebo.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) 95%; -6.8 to 1.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2
	Estimation Comments	Confidence interval was only calculated for primary endpoint of the difference between avanafil and placebo, not for each individual arm.

5. Secondary Outcome

Title	Percentage of Subjects With Greater Than or Equal to 50% Reduction in Normal Sperm Morphology From Baseline to Week 26
Time Frame	baseline to week 26

Outcome Measure Data

Analysis Population Description

completers population

Arm/Group Title	Avanafil	Placebo
Arm/Group Description	100 mg once daily in the evening	placebo taken once daily in the evening
Measure Participants	68	69
Number [percentage of participants]	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Avanafil, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	If upper limit of 95% CI < 20% then avanafil is considered non-inferior to placebo.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; 0 to 0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0
	Estimation Comments	Confidence interval was only calculated for primary endpoint of the difference between avanafil and placebo, not for each individual arm.

Adverse Events

Arm/Group Title	Avanafil		Placebo
Arm/Group Description	100 mg once daily in the evening		placebo taken once daily in the evening
All Cause Mortality
	Avanafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Avanafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		1/91 (1.1%)
Renal and urinary disorders
Nephrolithiasis	0/90 (0%)	0	1/91 (1.1%)	1
Other (Not Including Serious) Adverse Events
	Avanafil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/90 (15.6%)		20/91 (22%)
Cardiac disorders
palpitations	0/90 (0%)	0	1/91 (1.1%)	1
Gastrointestinal disorders
abdominal discomfort	0/90 (0%)	0	2/91 (2.2%)	2
abdominal distension	1/90 (1.1%)	1	0/91 (0%)	0
dental caries	1/90 (1.1%)	1	0/91 (0%)	0
inguinal hernia	1/90 (1.1%)	1	0/91 (0%)	0
nausea	1/90 (1.1%)	1	1/91 (1.1%)	1
abdominal pain	0/90 (0%)	0	1/91 (1.1%)	1
diarrhoea	0/90 (0%)	0	1/91 (1.1%)	1
General disorders
pain	1/90 (1.1%)	1	0/91 (0%)	0
Infections and infestations
Nasopharyngitis	2/90 (2.2%)	2	2/91 (2.2%)	2
Tooth abscess	0/90 (0%)	0	2/91 (2.2%)	3
Bronchititis	1/90 (1.1%)	1	0/91 (0%)	0
rhinitis	1/90 (1.1%)	1	0/91 (0%)	0
upper respiratory tract infection	1/90 (1.1%)	1	0/91 (0%)	0
influenza	0/90 (0%)	0	1/91 (1.1%)	1
periodontitis	0/90 (0%)	0	1/91 (1.1%)	1
pilonidal cyst	0/90 (0%)	0	1/91 (1.1%)	1
urinary tract infection	0/90 (0%)	0	1/91 (1.1%)	1
Metabolism and nutrition disorders
decreased appetite	1/90 (1.1%)	1	0/91 (0%)	0
Musculoskeletal and connective tissue disorders
back pain	1/90 (1.1%)	1	1/91 (1.1%)	1
musculoskeletal discomfort	1/90 (1.1%)	1	0/91 (0%)	0
myalgia	1/90 (1.1%)	1	0/91 (0%)	0
pain in extremity	0/90 (0%)	0	1/91 (1.1%)	1
Nervous system disorders
Headache	3/90 (3.3%)	3	3/91 (3.3%)	7
hyperaesthesia	0/90 (0%)	0	1/91 (1.1%)	1
Psychiatric disorders
insomnia	1/90 (1.1%)	1	0/91 (0%)	0
anxiety	1/90 (1.1%)	1	0/91 (0%)	0
premature ejaculation	1/90 (1.1%)	1	0/91 (0%)	0
Renal and urinary disorders
nephrolithiasis	0/90 (0%)	0	1/91 (1.1%)	1
semenuria	0/90 (0%)	0	1/91 (1.1%)	1
urethral meatus stenosis	0/90 (0%)	0	1/91 (1.1%)	1
urinary retention	0/90 (0%)	0	1/91 (1.1%)	1
urinary straining	0/90 (0%)	0	1/91 (1.1%)	1
urine flow decreased	0/90 (0%)	0	1/91 (1.1%)	1
Reproductive system and breast disorders
penis disorder	0/90 (0%)	0	1/91 (1.1%)	1
testicular disorder	0/90 (0%)	0	1/91 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
nasal congestion	1/90 (1.1%)	1	2/91 (2.2%)	2
upper-airway cough syndrome	1/90 (1.1%)	1	0/91 (0%)	0
oropharyngeal pain	0/90 (0%)	0	1/91 (1.1%)	1
paranasal sinus hypersecretion	0/90 (0%)	0	1/91 (1.1%)	1
Skin and subcutaneous tissue disorders
acne	0/90 (0%)	0	1/91 (1.1%)	1
Vascular disorders
flushing	1/90 (1.1%)	1	0/91 (0%)	0
hot flush	1/90 (1.1%)	1	0/91 (0%)	0
hypertension	1/90 (1.1%)	1	0/91 (0%)	0

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.