Safety Study Looking at the Effects of Stendra on Vision

• Sponsor: VIVUS LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02033200
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to see if Stendra causes any changes in vision, eye pressure, pupil dilation, and color vision in healthy males.

Condition or Disease	Intervention/Treatment	Phase
Vision	Drug: Stendra 200 mg; Drug: Placebo	Phase 4

Detailed Description

The objectives of this study are to assess the effect of Stendra on visual acuity, intraocular pressure, pupillometry, and color vision discrimination in healthy male subjects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Placebo-Controlled, Single-Dose, Parallel Study to Assess the Effects of Avanafil (STENDRA™) on Multiple Parameters of Vision, Including, But Not Limited to Visual Acuity, Intraocular Pressure, Pupillometry, and Color Vision Discrimination, in Healthy Male Subjects
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Stendra 200 mg	Drug: Stendra 200 mg; Other Names: avanafil ; Drug: Placebo
Placebo Comparator: Placebo placebo	Drug: Stendra 200 mg; Other Names: avanafil ; Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Color Vision Discrimination 1 Hour Post Dosing [1 hour]

   Color vision discrimination was performed using the Lanthony 40-Hue Test according to Farnsworth-Munsell 100-Hue Test. The total error score was derived by counting the number of caps misplaced.

2. Change From Baseline in Visual Acuity 1 Hour Post Dosing [1 hour]

   Visual acuity was measured using the Logarithm of the Minimum Angle Resolution (LogMAR) chart. The LogMAR value of the best line read was noted and the number of letters read in the next row was multiplied by 0.02, then subtracted from the LogMAR value of the best line completely read.

3. Change From Baseline in Pupil Dilation 1 Hour Post Dosing [1 hour]

   Pupil dilation was measured using the Neuroptics Model VIP 200 pupillometer under standard lighting conditions.

4. Change From Baseline in Intraocular Pressure 1 Hour Post Dosing [1 hour]

   Intraocular Pressure was measured using the Goldman applanation tonometry

Secondary Outcome Measures

1. Change From Baseline in Visual Acuity 24 Hours Post Dosing [24 hours]

2. Change From Baseline in Pupil Dilation 24 Hour Post Dosing [24 hour]

3. Change From Baseline in Color Vision Discrimination 24 Hour Post Dosing [24 hours]

4. Change From Baseline in Intraocular Pressure 24 Hour Post Dosing [24 hours]

   Intraocular pressure was measuring using the Goldman applanation tonometry

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Healthy adult males 18 to 45 years of age, inclusive

• Non-tobacco user for at least 6 months prior to first dose

Exclusion Criteria:

• History or presence of retinal disease or any vision defects including color vision

• Intraocular pressure value ≥ 22mm Hg

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

• Systolic blood pressure < 90 or > 140 mm Hg or Diastolic blood pressure < 50 or >90 mm Hg (3 rechecks)

• Initiation or change in dose of any α-blockers 14 days prior to randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Celerion Inc	Tempe	Arizona	United States	85283

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: NCT02033200
• Other Study ID Numbers: TA-402
• First Posted: Jan 10, 2014
• Last Update Posted: Mar 13, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by VIVUS LLC: vision; Stendra; avanafil; PDE5 inhibitor; visual acuity; intraocular pressure; pupillometry; color vision discrimination; healthy males

Study Results

Participant Flow

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Period Title: Overall Study
STARTED	40	40
COMPLETED	40	40
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Active	Placebo	Total
Arm/Group Description	Stendra 200 mg	placebo	Total of all reporting groups
Overall Participants	40	40	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.9 (7.67)	35.1 (7.67)	35.0 (7.62)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	40 100%	40 100%	80 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	32 80%	34 85%	66 82.5%
Not Hispanic or Latino	8 20%	6 15%	14 17.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 5%	1 2.5%	3 3.8%
Asian	1 2.5%	0 0%	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 10%	3 7.5%	7 8.8%
White	33 82.5%	35 87.5%	68 85%
More than one race	0 0%	1 2.5%	1 1.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	40 100%	40 100%	80 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Color Vision Discrimination 1 Hour Post Dosing
Description	Color vision discrimination was performed using the Lanthony 40-Hue Test according to Farnsworth-Munsell 100-Hue Test. The total error score was derived by counting the number of caps misplaced.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Measure Participants	40	40
Right eye	0.1 (1.98)	-0.4 (2.37)
Left eye	-0.2 (1.70)	-0.5 (1.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size had enough power to detect any meaningful difference between treatment groups in the right eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8216
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.076
	Confidence Interval	(2-Sided) 95%; -0.592 to 0.744
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.335
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size had adequate power to detect a meaningful difference between treatment groups in the left eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.324
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.257
	Confidence Interval	(2-Sided) 95%; -0.258 to 0.771
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.258
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Visual Acuity 1 Hour Post Dosing
Description	Visual acuity was measured using the Logarithm of the Minimum Angle Resolution (LogMAR) chart. The LogMAR value of the best line read was noted and the number of letters read in the next row was multiplied by 0.02, then subtracted from the LogMAR value of the best line completely read.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Measure Participants	40	40
Right Eye	-0.014 (0.0641)	-0.023 (0.0694)
Left Eye	-0.042 (0.0809)	-0.011 (0.0836)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size provided enough power to detect any meaningful difference between the two treatment groups in the right eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7864
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.004
	Confidence Interval	(2-Sided) 95%; -0.024 to 0.031
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.014
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size provided enough power to detect any meaningful difference between the two treatment groups in the left eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1953
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means difference
	Estimated Value	-0.022
	Confidence Interval	(2-Sided) 95%; -0.056 to 0.012
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.017
	Estimation Comments

3. Primary Outcome

Title	Change From Baseline in Pupil Dilation 1 Hour Post Dosing
Description	Pupil dilation was measured using the Neuroptics Model VIP 200 pupillometer under standard lighting conditions.
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Measure Participants	40	40
Right eye	-0.14 (0.280)	0.02 (0.270)
Left eye	-0.19 (0.264)	-0.10 (0.285)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size provided enough power to detect any meaningful difference between the two treatment groups in the right eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0101
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.160
	Confidence Interval	(2-Sided) 95%; -0.280 to -0.039
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.061
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size provided enough power to detect any meaningful difference between the two treatment groups in the left eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1583
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.087
	Confidence Interval	(2-Sided) 95%; -0.209 to 0.035
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.061
	Estimation Comments

4. Primary Outcome

Title	Change From Baseline in Intraocular Pressure 1 Hour Post Dosing
Description	Intraocular Pressure was measured using the Goldman applanation tonometry
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Measure Participants	40	40
Right eye	0.03 (1.761)	0.29 (1.609)
Left eye	0.36 (1.860)	-0.26 (1.335)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size should provide approximately 90% power to detect a 1.6 mmHg difference in the mean change in Intraocular Pressure between the two treatment groups in the right eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9324
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.031
	Confidence Interval	(2-Sided) 95%; -0.746 to 0.685
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.359
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size should provide approximately 90% power to detect a 1.6 mmHg difference in the mean change in intraocular pressure between the two treatment groups in the left eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0343
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.751
	Confidence Interval	(2-Sided) 95%; 0.057 to 1.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.348
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Visual Acuity 24 Hours Post Dosing
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Measure Participants	40	40
Right eye	-0.012 (0.0682)	-0.035 (0.0920)
Left eye	-0.027 (0.1042)	-0.020 (0.0908)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size had enough power to detect any meaningful difference between treatment groups in the right eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3139
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means difference
	Estimated Value	0.017
	Confidence Interval	(2-Sided) 95%; -0.017 to 0.051
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.017
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size had enough power to detect any meaningful difference between treatment groups in the left eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9334
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.002
	Confidence Interval	(2-Sided) 95%; -0.045 to 0.042
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Pupil Dilation 24 Hour Post Dosing
Time Frame	24 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Measure Participants	40	40
Right eye	0.0 (0.238)	-0.02 (0.249)
Left eye	-0.06 (0.223)	-0.07 (0.289)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size had enough power to detect any meaningful difference between treatment groups in the right eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7723
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.016
	Confidence Interval	(2-Sided) 95%; -0.093 to 0.125
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.055
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size had enough power to detect any meaningful difference between treatment groups in the left eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9107
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.007
	Confidence Interval	(2-Sided) 95%; -0.109 to 0.122
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.058
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Color Vision Discrimination 24 Hour Post Dosing
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Measure Participants	40	40
Right eye	-0.1 (1.66)	-0.4 (2.49)
Left eye	-0.2 (1.69)	-0.1 (2.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size had enough power to detect any meaningful difference between treatment groups in the right eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7787
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Means difference
	Estimated Value	-0.078
	Confidence Interval	(2-Sided) 95%; -0.632 to 0.475
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.278
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size had enough power to detect any meaningful difference between treatment groups in the left eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6013
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	-0.180
	Confidence Interval	(2-Sided) 95%; -0.865 to 0.504
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.344
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Intraocular Pressure 24 Hour Post Dosing
Description	Intraocular pressure was measuring using the Goldman applanation tonometry
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	Stendra 200 mg	placebo
Measure Participants	40	40
Right eye	-0.10 (2.176)	0.03 (1.423)
Left eye	0.03 (1.694)	-0.09 (1.339)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size should provide approximately 90% power to detect a 1.6 mmHg difference in the mean change in IOP between the two treatment groups in the right eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8209
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.091
	Confidence Interval	(2-Sided) 95%; -0.705 to 0.887
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.400
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Active, Placebo
	Comments	The sample size should provide approximately 90% power to detect a 1.6 mmHg difference in the mean change in IOP between the two treatment groups in the left eye.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4931
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS means difference
	Estimated Value	0.227
	Confidence Interval	(2-Sided) 95%; -0.430 to 0.884
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.330
	Estimation Comments

Adverse Events

Arm/Group Title	Active		Placebo
Arm/Group Description	Stendra 200 mg		placebo
All Cause Mortality
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/40 (40%)		2/40 (5%)
Gastrointestinal disorders
abdomonial pain	2/40 (5%)	2	0/40 (0%)	0
diarrhea	2/40 (5%)	2	0/40 (0%)	0
nausea	3/40 (7.5%)	3	0/40 (0%)	0
vomiting	2/40 (5%)	2	0/40 (0%)	0
General disorders
feeling hot	2/40 (5%)	2	0/40 (0%)	0
Investigations
alanine aminotransferase increased	1/40 (2.5%)	1	0/40 (0%)	0
aspartate aminotransferase increased	1/40 (2.5%)	1	0/40 (0%)	0
blood creatine phosphokinase increased	2/40 (5%)	2	0/40 (0%)	0
blood lactate dehydrogenase increased	1/40 (2.5%)	1	0/40 (0%)	0
blood urine present	1/40 (2.5%)	1	0/40 (0%)	0
protein urine present	1/40 (2.5%)	1	0/40 (0%)	0
red blood cells urine	2/40 (5%)	2	0/40 (0%)	0
Musculoskeletal and connective tissue disorders
arthralgia	1/40 (2.5%)	1	0/40 (0%)	0
myalgia	1/40 (2.5%)	1	0/40 (0%)	0
neck pain	1/40 (2.5%)	1	0/40 (0%)	0
Nervous system disorders
dysgeusia	0/40 (0%)	0	1/40 (2.5%)	1
headache	10/40 (25%)	10	1/40 (2.5%)	1
Psychiatric disorders
libido increased	1/40 (2.5%)	1	0/40 (0%)	0
Respiratory, thoracic and mediastinal disorders
nasal congestion	2/40 (5%)	2	0/40 (0%)	0
Vascular disorders
flushing	1/40 (2.5%)	1	0/40 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.