Study of Vardenafil in Patients Suffering From Erectile Dysfunction and Metabolic Syndrome

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00738400
• Collaborator: (none)
• Enrollment: 150
• Locations: 19
• Arms: 2
• Duration (Months): 11
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This is a controlled, randomized, multi-center prospective study of vardenafil to determine efficacy on Erectile Dysfunction (ED), tolerability and safety in men with ED and Metabolic Syndrome. This study will explore the rate of patients who do need to switch to the highest dosage based upon the expectation that most men can stay on vardenafil 10 mg PRN (pro re nata)

Condition or Disease	Intervention/Treatment	Phase
Erectile Dysfunction; Metabolic Syndrome	Drug: Vardenafil (Levitra, BAY38-9456); Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Double-blind, Placebo Controlled, Randomized Study of Vardenafil to Determine Efficacy on Erectile Dysfunction (ED) in Men With ED and Metabolic Syndrome (ED-METABOLIC)
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vardenafil (Levitra, BAY38-9456) Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Drug: Vardenafil (Levitra, BAY38-9456); Vardenafil 10 mg tablets daily for 4 weeks, vardenafil 5 mg / 10 mg / 20 mg tablets for consecutive 4 weeks
Placebo Comparator: Placebo Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks	Drug: Placebo; Matching placebo tablets daily for 4 weeks, placebo tablets daily for consecutive 4 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Subscore at Week 8 or Last Observation Carried Forward (LOCF) [baseline and up to 8 weeks or LOCF]

   The primary variable was the least square (LS)-mean difference between treatment groups in the IIEF-EF domain score (6-30 ordinal points, specifying the severity of erectile dysfunction: 6-10 'severe'; 11-16 'moderate'; 17-21 'mild to moderate'; 22-25 'mild'; 26-30 'no erectile dysfunction [ED]'). The target variable is the LS-mean difference between treatment groups at endpoint. The LS-means of both treatment groups are derived from a baseline-adjusted endpoint measure (week 8/last observation carried forward [LOCF]) as calculated via an ANCOVA.

2. Change in Percentage From Baseline in Success of Penetration (SEP2: Sexual Encounter Profile Question 2) at Week 8 [Baseline and 8 weeks]

   Percent successful penetrations were calculated per participant as the number of successful sexual attempts (penetrations) divided by the total number of attempts. The mean percent successful penetrations was then calculated across all participants.

3. Change in Percentage From Baseline in Success of Erection Maintenance (SEP3: Sexual Encounter Profile Question 3) at Week 8 [Baseline and 8 weeks]

   Percent successful maintenance of erection were calculated per participant as the number of successful attempts (maintenance of erection) divided by the total number of attempts. The mean percent successful maintenance of erection was then calculated across all participants.

Secondary Outcome Measures

1. Percentage of Participants Achieving "Back to Normal" Erectile Function at Week 8 or Last Observation Carried Forward (LOCF) [up to 8 weeks or LOCF]

   Responders: percentage of participants achieving an IIEF-EF score >25.(IIEF-EF domain score: 6-30 ordinal points, specifying the severity of erectile dysfunction: 6-10 'severe'; 11-16 'moderate'; 17-21 'mild to moderate'; 22-25 'mild'; 26-30 'no ED')

2. Change in Percentage From Baseline in Ability to Obtain an Erection (SEP1) at Week 8 [Baseline and 8 weeks]

   Percent successful erections were calculated per participant as the number of successful attempts (achievement of erection) divided by the total number of attempts. The mean percent successful erections was then calculated across all participants.

3. Change in Percentage From Baseline in Ability to Ejaculate (SEP6) at Week 8 [Baseline and 8 weeks]

   Percent successful ejaculations were calculated per participant as the number of successful attempts (achievement of ejaculation) divided by the total number of attempts. The mean percent successful ejaculations was then calculated across all participants.

4. Number of Participants Who Can Stay on the Initially Provided Dosage of Vardenafil (10 mg PRN (Pro re Nata)) [week 4 and week 8]

   Number of participants with no recorded titration of Vardenafil after visit 3.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Stable heterosexual relationship

• History of erectile dysfunction for at least 6 months

• IIEF- EF Domain entry score (at Visit 2): >21 points

• Documented metabolic syndrome according to the IDF (International Diabetes Foundation)

• Subjects motivated for erectile dysfunction treatment

• Documented, dated, written informed consent

Exclusion Criteria:

• Any underlying cardiovascular condition

• History of myocardial infarction

• Uncontrolled atrial fibrillation

• Resting hypotension

• Postural hypotension within 6 months of Visit 1

• History of congenital QT prolongation

• Bleeding disorder

• History of prostatectomy because of prostate cancer

• Hereditary degenerative retinal disorders

• History of loss of vision because of NAION (non-arteritic anterior ischemic optic neuropathy)

• 29 Additional Exclusion Criteria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Cham	Bayern	Germany	93413
2		Regensburg	Bayern	Germany	93055
3		Frankfurt	Hessen	Germany	60385
4		Marburg	Hessen	Germany	35039
5		Stuhr	Niedersachsen	Germany	28816
6		Bonn	Nordrhein-Westfalen	Germany	53119
7		Grevenbroich	Nordrhein-Westfalen	Germany	41515
8		Leverkusen	Nordrhein-Westfalen	Germany	51373
9		Mülheim	Nordrhein-Westfalen	Germany	45468
10		Wuppertal	Nordrhein-Westfalen	Germany	42103
11		Dierdorf	Rheinland-Pfalz	Germany	56269
12		Koblenz	Rheinland-Pfalz	Germany	56068
13		Trier	Rheinland-Pfalz	Germany	54290
14		Homburg	Saarland	Germany	66424
15		Dresden	Sachsen	Germany	01307
16		Leipzig	Sachsen	Germany	04109
17		Berlin		Germany	12107
18		Berlin		Germany	14197
19		Hamburg		Germany	20354

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00738400
• Other Study ID Numbers: 13171; 2008-002140-41; ED-METABOLIC
• First Posted: Aug 20, 2008
• Last Update Posted: Nov 16, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Bayer: Vardenafil; Erectile Dysfunction; Double-blind study
• Additional relevant MeSH terms: Erectile Dysfunction; Metabolic Syndrome; Syndrome; Vardenafil Dihydrochloride

Study Results

Participant Flow

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
Period Title: Overall Study
STARTED	76	74
Received Treatment, Safety Population	75	72
ITT (Intent To Treatment) Population	75	70
COMPLETED	72	67
NOT COMPLETED	4	7

Baseline Characteristics

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo	Total
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks	Total of all reporting groups
Overall Participants	75	72	147
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.3 (5.9)	55.6 (6.7)	56.0 (6.3)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	75 100%	72 100%	147 100%
BMI (body mass index) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	30.4 (3.6)	30.4 (3.4)	30.4 (3.5)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Subscore at Week 8 or Last Observation Carried Forward (LOCF)
Description	The primary variable was the least square (LS)-mean difference between treatment groups in the IIEF-EF domain score (6-30 ordinal points, specifying the severity of erectile dysfunction: 6-10 'severe'; 11-16 'moderate'; 17-21 'mild to moderate'; 22-25 'mild'; 26-30 'no erectile dysfunction [ED]'). The target variable is the LS-mean difference between treatment groups at endpoint. The LS-means of both treatment groups are derived from a baseline-adjusted endpoint measure (week 8/last observation carried forward [LOCF]) as calculated via an ANCOVA.
Time Frame	baseline and up to 8 weeks or LOCF

Outcome Measure Data

Analysis Population Description

Number of participants analyzed differs due to missing data.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
Measure Participants	74	70
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	20.96	14.20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpoint
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.76
	Confidence Interval	() 95%; -9.03 to -4.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change in Percentage From Baseline in Success of Penetration (SEP2: Sexual Encounter Profile Question 2) at Week 8
Description	Percent successful penetrations were calculated per participant as the number of successful sexual attempts (penetrations) divided by the total number of attempts. The mean percent successful penetrations was then calculated across all participants.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analyzed differs due to missing data.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
Measure Participants	73	64
Least Squares Mean (95% Confidence Interval) [Percent successful penetrations]	73.50	52.79

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpoint
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-20.71
	Confidence Interval	() 95%; -30.66 to -10.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Change in Percentage From Baseline in Success of Erection Maintenance (SEP3: Sexual Encounter Profile Question 3) at Week 8
Description	Percent successful maintenance of erection were calculated per participant as the number of successful attempts (maintenance of erection) divided by the total number of attempts. The mean percent successful maintenance of erection was then calculated across all participants.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analyzed differs due to missing data.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
Measure Participants	73	64
Least Squares Mean (95% Confidence Interval) [Percent erection maintenance]	53.15	27.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpoint
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-26.16
	Confidence Interval	() 95%; -37.48 to -14.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants Achieving "Back to Normal" Erectile Function at Week 8 or Last Observation Carried Forward (LOCF)
Description	Responders: percentage of participants achieving an IIEF-EF score >25.(IIEF-EF domain score: 6-30 ordinal points, specifying the severity of erectile dysfunction: 6-10 'severe'; 11-16 'moderate'; 17-21 'mild to moderate'; 22-25 'mild'; 26-30 'no ED')
Time Frame	up to 8 weeks or LOCF

Outcome Measure Data

Analysis Population Description

Number of participants analyzed differs due to missing data.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
Measure Participants	74	70
Number [Percentage of participants]	35 46.7%	10 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	Mantel-Haenszel Test
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mantel Haenszel
	Comments

5. Secondary Outcome

Title	Change in Percentage From Baseline in Ability to Obtain an Erection (SEP1) at Week 8
Description	Percent successful erections were calculated per participant as the number of successful attempts (achievement of erection) divided by the total number of attempts. The mean percent successful erections was then calculated across all participants.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analyzed differs due to missing data.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
Measure Participants	73	64
Least Squares Mean (95% Confidence Interval) [Percent successful erections]	91.36	75.79

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpoint
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.57
	Confidence Interval	() 95%; -23.80 to -7.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change in Percentage From Baseline in Ability to Ejaculate (SEP6) at Week 8
Description	Percent successful ejaculations were calculated per participant as the number of successful attempts (achievement of ejaculation) divided by the total number of attempts. The mean percent successful ejaculations was then calculated across all participants.
Time Frame	Baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Number of participants analyzed differs due to missing data.

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
Measure Participants	73	64
Least Squares Mean (95% Confidence Interval) [Percent successful ejaculations]	71.29	43.96

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vardenafil (Levitra, BAY38-9456), Placebo
	Comments	ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpoint
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-27.33
	Confidence Interval	() 95%; -37.24 to -17.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants Who Can Stay on the Initially Provided Dosage of Vardenafil (10 mg PRN (Pro re Nata))
Description	Number of participants with no recorded titration of Vardenafil after visit 3.
Time Frame	week 4 and week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)	Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks	Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
Measure Participants	75	70
Number [Participants]	28 37.3%	13 18.1%

Adverse Events

Arm/Group Title	Vardenafil (Levitra, BAY38-9456)		Placebo
Arm/Group Description	Vardenafil 10 mg tablets PRN (pro re nata) for 4 weeks, Vardenafil 5 mg/10 mg/20 mg tablets PRN for consecutive 4 weeks		Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks
All Cause Mortality
	Vardenafil (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vardenafil (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/72 (0%)
Other (Not Including Serious) Adverse Events
	Vardenafil (Levitra, BAY38-9456)		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/75 (21.3%)		8/72 (11.1%)
Cardiac disorders
Arrhythmia	1/75 (1.3%)	1	0/72 (0%)	0
Ear and labyrinth disorders
Tinnitus	0/75 (0%)	0	1/72 (1.4%)	1
Gastrointestinal disorders
Diarrhoea	0/75 (0%)	0	1/72 (1.4%)	1
Nausea	0/75 (0%)	0	2/72 (2.8%)	2
Reflux oesophagitis	1/75 (1.3%)	1	0/72 (0%)	0
Infections and infestations
Abscess	1/75 (1.3%)	1	0/72 (0%)	0
Balanitis candida	0/75 (0%)	0	1/72 (1.4%)	1
Nasopharyngitis	3/75 (4%)	3	1/72 (1.4%)	1
Metabolism and nutrition disorders
Diabetes mellitus	0/75 (0%)	0	1/72 (1.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/75 (2.7%)	2	0/72 (0%)	0
Pain in extremity	1/75 (1.3%)	1	0/72 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/75 (0%)	0	1/72 (1.4%)	1
Nervous system disorders
Headache	7/75 (9.3%)	13	1/72 (1.4%)	1
Psychiatric disorders
Depression	0/75 (0%)	0	1/72 (1.4%)	1
Premature ejaculation	1/75 (1.3%)	1	0/72 (0%)	0
Reproductive system and breast disorders
Balanitis	1/75 (1.3%)	1	0/72 (0%)	0
Vascular disorders
Flushing	1/75 (1.3%)	4	0/72 (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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.