Erectile Dysfunction, Metabolic Syndrome
Conditions
Keywords
Vardenafil, Erectile Dysfunction, Double-blind study
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)
Interventions
Vardenafil 10 mg tablets daily for 4 weeks, vardenafil 5 mg / 10 mg / 20 mg tablets for consecutive 4 weeks
DRUGPlacebo
Matching placebo tablets daily for 4 weeks, placebo tablets daily for consecutive 4 weeks
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 64 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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') |
| 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. |
| 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. |
| 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. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 75 |
| Placebo Matching placebo tablets PRN (pro re nata) for 4 weeks, placebo tablets PRN for consecutive 4 weeks | 72 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Non-compliant with study medication | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Vardenafil (Levitra, BAY38-9456) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 5.9 | 55.6 years STANDARD_DEVIATION 6.7 | 56.0 years STANDARD_DEVIATION 6.3 |
| BMI (body mass index) | 30.4 kg/m^2 STANDARD_DEVIATION 3.6 | 30.4 kg/m^2 STANDARD_DEVIATION 3.4 | 30.4 kg/m^2 STANDARD_DEVIATION 3.5 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 75 Participants | 72 Participants | 147 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 75 | 8 / 72 |
| serious Total, serious adverse events | 0 / 75 | 0 / 72 |
Outcome results
Primary
Change From Baseline in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Subscore at Week 8 or Last Observation Carried Forward (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.
Time frame: baseline and up to 8 weeks or LOCF
Population: Number of participants analyzed differs due to missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Change From Baseline in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Subscore at Week 8 or Last Observation Carried Forward (LOCF) | 20.96 Scores on a scale |
| Placebo | Change From Baseline in International Index of Erectile Function - Erectile Function Domain (IIEF-EF) Subscore at Week 8 or Last Observation Carried Forward (LOCF) | 14.20 Scores on a scale |
Comparison: ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpointp-value: <0.000195% CI: [-9.03, -4.49]ANCOVA
Primary
Change in Percentage From Baseline in Success of Erection Maintenance (SEP3: Sexual Encounter Profile Question 3) at Week 8
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
Population: Number of participants analyzed differs due to missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Change in Percentage From Baseline in Success of Erection Maintenance (SEP3: Sexual Encounter Profile Question 3) at Week 8 | 53.15 Percent erection maintenance |
| Placebo | Change in Percentage From Baseline in Success of Erection Maintenance (SEP3: Sexual Encounter Profile Question 3) at Week 8 | 27.00 Percent erection maintenance |
Comparison: ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpointp-value: <0.000195% CI: [-37.48, -14.83]ANCOVA
Primary
Change in Percentage From Baseline in Success of Penetration (SEP2: Sexual Encounter Profile Question 2) at Week 8
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
Population: Number of participants analyzed differs due to missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Change in Percentage From Baseline in Success of Penetration (SEP2: Sexual Encounter Profile Question 2) at Week 8 | 73.50 Percent successful penetrations |
| Placebo | Change in Percentage From Baseline in Success of Penetration (SEP2: Sexual Encounter Profile Question 2) at Week 8 | 52.79 Percent successful penetrations |
Comparison: ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpointp-value: <0.000195% CI: [-30.66, -10.76]ANCOVA
Secondary
Change in Percentage From Baseline in Ability to Ejaculate (SEP6) at Week 8
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
Population: Number of participants analyzed differs due to missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Change in Percentage From Baseline in Ability to Ejaculate (SEP6) at Week 8 | 71.29 Percent successful ejaculations |
| Placebo | Change in Percentage From Baseline in Ability to Ejaculate (SEP6) at Week 8 | 43.96 Percent successful ejaculations |
Comparison: ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpointp-value: <0.000195% CI: [-37.24, -17.43]ANCOVA
Secondary
Change in Percentage From Baseline in Ability to Obtain an Erection (SEP1) at Week 8
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
Population: Number of participants analyzed differs due to missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Change in Percentage From Baseline in Ability to Obtain an Erection (SEP1) at Week 8 | 91.36 Percent successful erections |
| Placebo | Change in Percentage From Baseline in Ability to Obtain an Erection (SEP1) at Week 8 | 75.79 Percent successful erections |
Comparison: ANCOVA, baseline covariate, endpoint week 8 or LOCF. Factors: treatment, pooled centers. Ls mean at endpointp-value: 0.000395% CI: [-23.8, -7.34]ANCOVA
Secondary
Number of Participants Who Can Stay on the Initially Provided Dosage of Vardenafil (10 mg PRN (Pro re Nata))
Number of participants with no recorded titration of Vardenafil after visit 3.
Time frame: week 4 and week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Number of Participants Who Can Stay on the Initially Provided Dosage of Vardenafil (10 mg PRN (Pro re Nata)) | 28 Participants |
| Placebo | Number of Participants Who Can Stay on the Initially Provided Dosage of Vardenafil (10 mg PRN (Pro re Nata)) | 13 Participants |
Secondary
Percentage of Participants Achieving Back to Normal Erectile Function at Week 8 or Last Observation Carried Forward (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')
Time frame: up to 8 weeks or LOCF
Population: Number of participants analyzed differs due to missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vardenafil (Levitra, BAY38-9456) | Percentage of Participants Achieving Back to Normal Erectile Function at Week 8 or Last Observation Carried Forward (LOCF) | 35 Percentage of participants |
| Placebo | Percentage of Participants Achieving Back to Normal Erectile Function at Week 8 or Last Observation Carried Forward (LOCF) | 10 Percentage of participants |
Comparison: Mantel-Haenszel Testp-value: 0.0004Mantel Haenszel