Erectile Dysfunction
Conditions
Keywords
Erectile Dysfunction, ED, Impotence
Brief summary
The purpose of this trial is to evaluate if treatment with tadalafil once daily will allow men to return to normal erectile function in those who did not have normal erectile function following as-needed (PRN) Phosphodiesterase Type 5 (PDE5) Inhibitor treatment.
Interventions
DRUGTadalafil
Administer orally
DRUGPlacebo
Administer orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least a 3-month history of erectile dysfunction (ED). * Are able to read, understand and provide signed informed consent. * Have an International Index of Erectile Function-Erectile Function (IIEF-EF) domain score that is greater than or equal to 17 and less than 26 at screening. * Have been taking a maximum dose of sildenafil citrate (100 milligram \[mg\]), vardenafil (20 mg), or tadalafil (20 mg) on as needed basis for at least one month prior to screening. * Anticipate having the same female sexual partner during the study who is willing to participate in the required number of sexual intercourse attempts and complete study measures during the study. * Agree to make at least four sexual intercourse attempts during both the 4-week as needed run-in period and the 4-week non-drug run-in period. * Agree not to use any other erectile dysfunction (ED) treatment, including herbal therapy during the 4-week non-drug, run-in, the double-blind treatment period, the open label period and for 96 hours after the end of the study. Partner Inclusion Criteria: * Are female and at least 18 years of age at screening. * Anticipate having the same male study subject as her sexual partner during the study. * Able to read, understand and provide signed informed consent. * Agree to make the required number of sexual intercourse attempts with the male sexual study partner during the study. * Willing to participate in recording responses to the treatment satisfaction scale.
Exclusion criteria
* Have an IIEF-EF domain score of greater than or equal to 26 at screening. * Prior ineffective treatment with (or nonresponder to) any PDE5 Inhibitor * Have previously used or are currently using any PDE5 inhibitor once daily. * Present with ED caused by other primary disorders or ED caused by untreated/inadequately treated endocrine disease. * Partner unwilling to complete all study requirements. * History of radical prostatectomy or other pelvic surgery or penile implant, or a clinically significant penile deformity, in the opinion of the investigator * Exhibit evidence of clinically significant renal insufficiency or hepatobiliary disease, or significant cardiac history as determined by the investigator * Currently receive treatment with nitrates, cancer chemotherapy, or antiandrogens * Have previously completed or withdrawn from this study or any other study investigating tadalafil for once-daily use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Having an International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 Through 12-Week Endpoint (Double-Blind Treatment Period) | Baseline through 12 weeks | Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function. Data presented are the percentage of participants who return to normal erectile function (IIEF-EF domain score ≥26) at end of double-blind treatment period (Period III). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Intercourse Satisfaction (IIEF-IS) Domain Score | Baseline, 12 weeks | Self-reported intercourse satisfaction over the past 4 weeks. IIEF-IS is the sum of Questions 6, 7 and 8 of the IIEF. Scores range from 0 (low/no satisfaction) to 5 (high satisfaction) for each question, with the total possible score for the 3 questions of 0 to 15. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. |
| Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Overall Satisfaction (IIEF-OS) Domain Score | Baseline, 12 weeks | Self-reported overall satisfaction over the past 4 weeks. IIEF-OS is the sum of Questions 13 and 14; each question scored as 1 (low/no satisfaction) through 5 (high satisfaction) with total subscore for the 2 questions of 2 to 10. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. |
| Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Baseline, 12 weeks | Assessed was the mean change from baseline in the percentage of Yes responses to the SEP diary Questions 1-5. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. |
| Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Baseline, 12 weeks | The TSS measured participant satisfaction with treatment based on a 13-item questionnaire. The overall score for each of five TSS domains (confidence to complete sexual activity, ease of erection, pleasure from sexual activity, erectile function satisfaction, and satisfaction with orgasm) was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. |
| Treatment Satisfaction Scale (TSS) - Patient Satisfaction With Medication Score at Week 12 Endpoint | Week 12 | The TSS - patient satisfaction with medication measured participant satisfaction with treatment based on a 13-item questionnaire. The overall score was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Satisfaction with medication was analyzed using analysis of covariance (ANOVA). The model included factors of study, treatment group, and pooled site within study. |
| Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | Baseline, 12 weeks | Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. |
| Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Baseline, 12 weeks | The TSS measured participant's partner satisfaction with treatment based on a 13-item questionnaire. The overall score for each of five TSS domains (confidence to complete sexual activity, ease of erection, pleasure from sexual activity, erectile function satisfaction, and satisfaction with orgasm) was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. |
| Treatment Satisfaction Scale (TSS) - Partner Satisfaction With Medication Score at Week 12 Endpoint | Week 12 | The TSS - partner satisfaction with medication measured participant's partner satisfaction with treatment based on a 13-item questionnaire. The overall score was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Satisfaction with medication was analyzed using analysis of covariance (ANOVA). The model included factors of study, treatment group, and pooled site within study. |
| Percentage of Participants Having International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 From 12 to 16 Weeks | 12 weeks through 16 weeks | Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function. Data presented are the percentage of participants who return to normal erectile function (IIEF-EF domain score ≥26) at end of open-label extension treatment period (Period IV). |
| Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | 12 weeks and 16 weeks | Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function. |
| Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3 | 12 weeks and 16 weeks | Assessed the percentage of Yes responses to the SEP diary Question 3 Did your erection last long enough for you to have successful intercourse? from Week 12 (end of double-Blind treatment) to Week 16 (end of open-label treatment). |
| Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function (IIEF) Question 15 (Sexual Confidence) | Baseline, 12 weeks | Self-reported erectile function over the past 4 weeks. Question 15, confidence in the ability to get an erection, is scored from 1 (very low confidence) to 5 (very high confidence). Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction. |
Countries
Canada, United States
Participant flow
Pre-assignment details
This study consisted of 4 periods. Period I was a 4-week, as needed, run-in period. Period II was a 4-week, non-drug, wash-out period. Period III was a 12-week (Weeks 0-12), double-blind treatment. Period IV was a 4-week (Weeks 13-16), open-label treatment extension. Only participants completing Period III were eligible to continue into Period IV.
Participants by arm
| Arm | Count |
|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil 2.5 milligram (mg) Tadalafil for 4 weeks, followed by 5 mg Tadalafil for 8 weeks during double-blind treatment period. | 207 |
| 5 mg Tadalafil 5.0 mg Tadalafil for 12 weeks during double-blind treatment period. | 207 |
| Placebo Placebo for 12 weeks during double-blind treatment period. | 209 |
| Total | 623 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period III (Weeks 0-12) | Adverse Event | 3 | 3 | 2 | 0 |
| Period III (Weeks 0-12) | Entry Criteria Not Met | 4 | 2 | 4 | 0 |
| Period III (Weeks 0-12) | Lack of Efficacy | 2 | 0 | 1 | 0 |
| Period III (Weeks 0-12) | Lost to Follow-up | 2 | 2 | 3 | 0 |
| Period III (Weeks 0-12) | Protocol Violation | 0 | 0 | 1 | 0 |
| Period III (Weeks 0-12) | Sponsor Decision | 3 | 4 | 2 | 0 |
| Period III (Weeks 0-12) | Withdrawal by Subject | 7 | 7 | 6 | 0 |
| Period IV (Weeks 13-16) | Adverse Event | 0 | 0 | 0 | 1 |
| Period IV (Weeks 13-16) | Entry Criteria Not Met | 0 | 0 | 0 | 1 |
| Period IV (Weeks 13-16) | Lost to Follow-up | 0 | 0 | 0 | 5 |
| Period IV (Weeks 13-16) | Withdrawal by Subject | 0 | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | 2.5 mg Titrated to 5 mg Tadalafil | 5 mg Tadalafil | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 57.3 years STANDARD_DEVIATION 10.68 | 58.1 years STANDARD_DEVIATION 10.36 | 57.6 years STANDARD_DEVIATION 10.17 | 57.6 years STANDARD_DEVIATION 10.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 10 Participants | 9 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 199 Participants | 197 Participants | 200 Participants | 596 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 24 Participants | 35 Participants | 88 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 173 Participants | 177 Participants | 167 Participants | 517 Participants |
| Region of Enrollment Canada | 8 participants | 11 participants | 18 participants | 37 participants |
| Region of Enrollment Puerto Rico | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 199 participants | 195 participants | 191 participants | 585 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 207 Participants | 207 Participants | 209 Participants | 623 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 46 / 205 | 68 / 205 | 50 / 207 | 23 / 546 |
| serious Total, serious adverse events | 1 / 205 | 1 / 205 | 1 / 207 | 3 / 546 |
Outcome results
Primary
Percentage of Participants Having an International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 Through 12-Week Endpoint (Double-Blind Treatment Period)
Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function. Data presented are the percentage of participants who return to normal erectile function (IIEF-EF domain score ≥26) at end of double-blind treatment period (Period III).
Time frame: Baseline through 12 weeks
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline IIEF-EF measurement, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Percentage of Participants Having an International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 Through 12-Week Endpoint (Double-Blind Treatment Period) | 38.7 percentage of participants |
| 5 mg Tadalafil (Period III) | Percentage of Participants Having an International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 Through 12-Week Endpoint (Double-Blind Treatment Period) | 39.6 percentage of participants |
| Placebo (Period III) | Percentage of Participants Having an International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 Through 12-Week Endpoint (Double-Blind Treatment Period) | 12.1 percentage of participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score
Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function.
Time frame: 12 weeks and 16 weeks
Population: All participants who were entered the open-label treatment, received at least 1 dose of study drug during open-label treatment, had Week 12 and at least 1 IIEF-EF measurement during open-label treatment, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | End of Week 12 | 22.4 units on a scale | Standard Deviation 6.71 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | End of Week 16 | 24.1 units on a scale | Standard Deviation 6.44 |
| 5 mg Tadalafil (Period III) | Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | End of Week 12 | 22.5 units on a scale | Standard Deviation 7.07 |
| 5 mg Tadalafil (Period III) | Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | End of Week 16 | 24.2 units on a scale | Standard Deviation 6.46 |
| Placebo (Period III) | Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | End of Week 12 | 16.0 units on a scale | Standard Deviation 7.39 |
| Placebo (Period III) | Change From 12 Weeks to 16 Weeks in Participant's International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | End of Week 16 | 24.4 units on a scale | Standard Deviation 6.73 |
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
p-value: <0.001Paired t-test
Secondary
Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score
Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction.
Time frame: Baseline, 12 weeks
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline IIEF-EF measurement, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | 7.9 units on a scale | Standard Error 0.49 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | 8.1 units on a scale | Standard Error 0.49 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score | 1.8 units on a scale | Standard Error 0.49 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function (IIEF) Question 15 (Sexual Confidence)
Self-reported erectile function over the past 4 weeks. Question 15, confidence in the ability to get an erection, is scored from 1 (very low confidence) to 5 (very high confidence). Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction.
Time frame: Baseline, 12 weeks
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline IIEF question 15 (Sexual Confidence) assessment, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function (IIEF) Question 15 (Sexual Confidence) | 1.2 units on a scale | Standard Error 0.08 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function (IIEF) Question 15 (Sexual Confidence) | 1.3 units on a scale | Standard Error 0.08 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function (IIEF) Question 15 (Sexual Confidence) | 0.3 units on a scale | Standard Error 0.08 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Intercourse Satisfaction (IIEF-IS) Domain Score
Self-reported intercourse satisfaction over the past 4 weeks. IIEF-IS is the sum of Questions 6, 7 and 8 of the IIEF. Scores range from 0 (low/no satisfaction) to 5 (high satisfaction) for each question, with the total possible score for the 3 questions of 0 to 15. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction.
Time frame: Baseline, 12 weeks
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline IIEF-IS measurement, excluding those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Intercourse Satisfaction (IIEF-IS) Domain Score | 2.8 units on a scale | Standard Error 0.21 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Intercourse Satisfaction (IIEF-IS) Domain Score | 2.6 units on a scale | Standard Error 0.21 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Intercourse Satisfaction (IIEF-IS) Domain Score | 0.6 units on a scale | Standard Error 0.21 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Overall Satisfaction (IIEF-OS) Domain Score
Self-reported overall satisfaction over the past 4 weeks. IIEF-OS is the sum of Questions 13 and 14; each question scored as 1 (low/no satisfaction) through 5 (high satisfaction) with total subscore for the 2 questions of 2 to 10. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction.
Time frame: Baseline, 12 weeks
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline IIEF-OS measurement, excluding those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Overall Satisfaction (IIEF-OS) Domain Score | 2.4 units on a scale | Standard Error 0.16 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Overall Satisfaction (IIEF-OS) Domain Score | 2.4 units on a scale | Standard Error 0.16 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in the International Index of Erectile Function - Overall Satisfaction (IIEF-OS) Domain Score | 0.6 units on a scale | Standard Error 0.16 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner
The TSS measured participant's partner satisfaction with treatment based on a 13-item questionnaire. The overall score for each of five TSS domains (confidence to complete sexual activity, ease of erection, pleasure from sexual activity, erectile function satisfaction, and satisfaction with orgasm) was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction.
Time frame: Baseline, 12 weeks
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline partner's TSS measurement, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Erectile function satisfaction | 28.6 units on a scale | Standard Error 1.84 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Pleasure from sexual activity | 18.2 units on a scale | Standard Error 1.69 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Confidence to complete sexual activity | 23.7 units on a scale | Standard Error 2.01 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Ease of erection | 23.1 units on a scale | Standard Error 1.76 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Satisfaction with orgasm | 18.7 units on a scale | Standard Error 2.06 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Pleasure from sexual activity | 18.5 units on a scale | Standard Error 1.68 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Confidence to complete sexual activity | 27.2 units on a scale | Standard Error 1.99 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Ease of erection | 25.3 units on a scale | Standard Error 1.75 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Erectile function satisfaction | 28.5 units on a scale | Standard Error 1.83 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Satisfaction with orgasm | 21.0 units on a scale | Standard Error 2.05 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Satisfaction with orgasm | 3.6 units on a scale | Standard Error 2.04 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Erectile function satisfaction | 3.4 units on a scale | Standard Error 1.83 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Confidence to complete sexual activity | 2.0 units on a scale | Standard Error 1.99 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Pleasure from sexual activity | 1.3 units on a scale | Standard Error 1.68 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Partner | Ease of erection | 0.7 units on a scale | Standard Error 1.75 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient
The TSS measured participant satisfaction with treatment based on a 13-item questionnaire. The overall score for each of five TSS domains (confidence to complete sexual activity, ease of erection, pleasure from sexual activity, erectile function satisfaction, and satisfaction with orgasm) was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction.
Time frame: Baseline, 12 weeks
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline TSS measurement, excluding those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Erectile function satisfaction | 31.0 units on a scale | Standard Error 1.82 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Pleasure from sexual activity | 22.6 units on a scale | Standard Error 1.58 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Confidence to complete sexual activity | 27.0 units on a scale | Standard Error 1.78 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Ease of erection | 24.0 units on a scale | Standard Error 1.69 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Satisfaction with orgasm | 25.6 units on a scale | Standard Error 1.9 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Pleasure from sexual activity | 22.7 units on a scale | Standard Error 1.58 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Confidence to complete sexual activity | 29.2 units on a scale | Standard Error 1.78 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Ease of erection | 24.7 units on a scale | Standard Error 1.69 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Erectile function satisfaction | 33.6 units on a scale | Standard Error 1.81 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Satisfaction with orgasm | 26.3 units on a scale | Standard Error 1.89 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Satisfaction with orgasm | 6.2 units on a scale | Standard Error 1.88 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Erectile function satisfaction | 4.9 units on a scale | Standard Error 1.81 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Confidence to complete sexual activity | 3.8 units on a scale | Standard Error 1.77 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Pleasure from sexual activity | 3.3 units on a scale | Standard Error 1.57 |
| Placebo (Period III) | Change From Baseline to 12-Week Endpoint in Treatment Satisfaction Scale (TSS) - Patient | Ease of erection | 4.1 units on a scale | Standard Error 1.68 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5
Assessed was the mean change from baseline in the percentage of Yes responses to the SEP diary Questions 1-5. Least Squares (LS) mean of the change from baseline to endpoint is from an analysis of covariance (ANCOVA). The model included centered-baseline as a covariate and factors of study, treatment group, and pooled site within study, and centered-baseline-by-treatment-group interaction.
Time frame: Baseline, 12 weeks
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline SEP Questions assessment, excluding those with International Index of Erectile Function - Erectile Function (IIEF-EF) domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 4: Satisfied with Hardness | 44.2 percentage of yes responses | Standard Error 2.73 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 3: Successful Intercourse | 37.3 percentage of yes responses | Standard Error 2.52 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 1: Able to Achieve Erection | 12.2 percentage of yes responses | Standard Error 1.63 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 2: Able to Insert | 26.2 percentage of yes responses | Standard Error 2.25 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 5: Overall Satisfaction with Experience | 43.6 percentage of yes responses | Standard Error 2.7 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 3: Successful Intercourse | 39.4 percentage of yes responses | Standard Error 2.5 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 1: Able to Achieve Erection | 11.4 percentage of yes responses | Standard Error 1.62 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 2: Able to Insert | 26.1 percentage of yes responses | Standard Error 2.23 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 4: Satisfied with Hardness | 42.8 percentage of yes responses | Standard Error 2.7 |
| 5 mg Tadalafil (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 5: Overall Satisfaction with Experience | 41.2 percentage of yes responses | Standard Error 2.68 |
| Placebo (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 5: Overall Satisfaction with Experience | 10.6 percentage of yes responses | Standard Error 2.68 |
| Placebo (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 4: Satisfied with Hardness | 11.5 percentage of yes responses | Standard Error 2.71 |
| Placebo (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 1: Able to Achieve Erection | 1.8 percentage of yes responses | Standard Error 1.62 |
| Placebo (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 3: Successful Intercourse | 12.6 percentage of yes responses | Standard Error 2.51 |
| Placebo (Period III) | Change From Baseline to 12-Week in Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 1-5 | Question 2: Able to Insert | 6.9 percentage of yes responses | Standard Error 2.23 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3
Assessed the percentage of Yes responses to the SEP diary Question 3 Did your erection last long enough for you to have successful intercourse? from Week 12 (end of double-Blind treatment) to Week 16 (end of open-label treatment).
Time frame: 12 weeks and 16 weeks
Population: All participants who were entered the open-label treatment, received at least 1 dose of study drug during open-label treatment, had Week 12 and at least 1 SEP diary Question 3 measurement during open-label treatment, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3 | End of Week 12 | 68.3 percentage of yes responses | Standard Deviation 38.25 |
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3 | End of Week 16 | 75.0 percentage of yes responses | Standard Deviation 34.49 |
| 5 mg Tadalafil (Period III) | Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3 | End of Week 16 | 75.5 percentage of yes responses | Standard Deviation 34.89 |
| 5 mg Tadalafil (Period III) | Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3 | End of Week 12 | 69.0 percentage of yes responses | Standard Deviation 37.88 |
| Placebo (Period III) | Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3 | End of Week 12 | 43.1 percentage of yes responses | Standard Deviation 39.03 |
| Placebo (Period III) | Change From Week 12 to Week 16 Percentage of Yes Responses to Sexual Encounter Profile (SEP) Questions 3 | End of Week 16 | 80.0 percentage of yes responses | Standard Deviation 34.37 |
p-value: 0.002Paired t-test
p-value: 0.004Paired t-test
p-value: <0.001Paired t-test
Secondary
Percentage of Participants Having International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 From 12 to 16 Weeks
Self-reported erectile function over the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (low/no erectile function) to 5 (high erectile function) and Question 15 is scored 1 (very low confidence) to 5 (very high confidence), for a total score ranging from 1 to 30. Higher scores represent better erectile function. Data presented are the percentage of participants who return to normal erectile function (IIEF-EF domain score ≥26) at end of open-label extension treatment period (Period IV).
Time frame: 12 weeks through 16 weeks
Population: All participants who were entered the open-label treatment, received at least 1 dose of study drug during open-label treatment, had Week 12 and at least 1 IIEF-EF measurement during open-label treatment, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Percentage of Participants Having International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 From 12 to 16 Weeks | 54.5 percentage of participants |
| 5 mg Tadalafil (Period III) | Percentage of Participants Having International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 From 12 to 16 Weeks | 59.8 percentage of participants |
| Placebo (Period III) | Percentage of Participants Having International Index of Erectile Function - Erectile Function (IIEF-EF) Domain Score Greater Than or Equal to 26 From 12 to 16 Weeks | 62.8 percentage of participants |
Secondary
Treatment Satisfaction Scale (TSS) - Partner Satisfaction With Medication Score at Week 12 Endpoint
The TSS - partner satisfaction with medication measured participant's partner satisfaction with treatment based on a 13-item questionnaire. The overall score was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Satisfaction with medication was analyzed using analysis of covariance (ANOVA). The model included factors of study, treatment group, and pooled site within study.
Time frame: Week 12
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline partner's satisfaction with medication measurement, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Treatment Satisfaction Scale (TSS) - Partner Satisfaction With Medication Score at Week 12 Endpoint | 52.5 units on a scale | Standard Error 1.97 |
| 5 mg Tadalafil (Period III) | Treatment Satisfaction Scale (TSS) - Partner Satisfaction With Medication Score at Week 12 Endpoint | 55.7 units on a scale | Standard Error 1.96 |
| Placebo (Period III) | Treatment Satisfaction Scale (TSS) - Partner Satisfaction With Medication Score at Week 12 Endpoint | 27.5 units on a scale | Standard Error 1.96 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA
Secondary
Treatment Satisfaction Scale (TSS) - Patient Satisfaction With Medication Score at Week 12 Endpoint
The TSS - patient satisfaction with medication measured participant satisfaction with treatment based on a 13-item questionnaire. The overall score was converted to a 0-100 scale with higher numbers on the scale indicating greater satisfaction. Satisfaction with medication was analyzed using analysis of covariance (ANOVA). The model included factors of study, treatment group, and pooled site within study.
Time frame: Week 12
Population: All randomized participants who received at least 1 dose of study drug, had a baseline and at least 1 post-baseline participant's satisfaction with medication measurement, excluding those with IIEF-EF domain score ≥26 (normal) at baseline. Last observation carried forward (LOCF) principle was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 2.5 mg Titrated to 5 mg Tadalafil (Period III) | Treatment Satisfaction Scale (TSS) - Patient Satisfaction With Medication Score at Week 12 Endpoint | 53.7 units on a scale | Standard Error 1.98 |
| 5 mg Tadalafil (Period III) | Treatment Satisfaction Scale (TSS) - Patient Satisfaction With Medication Score at Week 12 Endpoint | 55.9 units on a scale | Standard Error 1.98 |
| Placebo (Period III) | Treatment Satisfaction Scale (TSS) - Patient Satisfaction With Medication Score at Week 12 Endpoint | 24.8 units on a scale | Standard Error 1.97 |
p-value: <0.001ANOVA
p-value: <0.001ANOVA