Erectile Dysfunction, Prostate Cancer
Conditions
Keywords
Treatment effectiveness, Treatment efficacy, Investigational, Therapies, Immunosuppressant, Erectile dysfunction, Prostatectomy
Brief summary
The purpose of the study is to compare the safety and effectiveness of Prograf in the prevention of erectile dysfunction in men after a radical prostatectomy.
Detailed description
The purpose of the study is to compare the safety and efficacy of Prograf versus placebo in the prevention of erectile dysfunction in men after a bilateral nerve-sparing radical prostatectomy.
Interventions
DRUGTacrolimus
oral
DRUGPlacebo
oral
Sponsors
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
No minimum to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male scheduled to undergo bilateral nerve sparing radical prostatectomy for prostate cancer.
Exclusion criteria
* Patient is \> 65 years of age * Patient has been diagnosed with Type 1 or Type 2 diabetes * Patient is actively smoking on a daily basis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Erectile Function Domain Score Between Treated and Untreated Groups | 18 months | Erectile function was assessed using the International Index of Erectile Function (IIEF) questionnaire, which consists of 15 questions. The erectile function domain score is calculated as a sum of scores from questions 1-5 and 15. A clinically meaningful difference is 5 points. The scores range from 1 to 30 points where a higher score indicates better erectile function. Normal erectile function is defined as greater than or equal to 24 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Achieving Normal Spontaneous Erectile Function as Measured by the Erectile Function (EF) Domain Score | 24 months | Erectile function was assessed using the International Index of Erectile Function (IIEF) questionnaire, which consists of 15 questions. The erectile function domain score is calculated as a sum of scores from questions 1-5 and 15. A clinically meaningful difference is 5 points. The scores range from 1 to 30 points where a higher score indicates better erectile function. Normal erectile function is defined as greater than or equal to 24 points. Percentages represent the proportions of participants who achieved normal erectile function at any time during the 24 months. |
| Time Taken to Achieve Normalization of the Erectile Function (EF) Domain Score | 24 months | Erectile function was assessed using the International Index of Erectile Function (IIEF) questionnaire, which consists of 15 questions. The EF domain score is calculated as a sum of scores from questions 1-5 and 15. A clinically meaningful difference is 5 points. Scores range from 1-30 points where a higher score indicates better erectile function. Normal erectile function is defined as greater than or equal to 24 points.Time to achieve normalization of the EF domain score was calculated based on the date of the assessment during which the EF domain score was first greater than or equal to 24. |
| Percentage of Patients Considered Successful Responders to Impotence Medications | 24 months | Patients were identified as successful responders if they answered affirmatively in the Patient Sexual Encounter Diary regarding successful sexual intercourse after using impotence medication. |
| Time to Achieve Response to Impotence Medications | 24 months | Time to achieve response to impotence medication was calculated based on the date of the assessment during which the first successful response was recorded. The specific date of the actual response is not reflected; only that it occurred since the previous study visit. |
| Continence Level as Quantified by Part I of the Prostate Health-Related Quality of Life Questionnaire | 24 months | Part 1 Urinary Function- Prostate Health-Related Quality-of-Life (QOL) Questionnaire consists of 16 questions asking patients about their continence and urinary habits over the previous four weeks. The responses to all 16 of these questions were added together to calculate an overall score for urinary function. The minimum possible score is 16 and the maximum possible score is 79. A higher score indicates a lower continence level. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tacrolimus Preoperatively: Tacrolimus 2 mg oral daily from 4 to 10 days prior to surgery through hospital discharge; Postoperatively: Tacrolimus 3 mg oral daily at time of hospital discharge through 6 months of follow up. | 59 |
| Placebo Preoperatively: Matching placebo oral daily from 4 to 10 days prior to surgery through hospital discharge; Postoperatively: Matching placebo oral daily at time of hospital discharge through 6 months of follow up. | 65 |
| Total | 124 |
Baseline characteristics
| Characteristic | Tacrolimus | Placebo | Total |
|---|---|---|---|
| Age Continuous | 55.1 years STANDARD_DEVIATION 6.2 | 54.1 years STANDARD_DEVIATION 6.2 | 54.6 years STANDARD_DEVIATION 6.2 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 55 Participants | 63 Participants | 118 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 59 Participants | 65 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 59 | 5 / 65 |
| serious Total, serious adverse events | 1 / 59 | 0 / 65 |
Outcome results
Primary
Erectile Function Domain Score Between Treated and Untreated Groups
Erectile function was assessed using the International Index of Erectile Function (IIEF) questionnaire, which consists of 15 questions. The erectile function domain score is calculated as a sum of scores from questions 1-5 and 15. A clinically meaningful difference is 5 points. The scores range from 1 to 30 points where a higher score indicates better erectile function. Normal erectile function is defined as greater than or equal to 24 points.
Time frame: 18 months
Population: The number of participants analyzed represents Full Analysis Set (FAS), which is defined as participants evaluated for Efficacy and Safety.~Only participants with complete IIEF questionnaire data at 18 months are included in the calculation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tacrolimus | Erectile Function Domain Score Between Treated and Untreated Groups | 18.0 Erectile Function Domain Score |
| Placebo | Erectile Function Domain Score Between Treated and Untreated Groups | 23.5 Erectile Function Domain Score |
Comparison: A group sequential design using the O'Brien and Fleming stopping rule will require 58 evaluable patients per group to detect a 5-point difference in the Erectile Function domain of the IIEF with a power of 80% and an overall significance level of 5%.p-value: 0.111Wilcoxon (Mann-Whitney)
Secondary
Continence Level as Quantified by Part I of the Prostate Health-Related Quality of Life Questionnaire
Part 1 Urinary Function- Prostate Health-Related Quality-of-Life (QOL) Questionnaire consists of 16 questions asking patients about their continence and urinary habits over the previous four weeks. The responses to all 16 of these questions were added together to calculate an overall score for urinary function. The minimum possible score is 16 and the maximum possible score is 79. A higher score indicates a lower continence level.
Time frame: 24 months
Population: The number of participants analyzed represents Full Analysis Set (FAS), which is defined as participants evaluated for Efficacy and Safety.~Only participants with a Prostate Health-Related QOL questionnaire at 24 months were included in the calculation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tacrolimus | Continence Level as Quantified by Part I of the Prostate Health-Related Quality of Life Questionnaire | 22.0 Overall Score of Urinary Function |
| Placebo | Continence Level as Quantified by Part I of the Prostate Health-Related Quality of Life Questionnaire | 22.0 Overall Score of Urinary Function |
p-value: 0.879Wilcoxon (Mann-Whitney)
Secondary
Percentage of Patients Achieving Normal Spontaneous Erectile Function as Measured by the Erectile Function (EF) Domain Score
Erectile function was assessed using the International Index of Erectile Function (IIEF) questionnaire, which consists of 15 questions. The erectile function domain score is calculated as a sum of scores from questions 1-5 and 15. A clinically meaningful difference is 5 points. The scores range from 1 to 30 points where a higher score indicates better erectile function. Normal erectile function is defined as greater than or equal to 24 points. Percentages represent the proportions of participants who achieved normal erectile function at any time during the 24 months.
Time frame: 24 months
Population: The number of participants analyzed represents Full Analysis Set (FAS), which is defined as participants evaluated for Efficacy and Safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus | Percentage of Patients Achieving Normal Spontaneous Erectile Function as Measured by the Erectile Function (EF) Domain Score | 45.3 Percentage of Participants |
| Placebo | Percentage of Patients Achieving Normal Spontaneous Erectile Function as Measured by the Erectile Function (EF) Domain Score | 54.1 Percentage of Participants |
p-value: 0.453Fisher Exact
Secondary
Percentage of Patients Considered Successful Responders to Impotence Medications
Patients were identified as successful responders if they answered affirmatively in the Patient Sexual Encounter Diary regarding successful sexual intercourse after using impotence medication.
Time frame: 24 months
Population: The number of participants analyzed represents Full Analysis Set (FAS), which is defined as participants evaluated for Efficacy and Safety.~Only participants who used any impotence medications were included in the calculation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus | Percentage of Patients Considered Successful Responders to Impotence Medications | 73.1 Percentage of Participants |
| Placebo | Percentage of Patients Considered Successful Responders to Impotence Medications | 86.2 Percentage of Participants |
p-value: 0.099Fisher Exact
Secondary
Time Taken to Achieve Normalization of the Erectile Function (EF) Domain Score
Erectile function was assessed using the International Index of Erectile Function (IIEF) questionnaire, which consists of 15 questions. The EF domain score is calculated as a sum of scores from questions 1-5 and 15. A clinically meaningful difference is 5 points. Scores range from 1-30 points where a higher score indicates better erectile function. Normal erectile function is defined as greater than or equal to 24 points.Time to achieve normalization of the EF domain score was calculated based on the date of the assessment during which the EF domain score was first greater than or equal to 24.
Time frame: 24 months
Population: The number of participants analyzed represents Full Analysis Set (FAS), which is defined as participants evaluated for Efficacy and Safety.~Only participants who achieved normal erectile function are included in the calculation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tacrolimus | Time Taken to Achieve Normalization of the Erectile Function (EF) Domain Score | 104.5 Days |
| Placebo | Time Taken to Achieve Normalization of the Erectile Function (EF) Domain Score | 180.0 Days |
p-value: 0.79Wilcoxon (Mann-Whitney)
Secondary
Time to Achieve Response to Impotence Medications
Time to achieve response to impotence medication was calculated based on the date of the assessment during which the first successful response was recorded. The specific date of the actual response is not reflected; only that it occurred since the previous study visit.
Time frame: 24 months
Population: The number of participants analyzed represents Full Analysis Set (FAS), which is defined as participants evaluated for Efficacy and Safety.~Only participants who had a successful response to impotence medications were included in the calculations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tacrolimus | Time to Achieve Response to Impotence Medications | 102.0 Days |
| Placebo | Time to Achieve Response to Impotence Medications | 113.5 Days |
p-value: 0.575Wilcoxon (Mann-Whitney)