Trial Outcomes & Findings for A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy (NCT NCT00106392)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

131 participants

Primary outcome timeframe

18 months

Results posted on

2010-11-23

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	62	69
Overall Study Baseline Participants	59	65
Overall Study Full Analysis Set (FAS)	53	61
Overall Study COMPLETED	36	42
Overall Study NOT COMPLETED	26	27

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tacrolimus n=59 Participants 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.	Placebo n=65 Participants 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.	Total n=124 Participants Total of all reporting groups
Age Continuous	55.1 years STANDARD_DEVIATION 6.2 • n=5 Participants	54.1 years STANDARD_DEVIATION 6.2 • n=7 Participants	54.6 years STANDARD_DEVIATION 6.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	65 Participants n=7 Participants	124 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	55 Participants n=5 Participants	63 Participants n=7 Participants	118 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tacrolimus n=32 Participants 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.	Placebo n=38 Participants 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.
Erectile Function Domain Score Between Treated and Untreated Groups	18.0 Erectile Function Domain Score Interval 1.0 to 30.0	23.5 Erectile Function Domain Score Interval 4.0 to 30.0

SECONDARY outcome

Timeframe: 24 months

Population: The number of participants analyzed represents Full Analysis Set (FAS), which is defined as participants evaluated for Efficacy and Safety.

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.

Outcome measures

Outcome measures
Measure	Tacrolimus n=53 Participants 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.	Placebo n=61 Participants 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.
Percentage of Patients Achieving Normal Spontaneous Erectile Function as Measured by the Erectile Function (EF) Domain Score	45.3 Percentage of Participants	54.1 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tacrolimus n=24 Participants 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.	Placebo n=33 Participants 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.
Time Taken to Achieve Normalization of the Erectile Function (EF) Domain Score	104.5 Days Interval 28.0 to 753.0	180.0 Days Interval 29.0 to 730.0

SECONDARY outcome

Timeframe: 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.

Patients were identified as successful responders if they answered affirmatively in the Patient Sexual Encounter Diary regarding successful sexual intercourse after using impotence medication.

Outcome measures

Outcome measures
Measure	Tacrolimus n=52 Participants 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.	Placebo n=58 Participants 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.
Percentage of Patients Considered Successful Responders to Impotence Medications	73.1 Percentage of Participants	86.2 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tacrolimus n=38 Participants 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.	Placebo n=50 Participants 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.
Time to Achieve Response to Impotence Medications	102.0 Days Interval 34.0 to 730.0	113.5 Days Interval 29.0 to 821.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Tacrolimus n=39 Participants 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.	Placebo n=47 Participants 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.
Continence Level as Quantified by Part I of the Prostate Health-Related Quality of Life Questionnaire	22.0 Overall Score of Urinary Function Interval 16.0 to 49.0	22.0 Overall Score of Urinary Function Interval 16.0 to 52.0

Adverse Events

Tacrolimus

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tacrolimus n=59 participants at risk 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.	Placebo n=65 participants at risk 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	1.7% 1/59 • SAEs and AEs as defined below were collected through month 6. Serious Adverse Events possibly related to study drug were collected. The only other Adverse Events collected were those associated with study drug dose changes. Subjects who experienced an Adverse Event with the same preferred term multiple times were only counted once.	0.00% 0/65 • SAEs and AEs as defined below were collected through month 6. Serious Adverse Events possibly related to study drug were collected. The only other Adverse Events collected were those associated with study drug dose changes. Subjects who experienced an Adverse Event with the same preferred term multiple times were only counted once.

Other adverse events

Other adverse events
Measure	Tacrolimus n=59 participants at risk 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.	Placebo n=65 participants at risk 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.
Metabolism and nutrition disorders Hyperkalaemia	6.8% 4/59 • SAEs and AEs as defined below were collected through month 6. Serious Adverse Events possibly related to study drug were collected. The only other Adverse Events collected were those associated with study drug dose changes. Subjects who experienced an Adverse Event with the same preferred term multiple times were only counted once.	3.1% 2/65 • SAEs and AEs as defined below were collected through month 6. Serious Adverse Events possibly related to study drug were collected. The only other Adverse Events collected were those associated with study drug dose changes. Subjects who experienced an Adverse Event with the same preferred term multiple times were only counted once.
Renal and urinary disorders Renal disorder	5.1% 3/59 • SAEs and AEs as defined below were collected through month 6. Serious Adverse Events possibly related to study drug were collected. The only other Adverse Events collected were those associated with study drug dose changes. Subjects who experienced an Adverse Event with the same preferred term multiple times were only counted once.	4.6% 3/65 • SAEs and AEs as defined below were collected through month 6. Serious Adverse Events possibly related to study drug were collected. The only other Adverse Events collected were those associated with study drug dose changes. Subjects who experienced an Adverse Event with the same preferred term multiple times were only counted once.

Additional Information

Senior Medical Director, Medical Affairs

Astellas Pharma Global Development

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document.
Publication restrictions are in place

Restriction type: OTHER