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REACTT: A Study of Tadalafil After Radical Prostatectomy

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01026818
Collaborator
(none)
583
Enrollment
52
Locations
3
Arms
35
Duration (Months)
11.2
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study will include patients with localized prostate cancer who experience erectile dysfunction following bilateral nerve-sparing radical prostatectomy. Patients will be randomly assigned to three treatment arms: Tadalafil 5 mg once a day, Tadalafil 20 mg on demand (prior to anticipated sexual activity), and placebo. Patients will stay on therapy for 9 months and after withdrawal of medication for 6 weeks, patients will be evaluated for recovery of unassisted erectile function (without medication). An open-label extension for three months will evaluate the responsiveness of all patients to Tadalafil 5 mg once a day. Further objectives are to evaluate the treatment satisfaction of the respective therapies.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
583 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Effect on Unassisted Erectile Function of the Early Use of Tadalafil 5 mg Once a Day and Tadalafil 20 mg On Demand Treatment for 9 Months in Subjects Undergoing Bilateral Nerve-Sparing Radical Prostatectomy
Study Start Date :
Nov 1, 2009
Actual Primary Completion Date :
Oct 1, 2012
Actual Study Completion Date :
Oct 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tadalafil daily [5 milligrams (mg)]

After the treatment period and 6-week study Drug-Free Period, all participants can continue on study in an optional 5-mg tadalafil 3-month Open-Label Period.

Drug: Tadalafil
Administered by mouth for 9 months
Other Names:
  • Cialis
  • LY450190

    		•
    Experimental: Tadalafil on demand (20 mg)

    After the treatment period and 6-week study Drug-Free Period, all participants can continue on study in an optional 5-mg tadalafil 3-month Open-Label Period.

    Drug: Tadalafil
    Administered by mouth for 9 months
    Other Names:
  • Cialis
  • LY450190

    		•
    Placebo Comparator: Placebo

    After the treatment period and 6-week study Drug-Free Period, all participants can continue on study in an optional 5-mg tadalafil 3-month Open-Label Period.

    Drug: Placebo
    Administered by mouth, daily or on demand for 9 months

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With a Score of Greater Than or Equal to 22 in the Erectile Function (EF) Domain of the International Index of Erectile Function (IIEF) Questionnaire [Month 10.5]

      Self-reported erectile function during the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (no sexual activity for Question 1, no sexual stimulation for Question 2 and did not attempt intercourse for Questions 3-5) 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 with an IIEF-EF Total Score greater than or equal to (≥) 22.

    Secondary Outcome Measures

    1. Percentage of Participants With a Score of Greater Than or Equal to 22 in the International Index of Erectile Function- Erectile Function (IIEF-EF) Domain [Month 9 and Month 13.5]

      Self-reported erectile function during the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (no sexual activity for Question 1, no sexual stimulation for Question 2 and did not attempt intercourse for Questions 3-5) 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 with an IIEF-EF Total Score greater than or equal to (≥) 22.

    2. Change From Baseline to Endpoint in the International Index of Erectile Function- Erectile Function (IIEF-EF) Total Score [Randomization (Baseline), Months 9 and 10.5 and 13.5]

      Self-reported erectile function during the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (no sexual activity for Question 1, no sexual stimulation for Question 2 and did not attempt intercourse for Questions 3-5) 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. The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for baseline score, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).

    3. Change From Baseline to Endpoint in the International Index of Erectile Function (IIEF) Domains (Intercourse Satisfaction Domain, Orgasmic Function Domain, Sexual Desire Domain, Overall Satisfaction Domain) [Randomization (Baseline), Months 9 and 10.5 and 13.5]

      Self-reported overall satisfaction during past 4 weeks. Orgasmic function score is sum of Questions (Q)9 and 10 of IIEF. Scores range from 0 (no sexual stimulation or intercourse) to 5 (high orgasm) for each Q, total 0 to 10. Sexual desire score is sum of Q11 and 12 of IIEF. Scores range from 1 (low/no desire) to 5 (high desire) for each Q, total 2 to 10. Intercourse satisfaction score is sum of Q6, 7 and 8 of IIEF. Scores range from 0 (no attempts for Q6, did not attempt intercourse for Q7 and no intercourse for Q8) to 5 (high satisfaction) for each Q, total 0 to 15. Overall satisfaction score is sum of Q13 and 14 of IIEF. Scores range from 1 (low/no satisfaction) to 5 (high satisfaction) for each Q, total 2 to 10. Higher total scores for each domain indicate higher function. MMRM analysis was used to calculate LS mean and 95% CI. LS mean values are adjusted for baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).

    4. Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) Questionnaire Mean Score [Months 9 and 13.5]

      The EDITS questionnaire is a validated questionnaire consisting of 11 questions evaluating self-reported satisfaction with the erectile dysfunction (ED) treatment. Responses were based on the experiences during the previous 4 weeks. Each question is rated on a scale of 0 (extremely low treatment satisfaction) to 4 (extremely high treatment satisfaction). The EDITS mean score was obtained by adding each individual result for all questions, dividing by the number of questions answered. The mean scores range from 0 (extremely low treatment satisfaction) to 4 (extremely high satisfaction). The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% Confidence Interval (CI). LS mean values are adjusted for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).

    5. Change From Baseline in Self Esteem and Relationship (SEAR) Questionnaire Score [Randomization (Baseline), Months 9 and 13.5]

      The SEAR questionnaire is a participant-reported measure of psychosocial outcomes in men with erectile dysfunction (ED). It consists of 14 items. Sexual Relationship domain consists of 8 items (items 1-8). Items 2-8 are rated on a scale of 1 (Never) to 5 (Always), whereas item 1 is reverse scored (1=Always and 5=Never). The total scores for sexual relationship domain range from 8-40 with higher scores indicating better relationship. Self-Esteem subdomain contains items 9 through 12 rated on a scale of 1 (no/low self-esteem) to 5 (high self-esteem). Total scores for Self-Esteem subscale range from 4-20 with higher scores indicating higher self-esteem. The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% Confidence Interval (CI). LS mean values are adjusted for baseline domain score, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).

    6. Global Assessment Questions (GAQ) Question 1 at Month 9 [Month 9]

      GAQ Question 1: Choose the one number which best describes how you perceive your ability to achieve and maintain your erections now, compared to how it was before you began taking medication in this study. Responses range from very much better (1) to very much worse (7).

    7. Global Assessment Question (GAQ) Question 1 at Month 13.5 [Month 13.5]

      GAQ Question 1: Choose the one number which best describes how you perceive your ability to achieve and maintain your erections now, compared to how it was before you began taking medication in this study. Responses range from very much better (1) to very much worse (7).

    8. Global Assessment Question (GAQ) Question 2 at Month 9 [Month 9]

      GAQ Question 2: Choose the one number which best describes how you perceive your sexual life is now, compared to how it was before you began taking medication in this study. Responses range from very much better (1) to very much worse (7).

    9. Global Assessment Question (GAQ) Question 2 at Month 13.5 [Month 13.5]

      GAQ Question 2: Choose the one number which best describes how you perceive your sexual life is now, compared to how it was before you began taking medication in this study. Responses range from very much better (1) to very much worse (7).

    10. Residual Erectile Function (REF) at Baseline [Baseline]

      The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)

    11. Residual Erectile Function (REF) at Month 2 [Month 2]

      The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)

    12. Residual Erectile Function (REF) at Month 5 [Month 5]

      The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)

    13. Residual Erectile Function (REF) at Month 9 [Month 9]

      The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)

    14. Residual Erectile Function (REF) at Month 10.5 [Month 10.5]

      The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)

    15. Residual Erectile Function (REF) at Month 13.5 [Month 13.5]

      The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)

    16. Change From Baseline in 'Yes' Answers to Questions 1 to 5 of the Sexual Encounter Profile (SEP) [Randomization (Baseline), Months 9 and 10.5 and 13.5]

      Participant-assessed diary has 5 questions: Question (Q)1: erection achievement, Q2: successful penetration, Q3: successful intercourse, Q4: satisfied with erection, and Q5: satisfied with sexual experience) for each sexual encounter made over a specified period of time. SEP Q1-Q5 scores were determined as the percentage of 'Yes' responses to each of the 5 questions out of all sexual attempts recorded during the time period. The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).

    17. Change From Baseline in 'Yes' Answers to Morning Erections [Randomization (Baseline), Month 10.5]

      The participants were asked to complete the morning erections diary every morning during the 4-week period before randomization and during the 6-week, Drug-Free, Washout Period. Data presented are the changes in the participant's percentage of "yes" responses relative to the number of days the question was answered during treatment. The analysis of covariance (ANCOVA) was used to calculate Least Square (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for treatment, baseline morning erections frequency, age group and country.

    18. Standardized Morning Erections Question (SMEQ) Score at Month 2 [Month 2]

      Participants evaluated the frequency of their morning erections during the past 3-month period by answering the SMEQ ("Do you ever wake up with an erection") using a 4-point grading system ranging from 0 (Yes, regularly) to 3 (never).

    19. Standardized Morning Erections Question (SMEQ) Score at Month 9 [Month 9]

      Participants evaluated the frequency of their morning erections during the past 3-month period by answering the SMEQ ("Do you ever wake up with an erection") using a 4-point grading system ranging from 0 (Yes, regularly) to 3 (never).

    20. Standardized Morning Erections Question (SMEQ) Score at Month 13.5 [Month 13.5]

      Participants evaluated the frequency of their morning erections during the past 3-month period by answering the SMEQ ("Do you ever wake up with an erection") using a 4-point grading system ranging from 0 (Yes, regularly) to 3 (never).

    21. Change From Baseline in 26-item Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Score [Randomization (Baseline), Months 9 and 13.5]

      EPIC-26 (participants) contains 26 items and 5 domains: Urinary Incontinence (Items 1-4), Urinary Irritative/Obstructive (Items 5-8), Bowel (Items 10-15), Sexual (Items 16-21), and Hormonal (Items 22-26). Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0 to 100 scale for each domain, with higher scores representing better health-related quality of life. Responses are based on experiences during the previous 4 weeks. The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for baseline domain score, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).

    22. Change in Penile Length and Girth [Randomization (Baseline), Month 9]

      Measurements were performed with the penis in the flaccid state. The stretched penile length was measured from the tip of the glans to the pubopenile skin junction while applying tension to maximally stretch the penis. The penile circumference at midshaft was measured. All measurements were taken with a paper ruler to the nearest 0.5 centimeter (cm). The analysis of covariance (ANCOVA) was used to calculate Least Square (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for treatment, baseline, age group and country.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 67 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • scheduled to undergo Bilateral nerve-sparing radical prostatectomy (BNSRP) for organ-confined, non-metastatic prostate cancer

    • have a normal preoperative erectile function score of more or equal to 22 at screening(as evaluated by International Index of Erectile Function - Erectile Function domain (IIEF-EF))

    • develop Erectile Dysfunction (ED) (defined as the consistent inability to achieve and/or maintain an erection sufficient to permit satisfactory sexual intercourse) after surgery

    • have an interest in resuming sexual activity as soon as possible after surgery and anticipate having the same adult female sexual partner during the study

    • agree not to use any other treatment for ED, including herbal and over-the-counter (OTC) medications, during the study

    • does not require the initiation of adjuvant therapy for prostate cancer

    Exclusion Criteria:

    • history of ED

    • have received previous or current treatment with tadalafil or any other Phosphodiesterase Type 5 (PDE5) inhibitor

    • have undergone, or plan to undergo, radiation or hormonal therapy for prostate cancer

    • have a history of prostatic surgery or prostatic physical treatments

    • have a history of diabetes mellitus

    • have a history of galactose intolerance, lapp lactase deficiency, or glucose-galactose malabsorption

    • have clinically significant renal insufficiency as determined by the investigator

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Kortrijk Belgium 8500
    2 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Leuven Belgium 3000
    3 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Liège Belgium 4000
    4 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Calgary Alberta Canada T2W 1P9
    5 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Victoria British Columbia Canada V8T 5G1
    6 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. London Ontario Canada N6A 4V2
    7 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Creteil France 94010
    8 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Grenoble France 38043
    9 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lyon France 69437
    10 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Nice France 06002
    11 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Nimes France 30029
    12 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Pierre Benite France 69495
    13 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Berlin Germany 12203
    14 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Braunschweig Germany 38126
    15 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Dresden Germany 01307
    16 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Essen Germany 45122
    17 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Hamburg Germany 20246
    18 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Hannover Germany 30625
    19 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Herne Germany 44627
    20 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Leipzig Germany 04103
    21 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Leverkusen Germany 51375
    22 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Acquavivadellefonti Italy 70021
    23 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Bergamo Italy 24128
    24 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Bologna Italy 40138
    25 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Genova Italy 16132
    26 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Milano Italy 20132
    27 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Perugia Italy 06122
    28 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Amsterdam Netherlands 1066 CX
    29 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Leiden Netherlands 2300 RC
    30 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Nijmegen Netherlands 6532 SZ
    31 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Rotterdam Netherlands 3045 PM
    32 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. S-Hertogenbosch Netherlands 5211 NL
    33 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Veldhoven Netherlands 5504 DB
    34 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Bydgoszcz Poland 85-168
    35 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Gdansk Poland 80-952
    36 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Kielce Poland 25-734
    37 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Warsaw Poland 02-005
    38 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Zabrze Poland 41-800
    39 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Aravaca Spain 28023
    40 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Cordoba Spain 14004
    41 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Madrid Spain 28046
    42 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Majadahonda Spain 28222
    43 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Málaga Spain 29010
    44 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Sevilla Spain 41013
    45 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Valencia Spain 46010
    46 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Basel Switzerland CH-4031
    47 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Luzern Switzerland CH-6000
    48 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Zurich Switzerland CH-8091
    49 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Cambridge Cambridgeshire United Kingdom CB2 0QQ
    50 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Middlesbrough Cleveland United Kingdom TS4 3BW
    51 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Stevenage Herts United Kingdom SG4 7NH
    52 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Withington Manchester United Kingdom M20 9BX

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01026818
    Other Study ID Numbers:
    • 13086
    • H6D-EW-LVIK
    First Posted:
    Dec 4, 2009
    Last Update Posted:
    Jan 14, 2014
    Last Verified:
    Dec 1, 2013
    Keywords provided by Eli Lilly and Company
    Erectile Dysfunction
    Radical Prostatectomy
    Additional relevant MeSH terms:
    Erectile Dysfunction
    Tadalafil

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail The study consisted of a 6-week screening period including the time of bilateral nerve-sparing radical prostatectomy (BNSRP) surgery, a 9-month, randomized Double-Blind (DB), Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label (OL) Period.
    Arm/Group Title Screen - BNSRP Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description BNSRP surgery during Screening Period. Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Period Title: Screening Period
    STARTED 583 0 0 0
    COMPLETED 423 0 0 0
    NOT COMPLETED 160 0 0 0
    Period Title: Screening Period
    STARTED 0 139 143 141
    Received at Least 1 Dose of Study Drug 0 139 143 141
    COMPLETED 0 114 122 115
    NOT COMPLETED 0 25 21 26
    Period Title: Screening Period
    STARTED 0 114 122 115
    COMPLETED 0 105 117 108
    NOT COMPLETED 0 9 5 7
    Period Title: Screening Period
    STARTED 0 105 117 108
    COMPLETED 0 98 112 105
    NOT COMPLETED 0 7 5 3

    Baseline Characteristics

    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo Total
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Total of all reporting groups
    Overall Participants 139 143 141 423
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.6
    (5.07)
    57.5
    (5.91)
    57.6
    (5.69)
    57.9
    (5.58)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Male
    139
    100%
    143
    100%
    141
    100%
    423
    100%
    Race/Ethnicity, Customized (participants) [Number]
    White
    137
    98.6%
    141
    98.6%
    138
    97.9%
    416
    98.3%
    American Indian or Alaska Native
    0
    0%
    1
    0.7%
    0
    0%
    1
    0.2%
    Asian
    0
    0%
    0
    0%
    1
    0.7%
    1
    0.2%
    Black or African American
    2
    1.4%
    1
    0.7%
    2
    1.4%
    5
    1.2%
    Region of Enrollment (participants) [Number]
    France
    12
    8.6%
    13
    9.1%
    13
    9.2%
    38
    9%
    Canada
    13
    9.4%
    13
    9.1%
    12
    8.5%
    38
    9%
    Belgium
    7
    5%
    9
    6.3%
    8
    5.7%
    24
    5.7%
    Poland
    10
    7.2%
    9
    6.3%
    8
    5.7%
    27
    6.4%
    Spain
    38
    27.3%
    39
    27.3%
    39
    27.7%
    116
    27.4%
    Germany
    26
    18.7%
    25
    17.5%
    27
    19.1%
    78
    18.4%
    Netherlands
    0
    0%
    2
    1.4%
    1
    0.7%
    3
    0.7%
    United Kingdom
    7
    5%
    8
    5.6%
    8
    5.7%
    23
    5.4%
    Switzerland
    1
    0.7%
    1
    0.7%
    1
    0.7%
    3
    0.7%
    Italy
    25
    18%
    24
    16.8%
    24
    17%
    73
    17.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With a Score of Greater Than or Equal to 22 in the Erectile Function (EF) Domain of the International Index of Erectile Function (IIEF) Questionnaire
    Description Self-reported erectile function during the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (no sexual activity for Question 1, no sexual stimulation for Question 2 and did not attempt intercourse for Questions 3-5) 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 with an IIEF-EF Total Score greater than or equal to (≥) 22.
    Time Frame Month 10.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had IIEF-EF Total Scores measurement at Month 10.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Number [percentage of participants]
    20.9
    15%
    16.9
    11.8%
    19.1
    13.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments A sample size of 412 randomized participants provided 84% power to detect a 20% difference in the proportions for the 3 treatment groups. The sample size allowed for a 20% withdrawal during the study.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.675
    Comments The Type I error was controlled for multiplicity using a Bonferroni-Hommel procedure. First the largest p-value for the odds ratio to placebo was tested at the 5% level and in case of no rejection the second p-value was tested at the 2.5% level.
    Method Regression, Logistic
    Comments The logistic regression model included terms for treatment group, country, and age group.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.14
    Confidence Interval (2-Sided) 95%
    0.63 to 2.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments A sample size of 412 randomized participants provided 84% power to detect a 20% difference in the proportions for the 3 treatment groups. The sample size allowed for a 20% withdrawal during the study.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.704
    Comments The Type I error was controlled for multiplicity using a Bonferroni-Hommel procedure. First the largest p-value for the odds ratio to placebo was tested at the 5% level and in case of no rejection the second p-value was tested at the 2.5% level.
    Method Regression, Logistic
    Comments The logistic regression model included terms for treatment group, country, and age group.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 0.89
    Confidence Interval (2-Sided) 95%
    0.48 to 1.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants With a Score of Greater Than or Equal to 22 in the International Index of Erectile Function- Erectile Function (IIEF-EF) Domain
    Description Self-reported erectile function during the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (no sexual activity for Question 1, no sexual stimulation for Question 2 and did not attempt intercourse for Questions 3-5) 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 with an IIEF-EF Total Score greater than or equal to (≥) 22.
    Time Frame Month 9 and Month 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had IIEF-EF Total Scores measurements at Months 9 and 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Month 9
    25.2
    18.1%
    19.7
    13.8%
    14.2
    10.1%
    Month 13.5
    32.4
    23.3%
    33.1
    23.1%
    27.0
    19.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.016
    Comments P-value is for Month 9.
    Method Regression, Logistic
    Comments The logistic regression model included terms for treatment group, country, and age group.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.15
    Confidence Interval (2-Sided) 95%
    1.16 to 3.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.210
    Comments P-value is for Month 9.
    Method Regression, Logistic
    Comments The logistic regression model included terms for treatment group, country, and age group.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.50
    Confidence Interval (2-Sided) 95%
    0.79 to 2.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.273
    Comments P-value is for Month 13.5.
    Method Regression, Logistic
    Comments The logistic regression model included terms for treatment group, country, and age group.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.34
    Confidence Interval (2-Sided) 95%
    0.79 to 2.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.259
    Comments P-value is for Month 13.5.
    Method Regression, Logistic
    Comments The logistic regression model included terms for treatment group, country, and age group.
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 1.35
    Confidence Interval (2-Sided) 95%
    0.80 to 2.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline to Endpoint in the International Index of Erectile Function- Erectile Function (IIEF-EF) Total Score
    Description Self-reported erectile function during the past 4 weeks. IIEF- EF is the sum of Questions 1-5 and 15 of the IIEF. Questions 1-5 are scored 0 (no sexual activity for Question 1, no sexual stimulation for Question 2 and did not attempt intercourse for Questions 3-5) 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. The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for baseline score, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Time Frame Randomization (Baseline), Months 9 and 10.5 and 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug, had baseline and at least one post-baseline IIEF-EF Total Scores measurement at Months 9, 10.5 and 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Month 9
    7.73
    6.53
    4.93
    Month 10.5
    6.24
    5.76
    5.98
    Month 13.5
    10.60
    9.78
    8.97
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments P-value is for Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 2.80
    Confidence Interval (2-Sided) 95%
    0.76 to 4.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.03
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.118
    Comments P-value is for Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean differences
    Estimated Value 1.59
    Confidence Interval (2-Sided) 95%
    -0.41 to 3.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.02
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.802
    Comments P-value is for Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.26
    Confidence Interval (2-Sided) 95%
    -1.79 to 2.31
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.04
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.830
    Comments P-value is for Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.22
    Confidence Interval (2-Sided) 95%
    -2.23 to 1.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.02
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.184
    Comments P-value is for Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 1.62
    Confidence Interval (2-Sided) 95%
    -0.78 to 4.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.22
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.500
    Comments P-value is for Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.81
    Confidence Interval (2-Sided) 95%
    -1.54 to 3.16
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.20
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline to Endpoint in the International Index of Erectile Function (IIEF) Domains (Intercourse Satisfaction Domain, Orgasmic Function Domain, Sexual Desire Domain, Overall Satisfaction Domain)
    Description Self-reported overall satisfaction during past 4 weeks. Orgasmic function score is sum of Questions (Q)9 and 10 of IIEF. Scores range from 0 (no sexual stimulation or intercourse) to 5 (high orgasm) for each Q, total 0 to 10. Sexual desire score is sum of Q11 and 12 of IIEF. Scores range from 1 (low/no desire) to 5 (high desire) for each Q, total 2 to 10. Intercourse satisfaction score is sum of Q6, 7 and 8 of IIEF. Scores range from 0 (no attempts for Q6, did not attempt intercourse for Q7 and no intercourse for Q8) to 5 (high satisfaction) for each Q, total 0 to 15. Overall satisfaction score is sum of Q13 and 14 of IIEF. Scores range from 1 (low/no satisfaction) to 5 (high satisfaction) for each Q, total 2 to 10. Higher total scores for each domain indicate higher function. MMRM analysis was used to calculate LS mean and 95% CI. LS mean values are adjusted for baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Time Frame Randomization (Baseline), Months 9 and 10.5 and 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug, had baseline and at least one post-baseline IIEF domain scores measurements at Months 9, 10.5 and 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Orgasmic function - Month 9
    2.76
    2.48
    2.39
    Orgasmic function - Month 10.5
    2.94
    2.48
    2.48
    Orgasmic function - Month 13.5
    3.57
    2.90
    3.42
    Sexual desire - Month 9
    0.65
    0.65
    0.63
    Sexual desire - Month 10.5
    0.61
    0.65
    0.55
    Sexual desire - Month 13.5
    1.04
    0.89
    0.95
    Intercourse satisfaction - Month 9
    3.89
    3.50
    2.96
    Intercourse satisfaction - Month 10.5
    3.21
    2.81
    2.72
    Intercourse satisfaction - Month 13.5
    4.70
    4.08
    4.14
    Overall satisfaction - Month 9
    0.97
    0.93
    0.78
    Overall satisfaction - Month 10.5
    0.64
    0.48
    0.72
    Overall satisfaction - Month 13.5
    1.50
    1.57
    1.52
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.340
    Comments P-value is for orgasmic function - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.37
    Confidence Interval () 95%
    -0.39 to 1.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.39
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.821
    Comments P-value is for orgasmic function - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.09
    Confidence Interval (2-Sided) 95%
    -0.67 to 0.84
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.38
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.268
    Comments P-value is for orgasmic function - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.46
    Confidence Interval (2-Sided) 95%
    -0.36 to 1.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.42
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.998
    Comments P-value is for orgasmic function - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.00
    Confidence Interval (2-Sided) 95%
    -0.80 to 0.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.728
    Comments P-value is for orgasmic function - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.15
    Confidence Interval (2-Sided) 95%
    -0.68 to 0.97
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.42
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.203
    Comments P-value is for orgasmic function - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.52
    Confidence Interval (2-Sided) 95%
    -1.33 to 0.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.41
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.950
    Comments P-value is for sexual desire - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.02
    Confidence Interval (2-Sided) 95%
    -0.46 to 0.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.950
    Comments P-value is for sexual desire - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.01
    Confidence Interval (2-Sided) 95%
    -0.45 to 0.48
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.792
    Comments P-value is for sexual desire - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.06
    Confidence Interval (2-Sided) 95%
    -0.39 to 0.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.23
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.631
    Comments P-value is for sexual desire - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.11
    Confidence Interval (2-Sided) 95%
    -0.34 to 0.55
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.23
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.691
    Comments P-value is for sexual desire - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -0.38 to 0.58
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.801
    Comments P-value is for sexual desire - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.06
    Confidence Interval (2-Sided) 95%
    -0.53 to 0.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.24
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.065
    Comments P-value is for intercourse satisfaction - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.93
    Confidence Interval (2-Sided) 95%
    -0.06 to 1.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.50
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.274
    Comments P-value is for intercourse satisfaction - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.54
    Confidence Interval (2-Sided) 95%
    -0.43 to 1.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.49
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.359
    Comments P-value is for intercourse satisfaction - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.48
    Confidence Interval (2-Sided) 95%
    -0.55 to 1.52
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.53
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.863
    Comments P-value is for intercourse satisfaction - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.09
    Confidence Interval (2-Sided) 95%
    -0.93 to 1.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.52
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.314
    Comments P-value is for intercourse satisfaction - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.56
    Confidence Interval (2-Sided) 95%
    -0.53 to 1.66
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.56
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.910
    Comments P-value is for intercourse satisfaction - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.06
    Confidence Interval (2-Sided) 95%
    -1.13 to 1.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.54
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.532
    Comments P-value is for overall satisfaction - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.19
    Confidence Interval (2-Sided) 95%
    -0.40 to 0.78
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.30
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.620
    Comments P-value is for overall satisfaction - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.15
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.30
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.792
    Comments P-value is for overall satisfaction - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.08
    Confidence Interval (2-Sided) 95%
    -0.67 to 0.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.30
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.410
    Comments P-value is for overall satisfaction - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.24
    Confidence Interval (2-Sided) 95%
    -0.82 to 0.34
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.955
    Comments P-value is for overall satisfaction - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.02
    Confidence Interval () 95%
    -0.68 to 0.65
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.868
    Comments P-value is for overall satisfaction - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.05
    Confidence Interval (2-Sided) 95%
    -0.59 to 0.70
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments
    5. Secondary Outcome
    Title Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) Questionnaire Mean Score
    Description The EDITS questionnaire is a validated questionnaire consisting of 11 questions evaluating self-reported satisfaction with the erectile dysfunction (ED) treatment. Responses were based on the experiences during the previous 4 weeks. Each question is rated on a scale of 0 (extremely low treatment satisfaction) to 4 (extremely high treatment satisfaction). The EDITS mean score was obtained by adding each individual result for all questions, dividing by the number of questions answered. The mean scores range from 0 (extremely low treatment satisfaction) to 4 (extremely high satisfaction). The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% Confidence Interval (CI). LS mean values are adjusted for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Time Frame Months 9 and 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had EDITS mean scores measurements at Months 9 and 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Month 9
    2.21
    (0.11)
    2.11
    1.88
    Month 13.5
    2.54
    2.38
    2.25
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments P-value is for Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.33
    Confidence Interval (2-Sided) 95%
    0.10 to 0.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.12
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.041
    Comments P-value is for Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.23
    Confidence Interval (2-Sided) 95%
    0.01 to 0.45
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.11
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.035
    Comments P-value is for Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.28
    Confidence Interval () 95%
    0.02 to 0.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.316
    Comments P-value is for Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.13
    Confidence Interval (2-Sided) 95%
    -0.12 to 0.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.13
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in Self Esteem and Relationship (SEAR) Questionnaire Score
    Description The SEAR questionnaire is a participant-reported measure of psychosocial outcomes in men with erectile dysfunction (ED). It consists of 14 items. Sexual Relationship domain consists of 8 items (items 1-8). Items 2-8 are rated on a scale of 1 (Never) to 5 (Always), whereas item 1 is reverse scored (1=Always and 5=Never). The total scores for sexual relationship domain range from 8-40 with higher scores indicating better relationship. Self-Esteem subdomain contains items 9 through 12 rated on a scale of 1 (no/low self-esteem) to 5 (high self-esteem). Total scores for Self-Esteem subscale range from 4-20 with higher scores indicating higher self-esteem. The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% Confidence Interval (CI). LS mean values are adjusted for baseline domain score, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Time Frame Randomization (Baseline), Months 9 and 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post-baseline SEAR scores measurement at Months 9 and 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Sexual relationship - Month 9
    4.78
    3.50
    3.02
    Sexual relationship - Month 13.5
    6.90
    6.68
    6.72
    Self-esteem - Month 9
    0.78
    0.79
    0.51
    Self-esteem - Month 13.5
    1.67
    1.72
    1.62
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.086
    Comments P-value is for sexual relationship - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 1.75
    Confidence Interval (2-Sided) 95%
    -0.25 to 3.76
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.02
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.637
    Comments P-value is for sexual relationship - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.47
    Confidence Interval (2-Sided) 95%
    -1.50 to 2.45
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.00
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.885
    Comments P-value is for sexual relationship - Month 13.5
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.17
    Confidence Interval (2-Sided) 95%
    -2.18 to 2.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.20
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.972
    Comments P-value is for sexual relationship - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.04
    Confidence Interval (2-Sided) 95%
    -2.34 to 2.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.17
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.621
    Comments P-value is for self-esteem - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.27
    Confidence Interval (2-Sided) 95%
    -0.81 to 1.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.55
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.598
    Comments P-value is for self-esteem - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.29
    Confidence Interval (2-Sided) 95%
    -0.78 to 1.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.54
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.923
    Comments P-value is for self-esteem - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.06
    Confidence Interval (2-Sided) 95%
    -1.10 to 1.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.59
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.857
    Comments P-value is for self-esteem - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -1.03 to 1.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.58
    Estimation Comments
    7. Secondary Outcome
    Title Global Assessment Questions (GAQ) Question 1 at Month 9
    Description GAQ Question 1: Choose the one number which best describes how you perceive your ability to achieve and maintain your erections now, compared to how it was before you began taking medication in this study. Responses range from very much better (1) to very much worse (7).
    Time Frame Month 9

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had GAQ Q1 assessed at Month 9.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 114 122 115
    Very much better
    9
    6.5%
    10
    7%
    4
    2.8%
    Much better
    12
    8.6%
    22
    15.4%
    9
    6.4%
    A little better
    33
    23.7%
    32
    22.4%
    22
    15.6%
    No change
    31
    22.3%
    28
    19.6%
    48
    34%
    A little worse
    4
    2.9%
    5
    3.5%
    3
    2.1%
    Much worse
    6
    4.3%
    8
    5.6%
    6
    4.3%
    Very much worse
    8
    5.8%
    11
    7.7%
    14
    9.9%
    Missing
    11
    7.9%
    6
    4.2%
    9
    6.4%
    8. Secondary Outcome
    Title Global Assessment Question (GAQ) Question 1 at Month 13.5
    Description GAQ Question 1: Choose the one number which best describes how you perceive your ability to achieve and maintain your erections now, compared to how it was before you began taking medication in this study. Responses range from very much better (1) to very much worse (7).
    Time Frame Month 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had GAQ Q1 assessed at Month 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 100 114 106
    Very much better
    13
    9.4%
    19
    13.3%
    16
    11.3%
    Much better
    24
    17.3%
    25
    17.5%
    18
    12.8%
    A little Better
    28
    20.1%
    27
    18.9%
    28
    19.9%
    No Change
    19
    13.7%
    23
    16.1%
    26
    18.4%
    A little worse
    4
    2.9%
    4
    2.8%
    2
    1.4%
    Much worse
    3
    2.2%
    3
    2.1%
    5
    3.5%
    Very much worse
    5
    3.6%
    6
    4.2%
    6
    4.3%
    Missing
    4
    2.9%
    7
    4.9%
    5
    3.5%
    9. Secondary Outcome
    Title Global Assessment Question (GAQ) Question 2 at Month 9
    Description GAQ Question 2: Choose the one number which best describes how you perceive your sexual life is now, compared to how it was before you began taking medication in this study. Responses range from very much better (1) to very much worse (7).
    Time Frame Month 9

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had GAQ Q2 assessed at Month 9.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 114 122 115
    Very much better
    7
    5%
    7
    4.9%
    3
    2.1%
    Much better
    12
    8.6%
    25
    17.5%
    11
    7.8%
    A little better
    30
    21.6%
    26
    18.2%
    18
    12.8%
    No change
    31
    22.3%
    27
    18.9%
    49
    34.8%
    A little worse
    8
    5.8%
    10
    7%
    4
    2.8%
    Much worse
    7
    5%
    10
    7%
    10
    7.1%
    Very much worse
    9
    6.5%
    9
    6.3%
    11
    7.8%
    Missing
    10
    7.2%
    8
    5.6%
    9
    6.4%
    10. Secondary Outcome
    Title Global Assessment Question (GAQ) Question 2 at Month 13.5
    Description GAQ Question 2: Choose the one number which best describes how you perceive your sexual life is now, compared to how it was before you began taking medication in this study. Responses range from very much better (1) to very much worse (7).
    Time Frame Month 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had GAQ Q2 assessed at Month 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 100 114 106
    Very much better
    9
    6.5%
    20
    14%
    14
    9.9%
    Much better
    29
    20.9%
    23
    16.1%
    21
    14.9%
    A little better
    20
    14.4%
    26
    18.2%
    24
    17%
    No change
    25
    18%
    24
    16.8%
    26
    18.4%
    A little worse
    4
    2.9%
    5
    3.5%
    5
    3.5%
    Much worse
    4
    2.9%
    3
    2.1%
    7
    5%
    Very much worse
    5
    3.6%
    6
    4.2%
    4
    2.8%
    Missing
    4
    2.9%
    7
    4.9%
    5
    3.5%
    11. Secondary Outcome
    Title Residual Erectile Function (REF) at Baseline
    Description The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had REF assessed at baseline.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    REF = 0
    61
    43.9%
    62
    43.4%
    64
    45.4%
    REF = 1
    46
    33.1%
    48
    33.6%
    47
    33.3%
    REF = 2
    18
    12.9%
    17
    11.9%
    17
    12.1%
    REF = 3
    12
    8.6%
    11
    7.7%
    13
    9.2%
    REF = 4
    0
    0%
    2
    1.4%
    0
    0%
    Missing
    2
    1.4%
    2
    1.4%
    0
    0%
    12. Secondary Outcome
    Title Residual Erectile Function (REF) at Month 2
    Description The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)
    Time Frame Month 2

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had REF assessed at Month 2.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    REF = 0
    28
    20.1%
    27
    18.9%
    38
    27%
    REF = 1
    38
    27.3%
    51
    35.7%
    53
    37.6%
    REF = 2
    26
    18.7%
    28
    19.6%
    19
    13.5%
    REF = 3
    25
    18%
    23
    16.1%
    15
    10.6%
    REF = 4
    9
    6.5%
    5
    3.5%
    5
    3.5%
    Missing
    13
    9.4%
    8
    5.6%
    11
    7.8%
    13. Secondary Outcome
    Title Residual Erectile Function (REF) at Month 5
    Description The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)
    Time Frame Month 5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had REF assessed at Month 5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 123 128 123
    REF = 0
    12
    8.6%
    21
    14.7%
    27
    19.1%
    REF = 1
    37
    26.6%
    39
    27.3%
    35
    24.8%
    REF = 2
    19
    13.7%
    21
    14.7%
    27
    19.1%
    REF = 3
    32
    23%
    34
    23.8%
    19
    13.5%
    REF = 4
    15
    10.8%
    6
    4.2%
    6
    4.3%
    Missing
    8
    5.8%
    7
    4.9%
    9
    6.4%
    14. Secondary Outcome
    Title Residual Erectile Function (REF) at Month 9
    Description The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)
    Time Frame Month 9

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had REF assessed at Month 9.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 114 122 115
    REF = 0
    11
    7.9%
    17
    11.9%
    23
    16.3%
    REF = 1
    25
    18%
    28
    19.6%
    35
    24.8%
    REF = 2
    22
    15.8%
    30
    21%
    23
    16.3%
    REF = 3
    23
    16.5%
    27
    18.9%
    18
    12.8%
    REF = 4
    20
    14.4%
    15
    10.5%
    10
    7.1%
    Missing
    13
    9.4%
    5
    3.5%
    6
    4.3%
    15. Secondary Outcome
    Title Residual Erectile Function (REF) at Month 10.5
    Description The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)
    Time Frame Month 10.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had REF assessed at Month 10.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 105 117 108
    REF = 0
    13
    9.4%
    17
    11.9%
    22
    15.6%
    REF = 1
    29
    20.9%
    30
    21%
    29
    20.6%
    REF = 2
    25
    18%
    23
    16.1%
    19
    13.5%
    REF = 3
    22
    15.8%
    31
    21.7%
    22
    15.6%
    REF = 4
    12
    8.6%
    10
    7%
    14
    9.9%
    Missing
    4
    2.9%
    6
    4.2%
    2
    1.4%
    16. Secondary Outcome
    Title Residual Erectile Function (REF) at Month 13.5
    Description The participant is asked to rate the hardness of his erection using a 5-point grading system, with 0 (penis does not enlarge), 1 (penis is larger but not hard), 2 (penis is hard but not enough for penetration), 3 (penis is hard enough for penetration but not completely hard), 4 (penis is completely hard and fully rigid.)
    Time Frame Month 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had REF assessed at Month 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 100 114 106
    REF = 0
    5
    3.6%
    8
    5.6%
    11
    7.8%
    REF = 1
    19
    13.7%
    20
    14%
    25
    17.7%
    REF = 2
    17
    12.2%
    20
    14%
    15
    10.6%
    REF = 3
    34
    24.5%
    34
    23.8%
    28
    19.9%
    REF = 4
    21
    15.1%
    28
    19.6%
    24
    17%
    Missing
    4
    2.9%
    4
    2.8%
    3
    2.1%
    17. Secondary Outcome
    Title Change From Baseline in 'Yes' Answers to Questions 1 to 5 of the Sexual Encounter Profile (SEP)
    Description Participant-assessed diary has 5 questions: Question (Q)1: erection achievement, Q2: successful penetration, Q3: successful intercourse, Q4: satisfied with erection, and Q5: satisfied with sexual experience) for each sexual encounter made over a specified period of time. SEP Q1-Q5 scores were determined as the percentage of 'Yes' responses to each of the 5 questions out of all sexual attempts recorded during the time period. The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Time Frame Randomization (Baseline), Months 9 and 10.5 and 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post-baseline SEP questions answered at Months 9, 10.5 and 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Q1 - Month 9
    67.41
    63.88
    52.54
    Q1 - Month 10.5
    67.78
    64.24
    58.86
    Q1 - Month 13.5
    86.16
    79.79
    75.27
    Q2 - Month 9
    44.00
    34.29
    27.67
    Q2 - Month 10.5
    40.81
    34.99
    36.26
    Q2 - Month 13.5
    63.48
    56.07
    50.11
    Q3 - Month 9
    33.67
    24.09
    21.61
    Q3 - Month 10.5
    28.75
    23.01
    28.52
    Q3 - Month 13.5
    52.41
    45.83
    40.75
    Q4 - Month 9
    26.17
    18.15
    14.30
    Q4 - Month 10.5
    16.94
    11.74
    18.88
    Q4 - Month 13.5
    42.08
    35.62
    30.56
    Q5 - Month 9
    25.42
    17.73
    14.04
    Q5 - Month 10.5
    16.26
    10.52
    19.11
    Q5 - Month 13.5
    40.81
    34.96
    29.38
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments P-value is for Q1 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 14.87
    Confidence Interval (2-Sided) 95%
    3.92 to 25.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.57
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.038
    Comments P-value is for Q1 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 11.34
    Confidence Interval (2-Sided) 95%
    0.63 to 22.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.45
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.148
    Comments P-value is for Q1 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 8.91
    Confidence Interval (2-Sided) 95%
    -3.18 to 21.00
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.15
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.373
    Comments P-value is for Q1 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 5.37
    Confidence Interval (2-Sided) 95%
    -6.48 to 17.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.03
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.029
    Comments P-value is for Q1 - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 10.90
    Confidence Interval (2-Sided) 95%
    1.14 to 20.66
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.96
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.357
    Comments P-value is for Q1 - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 4.53
    Confidence Interval (2-Sided) 95%
    -5.12 to 14.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.91
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments P-value is for Q2 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 16.33
    Confidence Interval (2-Sided) 95%
    5.68 to 26.98
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.42
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.212
    Comments P-value is for Q2 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 6.62
    Confidence Interval (2-Sided) 95%
    -3.80 to 17.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.30
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.461
    Comments P-value is for Q2 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 4.55
    Confidence Interval (2-Sided) 95%
    -7.58 to 16.68
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.17
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.835
    Comments P-value is for Q2 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -1.26
    Confidence Interval (2-Sided) 95%
    -13.16 to 10.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.05
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.030
    Comments P-value is for Q2 - Month13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 13.36
    Confidence Interval (2-Sided) 95%
    1.27 to 25.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.15
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.326
    Comments P-value is for Q2 - Month13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 5.96
    Confidence Interval (2-Sided) 95%
    -5.97 to 17.89
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.07
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.019
    Comments P-value is for Q3 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 12.06
    Confidence Interval () 95%
    1.98 to 22.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.13
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.621
    Comments P-value is for Q3 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 2.48
    Confidence Interval (2-Sided) 95%
    -7.38 to 12.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.02
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.968
    Comments P-value is for Q3 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.23
    Confidence Interval () 95%
    -11.03 to 11.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.73
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.327
    Comments P-value is for Q3 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -5.51
    Confidence Interval (2-Sided) 95%
    -16.55 to 5.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.62
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.066
    Comments P-value is for Q3 - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 11.67
    Confidence Interval (2-Sided) 95%
    -0.76 to 24.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.32
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.415
    Comments P-value is for Q3 - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 5.09
    Confidence Interval (2-Sided) 95%
    -7.17 to 17.34
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.23
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments P-value is for Q4 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 11.87
    Confidence Interval (2-Sided) 95%
    2.79 to 20.94
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.61
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.394
    Comments P-value is for Q4 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 3.85
    Confidence Interval (2-Sided) 95%
    -5.03 to 12.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.51
    Estimation Comments
    Statistical Analysis 21
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.684
    Comments P-value is for Q4 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -1.94
    Confidence Interval (2-Sided) 95%
    -11.28 to 7.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.75
    Estimation Comments
    Statistical Analysis 22
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.126
    Comments P-value is for Q4 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -7.14
    Confidence Interval (2-Sided) 95%
    -16.30 to 2.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.66
    Estimation Comments
    Statistical Analysis 23
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.061
    Comments P-value is for Q4 - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 11.52
    Confidence Interval (2-Sided) 95%
    -0.53 to 23.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.13
    Estimation Comments
    Statistical Analysis 24
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.403
    Comments P-value is for Q4 - Month13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 5.06
    Confidence Interval (2-Sided) 95%
    -6.83 to 16.95
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.05
    Estimation Comments
    Statistical Analysis 25
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments P-value is for Q5 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 11.38
    Confidence Interval () 95%
    2.38 to 20.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.58
    Estimation Comments
    Statistical Analysis 26
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.410
    Comments P-value is for Q5 - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 3.69
    Confidence Interval (2-Sided) 95%
    -5.11 to 12.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.47
    Estimation Comments
    Statistical Analysis 27
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.537
    Comments P-value is for Q5 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -2.85
    Confidence Interval (2-Sided) 95%
    -11.92 to 6.22
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.61
    Estimation Comments
    Statistical Analysis 28
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.058
    Comments P-value is for Q5 - Month 10.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -8.59
    Confidence Interval (2-Sided) 95%
    -17.48 to 0.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.52
    Estimation Comments
    Statistical Analysis 29
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.061
    Comments P-value is for Q5 - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 11.44
    Confidence Interval (2-Sided) 95%
    -0.54 to 23.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.09
    Estimation Comments
    Statistical Analysis 30
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.353
    Comments P-value is for Q5 - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included terms for treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 5.59
    Confidence Interval (2-Sided) 95%
    -6.23 to 17.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.01
    Estimation Comments
    18. Secondary Outcome
    Title Change From Baseline in 'Yes' Answers to Morning Erections
    Description The participants were asked to complete the morning erections diary every morning during the 4-week period before randomization and during the 6-week, Drug-Free, Washout Period. Data presented are the changes in the participant's percentage of "yes" responses relative to the number of days the question was answered during treatment. The analysis of covariance (ANCOVA) was used to calculate Least Square (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for treatment, baseline morning erections frequency, age group and country.
    Time Frame Randomization (Baseline), Month 10.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had morning erection question answered at Baseline and Month 10.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Least Squares Mean (95% Confidence Interval) [percentage of "yes" response]
    8.92
    12.16
    14.04
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.162
    Comments
    Method ANCOVA
    Comments ANCOVA model included treatment, baseline, age group, and country.
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -5.12
    Confidence Interval (2-Sided) 95%
    -12.32 to 2.08
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.66
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.603
    Comments
    Method ANCOVA
    Comments ANCOVA model included treatment, baseline, age group, and country.
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -1.88
    Confidence Interval () 95%
    -8.99 to 5.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.61
    Estimation Comments
    19. Secondary Outcome
    Title Standardized Morning Erections Question (SMEQ) Score at Month 2
    Description Participants evaluated the frequency of their morning erections during the past 3-month period by answering the SMEQ ("Do you ever wake up with an erection") using a 4-point grading system ranging from 0 (Yes, regularly) to 3 (never).
    Time Frame Month 2

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had SMEQ measurement at Month 2
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Yes, regularly
    4
    2.9%
    7
    4.9%
    7
    5%
    Less frequently than in the past
    8
    5.8%
    15
    10.5%
    10
    7.1%
    Only occasionally
    41
    29.5%
    31
    21.7%
    26
    18.4%
    Never
    73
    52.5%
    80
    55.9%
    87
    61.7%
    Missing
    13
    9.4%
    9
    6.3%
    11
    7.8%
    20. Secondary Outcome
    Title Standardized Morning Erections Question (SMEQ) Score at Month 9
    Description Participants evaluated the frequency of their morning erections during the past 3-month period by answering the SMEQ ("Do you ever wake up with an erection") using a 4-point grading system ranging from 0 (Yes, regularly) to 3 (never).
    Time Frame Month 9

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had SMEQ measurement at Month 9.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 114 122 115
    Yes, regularly
    7
    5%
    9
    6.3%
    7
    5%
    Less frequently than in the past
    21
    15.1%
    19
    13.3%
    9
    6.4%
    Only occasionally
    36
    25.9%
    26
    18.2%
    27
    19.1%
    Never
    39
    28.1%
    61
    42.7%
    65
    46.1%
    Missing
    11
    7.9%
    7
    4.9%
    7
    5%
    21. Secondary Outcome
    Title Standardized Morning Erections Question (SMEQ) Score at Month 13.5
    Description Participants evaluated the frequency of their morning erections during the past 3-month period by answering the SMEQ ("Do you ever wake up with an erection") using a 4-point grading system ranging from 0 (Yes, regularly) to 3 (never).
    Time Frame Month 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had SMEQ measurement at Month 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 100 114 106
    Yes, regularly
    13
    9.4%
    15
    10.5%
    13
    9.2%
    Less frequently than in the past
    22
    15.8%
    24
    16.8%
    18
    12.8%
    Only occasionally
    31
    22.3%
    30
    21%
    27
    19.1%
    Never
    32
    23%
    40
    28%
    42
    29.8%
    Missing
    2
    1.4%
    5
    3.5%
    6
    4.3%
    22. Secondary Outcome
    Title Change From Baseline in 26-item Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire Score
    Description EPIC-26 (participants) contains 26 items and 5 domains: Urinary Incontinence (Items 1-4), Urinary Irritative/Obstructive (Items 5-8), Bowel (Items 10-15), Sexual (Items 16-21), and Hormonal (Items 22-26). Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0 to 100 scale for each domain, with higher scores representing better health-related quality of life. Responses are based on experiences during the previous 4 weeks. The Mixed Model for Repeated Measures (MMRM) analysis was used to calculate Least Squares (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for baseline domain score, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Time Frame Randomization (Baseline), Months 9 and 13.5

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug, had baseline and at least 1 post-baseline EPIC-26 scores measurement at Month 9 and Month 13.5.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Urinary Incontinence - Month 9
    34.08
    31.12
    30.59
    Urinary Incontinence - Month 13.5
    37.41
    35.54
    35.44
    Urinary Irritative/Obstructive - Month 9
    13.83
    13.28
    12.26
    Urinary Irritative/Obstructive - Month 13.5
    13.86
    13.82
    12.30
    Bowel - Month 9
    5.94
    6.27
    6.48
    Bowel - Month 13.5
    6.87
    6.49
    6.78
    Sexual - Month 9
    27.53
    20.66
    17.98
    Sexual - Month 13.5
    36.55
    32.58
    33.37
    Hormonal - Month 9
    1.72
    2.72
    -0.18
    Hormonal - Month 13.5
    2.48
    2.92
    3.01
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.196
    Comments P-value is for Urinary Incontinence - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 3.49
    Confidence Interval (2-Sided) 95%
    -1.82 to 8.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.70
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.841
    Comments P-value is for Urinary Incontinence - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.53
    Confidence Interval (2-Sided) 95%
    -4.69 to 5.75
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.65
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.474
    Comments P-value is for Urinary Incontinence - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 1.98
    Confidence Interval (2-Sided) 95%
    -3.45 to 7.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.76
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.971
    Comments P-value is for Urinary Incontinence - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -5.21 to 5.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.70
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.236
    Comments P-value is for Urinary Irritative/Obstructive - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 1.57
    Confidence Interval (2-Sided) 95%
    -1.03 to 4.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.32
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.429
    Comments P-value is for Urinary Irritative/Obstructive - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    -1.52 to 3.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.29
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.252
    Comments P-value is for Urinary Irritative/Obstructive - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 1.56
    Confidence Interval (2-Sided) 95%
    -1.12 to 4.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.36
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.251
    Comments P-value is for Urinary Irritative/Obstructive - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 1.52
    Confidence Interval (2-Sided) 95%
    -1.08 to 4.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.32
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.671
    Comments P-value is for Bowel - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.54
    Confidence Interval (2-Sided) 95%
    -3.03 to 1.95
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.27
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.868
    Comments P-value is for Bowel - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.21
    Confidence Interval (2-Sided) 95%
    -2.64 to 2.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.24
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.938
    Comments P-value is for Bowel - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -2.37 to 2.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.25
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.813
    Comments P-value is for Bowel - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -2.69 to 2.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.22
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments P-value is for Sexual - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 9.55
    Confidence Interval (2-Sided) 95%
    3.10 to 15.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.28
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.403
    Comments P-value is for Sexual - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 2.69
    Confidence Interval (2-Sided) 95%
    -3.63 to 9.00
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.21
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.406
    Comments P-value is for Sexual - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 3.18
    Confidence Interval (2-Sided) 95%
    -4.34 to 10.69
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.82
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.832
    Comments P-value is for Sexual - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.79
    Confidence Interval (2-Sided) 95%
    -8.11 to 6.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.72
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.197
    Comments P-value is for Hormonal - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 1.90
    Confidence Interval (2-Sided) 95%
    -0.99 to 4.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.47
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.045
    Comments P-value is for Hormonal - Month 9.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 2.89
    Confidence Interval (2-Sided) 95%
    0.06 to 5.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.44
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.692
    Comments P-value is for Hormonal - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.53
    Confidence Interval (2-Sided) 95%
    -3.16 to 2.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.34
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.943
    Comments P-value is for Hormonal - Month 13.5.
    Method Mixed Models Analysis
    Comments The MMRM model included baseline, treatment, country, visit, visit-by-treatment, age group, and age group-by-treatment (if significant at p<0.10).
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -0.09
    Confidence Interval (2-Sided) 95%
    -2.65 to 2.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.30
    Estimation Comments
    23. Secondary Outcome
    Title Change in Penile Length and Girth
    Description Measurements were performed with the penis in the flaccid state. The stretched penile length was measured from the tip of the glans to the pubopenile skin junction while applying tension to maximally stretch the penis. The penile circumference at midshaft was measured. All measurements were taken with a paper ruler to the nearest 0.5 centimeter (cm). The analysis of covariance (ANCOVA) was used to calculate Least Square (LS) mean and 95% confidence interval (CI). LS mean values are adjusted for treatment, baseline, age group and country.
    Time Frame Randomization (Baseline), Month 9

    Outcome Measure Data

    Analysis Population Description
    All randomized participants who received at least 1 dose of study drug and had penile measurements at Baseline and Month 9.
    Arm/Group Title Tadalafil 5 mg OaD Tadalafil 20 mg PRN Placebo
    Arm/Group Description Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-Week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    Measure Participants 139 142 141
    Length
    -1.53
    -7.26
    -5.73
    Girth
    0.03
    0.82
    -2.34
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.028
    Comments P-value is for length.
    Method ANCOVA
    Comments ANCOVA model included terms for treatment, baseline, age group and country.
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 4.20
    Confidence Interval (2-Sided) 95%
    0.47 to 7.93
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.89
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.413
    Comments P-value is for length.
    Method ANCOVA
    Comments ANCOVA model included terms for treatment, baseline, age group and country.
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value -1.53
    Confidence Interval (2-Sided) 95%
    -5.20 to 2.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.87
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tadalafil 5 mg OaD, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.112
    Comments P-value is for girth.
    Method ANCOVA
    Comments ANCOVA model included terms for treatment, baseline, age group and country.
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 2.37
    Confidence Interval (2-Sided) 95%
    -0.55 to 5.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.49
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tadalafil 20 mg PRN, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.031
    Comments P-value is for girth.
    Method ANCOVA
    Comments ANCOVA model included terms for treatment, baseline, age group and country.
    Method of Estimation Estimation Parameter LS Mean Differences
    Estimated Value 3.16
    Confidence Interval (2-Sided) 95%
    0.29 to 6.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.46
    Estimation Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Screen - BNSRP Tadalafil 5 mg OaD (Double-Blind Period/Washout Period) Tadalafil 20 mg PRN (Double-Blind Period/Washout Period) Placebo (Double-Blind Period/Washout Period) Tadalafil 5 mg OaD (Open-Label Period) Tadalfil 20 mg PRN (Open-Label Period) Placebo (Open-Label Period)
    Arm/Group Description Had bilateral nerve-sparing radical prostatectomy (BNSRP) surgery during Screening Period. Tadalafil 5 mg once a day (OaD) + Placebo as required/on demand (PRN) for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period. Tadalafil 5 mg OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Tadalafil 20 mg PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD. Placebo OaD + Placebo PRN for 9 months during Double-Blind, Placebo-Controlled Treatment Period, followed by a 6-week, Drug-Free Washout Period, and a 3-month, Open-Label Period with tadalafil 5 mg OaD.
    All Cause Mortality
    Screen - BNSRP Tadalafil 5 mg OaD (Double-Blind Period/Washout Period) Tadalafil 20 mg PRN (Double-Blind Period/Washout Period) Placebo (Double-Blind Period/Washout Period) Tadalafil 5 mg OaD (Open-Label Period) Tadalfil 20 mg PRN (Open-Label Period) Placebo (Open-Label Period)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Screen - BNSRP Tadalafil 5 mg OaD (Double-Blind Period/Washout Period) Tadalafil 20 mg PRN (Double-Blind Period/Washout Period) Placebo (Double-Blind Period/Washout Period) Tadalafil 5 mg OaD (Open-Label Period) Tadalfil 20 mg PRN (Open-Label Period) Placebo (Open-Label Period)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/583 (1%) 2/139 (1.4%) 3/143 (2.1%) 10/141 (7.1%) 1/139 (0.7%) 1/143 (0.7%) 2/141 (1.4%)
    Blood and lymphatic system disorders
    Splenomegaly 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Gastrointestinal disorders
    Constipation 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Rectal haemorrhage 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    General disorders
    Hernia obstructive 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pyrexia 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Immune system disorders
    Drug hypersensitivity 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Infections and infestations
    Abdominal abscess 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Erysipelas 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Sepsis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Urinary tract infection 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Injury, poisoning and procedural complications
    Intentional overdose 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Rotator cuff syndrome 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bronchial carcinoma 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Renal cancer 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Transitional cell carcinoma 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Nervous system disorders
    Ischaemic stroke 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Syncope 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Psychiatric disorders
    Depression 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Renal and urinary disorders
    Glomerulonephritis membranous 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Renal colic 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Renal impairment 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Urethral stenosis 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Urine flow decreased 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Reproductive system and breast disorders
    Pelvic haematoma 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Skin and subcutaneous tissue disorders
    Nail bed inflammation 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Vascular disorders
    Lymphocele 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Other (Not Including Serious) Adverse Events
    Screen - BNSRP Tadalafil 5 mg OaD (Double-Blind Period/Washout Period) Tadalafil 20 mg PRN (Double-Blind Period/Washout Period) Placebo (Double-Blind Period/Washout Period) Tadalafil 5 mg OaD (Open-Label Period) Tadalfil 20 mg PRN (Open-Label Period) Placebo (Open-Label Period)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 114/583 (19.6%) 50/139 (36%) 52/143 (36.4%) 40/141 (28.4%) 11/139 (7.9%) 18/143 (12.6%) 9/141 (6.4%)
    Blood and lymphatic system disorders
    Anaemia 5/583 (0.9%) 5 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Lymphadenopathy 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Cardiac disorders
    Bradycardia 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Palpitations 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Tachycardia 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Ear and labyrinth disorders
    Ear discomfort 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Tinnitus 0/583 (0%) 0 2/139 (1.4%) 2 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Endocrine disorders
    Androgen deficiency 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Autoimmune thyroiditis 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Hyperparathyroidism 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Hyperthyroidism 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Hypoprolactinaemia 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Eye disorders
    Blepharitis 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Chalazion 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Conjunctivitis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Diplopia 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Eye pain 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Eyelid pain 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Lacrimation increased 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Ocular discomfort 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Posterior capsule opacification 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Vision blurred 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 1/141 (0.7%) 1
    Gastrointestinal disorders
    Abdominal discomfort 0/583 (0%) 0 0/139 (0%) 0 2/143 (1.4%) 2 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Abdominal distension 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Abdominal pain lower 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Abdominal pain upper 4/583 (0.7%) 4 3/139 (2.2%) 3 2/143 (1.4%) 2 0/141 (0%) 0 0/139 (0%) 0 3/143 (2.1%) 3 0/141 (0%) 0
    Anal fistula 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Bowel movement irregularity 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Colitis 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Constipation 8/583 (1.4%) 8 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Diarrhoea 6/583 (1%) 6 1/139 (0.7%) 1 1/143 (0.7%) 2 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Dyspepsia 0/583 (0%) 0 5/139 (3.6%) 6 5/143 (3.5%) 5 1/141 (0.7%) 1 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0
    Flatulence 2/583 (0.3%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Frequent bowel movements 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Gastric haemorrhage 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Gastric ulcer 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Gastrointestinal pain 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Gastrooesophageal reflux disease 0/583 (0%) 0 1/139 (0.7%) 1 2/143 (1.4%) 2 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Haematochezia 0/583 (0%) 0 0/139 (0%) 0 2/143 (1.4%) 2 1/141 (0.7%) 1 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Haemorrhoids 2/583 (0.3%) 2 1/139 (0.7%) 1 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Hiatus hernia 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Inguinal hernia 0/583 (0%) 0 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Irritable bowel syndrome 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Nausea 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pancreatitis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Reflux gastritis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Tongue geographic 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Toothache 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Vomiting 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    General disorders
    Asthenia 3/583 (0.5%) 3 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Catheter site pain 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Chest pain 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Device occlusion 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Fatigue 3/583 (0.5%) 3 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Local swelling 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Oedema peripheral 0/583 (0%) 0 0/139 (0%) 0 2/143 (1.4%) 2 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pyrexia 1/583 (0.2%) 1 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Hepatobiliary disorders
    Hepatic function abnormal 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Immune system disorders
    Hypersensitivity 1/583 (0.2%) 1 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Seasonal allergy 0/583 (0%) 0 4/139 (2.9%) 4 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Infections and infestations
    Bronchitis 2/583 (0.3%) 2 3/139 (2.2%) 3 1/143 (0.7%) 1 2/141 (1.4%) 3 0/139 (0%) 0 0/143 (0%) 0 2/141 (1.4%) 2
    Catheter site infection 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Cystitis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Eye infection 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Gastroenteritis 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Haematoma infection 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Influenza 0/583 (0%) 0 0/139 (0%) 0 2/143 (1.4%) 2 1/141 (0.7%) 1 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Nail infection 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Nasopharyngitis 2/583 (0.3%) 2 5/139 (3.6%) 5 5/143 (3.5%) 5 3/141 (2.1%) 3 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Oral herpes 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Orchitis 2/583 (0.3%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pharyngitis 0/583 (0%) 0 0/139 (0%) 0 2/143 (1.4%) 2 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Post procedural infection 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Rhinitis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Sinusitis 0/583 (0%) 0 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Skin infection 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Staphylococcal infection 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Tonsillitis 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Tooth abscess 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Tooth infection 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Upper respiratory tract infection 0/583 (0%) 0 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Urethritis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Urinary tract infection 21/583 (3.6%) 23 3/139 (2.2%) 4 4/143 (2.8%) 4 2/141 (1.4%) 2 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Wound infection 2/583 (0.3%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Injury, poisoning and procedural complications
    Accidental overdose 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Anastomotic complication 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Arthropod bite 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Contusion 7/583 (1.2%) 10 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Haematuria traumatic 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Head injury 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Heat stroke 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Incision site blister 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Incision site complication 1/583 (0.2%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Incision site pain 6/583 (1%) 6 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Joint injury 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Ligament sprain 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Open wound 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Optic nerve injury 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Overdose 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Post procedural haematoma 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Post procedural haemorrhage 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Procedural pain 13/583 (2.2%) 14 0/139 (0%) 0 1/143 (0.7%) 1 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Skeletal injury 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Testicular injury 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Wound complication 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Investigations
    Arthroscopy 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Blood cholesterol increased 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Blood luteinising hormone decreased 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Blood pressure increased 0/583 (0%) 0 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Blood selenium decreased 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Blood selenium increased 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Blood testosterone decreased 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Blood thyroid stimulating hormone decreased 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Blood uric acid increased 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Oestradiol increased 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Urine output increased 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Weight decreased 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Weight increased 2/583 (0.3%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Metabolism and nutrition disorders
    Glucose tolerance impaired 0/583 (0%) 0 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Gout 2/583 (0.3%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Hypercholesterolaemia 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Obesity 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Vitamin d deficiency 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/583 (0.3%) 2 1/139 (0.7%) 1 2/143 (1.4%) 2 2/141 (1.4%) 2 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Back pain 1/583 (0.2%) 1 5/139 (3.6%) 5 5/143 (3.5%) 5 3/141 (2.1%) 3 0/139 (0%) 0 1/143 (0.7%) 1 1/141 (0.7%) 1
    Bone lesion 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Chondropathy 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Exostosis 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Foot deformity 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Groin pain 1/583 (0.2%) 1 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Intervertebral disc protrusion 0/583 (0%) 0 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Joint swelling 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Muscle spasms 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Muscular weakness 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Musculoskeletal chest pain 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Musculoskeletal pain 2/583 (0.3%) 2 0/139 (0%) 0 1/143 (0.7%) 1 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Myalgia 5/583 (0.9%) 5 5/139 (3.6%) 7 5/143 (3.5%) 7 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Neck pain 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Osteoarthritis 0/583 (0%) 0 1/139 (0.7%) 1 2/143 (1.4%) 2 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pain in extremity 2/583 (0.3%) 2 3/139 (2.2%) 3 4/143 (2.8%) 4 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Polyarthritis 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Rotator cuff syndrome 1/583 (0.2%) 1 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Spondylolisthesis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Synovial cyst 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Tendon pain 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Tendonitis 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lymphoma 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Renal cell carcinoma 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Nervous system disorders
    Carotid artery stenosis 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Convulsion 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Dizziness 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Essential tremor 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Facial paresis 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Headache 9/583 (1.5%) 10 5/139 (3.6%) 11 11/143 (7.7%) 16 6/141 (4.3%) 7 1/139 (0.7%) 2 2/143 (1.4%) 2 1/141 (0.7%) 1
    Hypoaesthesia 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Memory impairment 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Migraine 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Monoparesis 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Nerve compression 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Paraesthesia 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Somnolence 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Psychiatric disorders
    Anxiety 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 3/141 (2.1%) 3 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Depressed mood 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Depression 0/583 (0%) 0 2/139 (1.4%) 2 2/143 (1.4%) 2 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Insomnia 1/583 (0.2%) 1 0/139 (0%) 0 1/143 (0.7%) 1 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Libido decreased 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Mood altered 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Orgasm abnormal 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Renal and urinary disorders
    Bladder irritation 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Bladder tamponade 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Calculus urinary 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Haematuria 3/583 (0.5%) 3 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Hypertonic bladder 3/583 (0.5%) 3 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Incontinence 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Nephrolithiasis 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pollakiuria 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Renal colic 1/583 (0.2%) 1 1/139 (0.7%) 1 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Renal pain 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Stress urinary incontinence 5/583 (0.9%) 5 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Ureteric stenosis 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 2 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Urge incontinence 2/583 (0.3%) 2 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Urinary incontinence 34/583 (5.8%) 34 3/139 (2.2%) 3 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Urinary retention 3/583 (0.5%) 3 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Reproductive system and breast disorders
    Epididymitis 2/583 (0.3%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Genital discomfort 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Gynaecomastia 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pelvic discomfort 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pelvic haematoma 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pelvic pain 2/583 (0.3%) 2 1/139 (0.7%) 2 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Penile curvature 0/583 (0%) 0 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Perineal pain 4/583 (0.7%) 4 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pruritus genital 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Testicular pain 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 2/141 (1.4%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Epistaxis 0/583 (0%) 0 0/139 (0%) 0 2/143 (1.4%) 2 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Nasal congestion 2/583 (0.3%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Nasal inflammation 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Oropharyngeal pain 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Sinus congestion 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Throat irritation 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Dermatitis contact 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Eczema 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Hyperhidrosis 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Night sweats 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Pruritus 1/583 (0.2%) 1 1/139 (0.7%) 3 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Rash 0/583 (0%) 0 2/139 (1.4%) 2 2/143 (1.4%) 2 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Rash generalised 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Rosacea 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Scar pain 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Skin reaction 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Solar lentigo 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Surgical and medical procedures
    Arthroscopic surgery 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Bladder catheterisation 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Cataract operation 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 2 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Circumcision 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Dental implantation 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Eyelid operation 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Inguinal hernia repair 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Knee operation 0/583 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Lipoma excision 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Nephrectomy 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Polypectomy 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Tooth extraction 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Wart excision 0/583 (0%) 0 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Vascular disorders
    Deep vein thrombosis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Flushing 2/583 (0.3%) 2 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0
    Hot flush 1/583 (0.2%) 1 1/139 (0.7%) 1 1/143 (0.7%) 1 1/141 (0.7%) 1 0/139 (0%) 0 1/143 (0.7%) 1 0/141 (0%) 0
    Hypertension 2/583 (0.3%) 2 1/139 (0.7%) 1 2/143 (1.4%) 2 1/141 (0.7%) 1 1/139 (0.7%) 1 1/143 (0.7%) 1 0/141 (0%) 0
    Hypotension 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 1/139 (0.7%) 1 0/143 (0%) 0 0/141 (0%) 0
    Lymphocele 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1
    Lymphoedema 0/583 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 1/141 (0.7%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0
    Thrombosis 1/583 (0.2%) 1 0/139 (0%) 0 0/143 (0%) 0 0/141 (0%) 0 0/139 (0%) 0 0/143 (0%) 0 0/141 (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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01026818
    Other Study ID Numbers:
    • 13086
    • H6D-EW-LVIK
    First Posted:
    Dec 4, 2009
    Last Update Posted:
    Jan 14, 2014
    Last Verified:
    Dec 1, 2013