A Study in Patients With Erectile Dysfunction

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01122264
• Collaborator: (none)
• Enrollment: 770
• Locations: 45
• Arms: 3
• Duration (Months): 13
• Patients Per Site: 17.1
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate if treatment in erectile dysfunction with a long-acting drug (Tadalafil) taken once a day or taken as needed results in a longer treatment adherence and better long term outcomes (over 24 weeks), compared with a short-acting drug (Sildenafil Citrate) taken as needed.

Condition or Disease	Intervention/Treatment	Phase
Erectile Dysfunction	Drug: Tadalafil; Drug: Sildenafil Citrate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 770 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Impact of Tadalafil (LY450190) Once a Day or Tadalafil on Demand Compared to Sildenafil Citrate on Demand on Treatment Discontinuation in Patients With Erectile Dysfunction Who Are naïve to PDE5 Inhibitors
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tadalafil on demand 10 milligrams (mg) or 20 mg on demand	Drug: Tadalafil; Administered orally for 24 weeks.; Other Names: Cialis LY450190
Experimental: Tadalafil once a day 5 mg or 2.5 mg once a day	Drug: Tadalafil; Administered orally for 24 weeks.; Other Names: Cialis LY450190
Active Comparator: Sildenafil Citrate 50 mg, 100 mg, or 25 mg on demand	Drug: Sildenafil Citrate; Administered orally for 24 weeks.

Outcome Measures

Primary Outcome Measures

1. Time to Discontinuation of Randomized Treatment [Baseline up to 334 days]

   Time to discontinuation of randomized treatment was defined as the number of days from randomization until the day the participant discontinued the randomized treatment. Discontinuation of randomized treatment was defined as switching between the 3 study treatments (tadalafil on demand, tadalafil once a day, or sildenafil citrate on demand) or discontinuing from all treatments. A change of dose within the same treatment was not considered switching of treatment. This outcome measure was estimated using the Kaplan-Meier product-limit method.

Secondary Outcome Measures

1. Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Erectile Function (EF) Domain [Baseline, 4, 8, 16, and 24 weeks]

   Self-reported EF score over past 4 weeks. Items 1-5 scores range from 0 (no sexual activity) to 5 (high EF). Item 15 score ranges from 1 (very low confidence to get/keep erection) to 5 (very high confidence). Total scores range from 1 to 30; lower scores denote greater erectile dysfunction severity. Least Squares Mean changes from baseline to endpoint for each visit from repeated measures analysis included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. Correlation matrix for repeated observations assumed to be unstructured.

2. Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Orgasmic Function Domain [Baseline, 4, 8, 16, and 24 weeks]

   Self-reported orgasmic function on the IIEF over past 4 weeks and consists of 2 questions (items 9 and 10). Each question is rated on a scale from 0 (no sexual stimulation) to 5 (almost always/always). Total scores range from 0 to 10; lower scores represent lower orgasmic function. Least Squares Mean changes from baseline to endpoint for each visit were from a repeated measures analysis and included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. The correlation matrix for the repeated observations was assumed to be unstructured.

3. Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Sexual Desire Domain [Baseline, 4, 8, 16, and 24 weeks]

   Self-reported sexual desire on IIEF over past 4 weeks; comprises 2 questions (items 11 and 12). Each question rated on a scale from 1 (almost never or low/no sexual desire) to 5 (almost always or very high sexual desire). Total scores range: 2 to 10; lower numerical scores denote lower sexual desire. Least Squares Mean changes from baseline to endpoint for each visit from repeated measures analysis and included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. Correlation matrix for repeated observations assumed to be unstructured.

4. Change From Baseline to 4, 8, 16 and 24 Weeks of the Sexual Encounter Profile (SEP) [Baseline, 4, 8, 16, and 24 weeks]

   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 specified period of time. SEP Q1-Q5 scores determined as percentage of 'Yes' responses to each of 5 questions out of all sexual attempts recorded during the time period. Least Squares Mean changes from baseline to endpoint for each visit from a repeated measures analysis included terms for baseline score, treatment group, country, visit, and visit*treatment.

5. Global Assessment Questions (GAQ) [24 weeks]

   The GAQ consists of 2 Yes/No/No Response (No Respo) questions. GAQ Question (Q)1: Has the treatment you have been taking during this study improved your erections? GAQ Q2: Has the treatment improved your ability to engage in sexual activity?

6. Number of Treatment Switches [Baseline through 24 weeks]

   The number of times participants switched erectile dysfunction medication within the 3 treatments being studied (tadalafil on demand, tadalafil once a day, or sildenafil citrate on demand).

7. Patterns of Erectile Dysfunction Treatment Change [Baseline through 24 weeks]

   Results are reported as the number of participants per sequence of study medications (tadalafil on demand, tadalafil once a day, or sildenafil citrate on demand) that were taken as a result of switching treatments. The Other Treatment Sequence reports the number of participants per sequence of study medications that were taken as a result of switching treatments more than once. The number of participants who did not switch is also reported.

8. Reasons for Discontinuation of Randomized Erectile Dysfunction Treatment [Baseline through 24 weeks]

   The reported reasons for a decision to discontinue from initial randomized treatment prior to Week 24 are reported. Discontinuation of randomized treatment was defined as switching between the 3 study treatments (tadalafil on demand, tadalafil once a day, or sildenafil citrate on demand) or discontinuing from all treatments. A change of dose within the same treatment was not considered as switching of treatment.

9. Number of Days From the 8-Week Study Visit to the Time the Participant Discontinues From All Phosphodiesterase Type 5 (PDE5) Inhibitor Treatments [8 weeks up to 334 days]

   The differences in time between the 8-week time point and the discontinuation of all study treatments (that is, discontinuation from the study and not switching to another treatment) are reported by the median (95% confidence interval). Duration was measured as the number of days from Week 8 to the date of the last dose of the study drug. This outcome measure was estimated using the Kaplan-Meier product-limit method.

10. Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Intercourse Satisfaction Domain [Baseline, 4, 8, 16, and 24 weeks]

    Self-reported intercourse satisfaction score over past 4 weeks (1 intercourse attempt item, 2 intercourse satisfaction items). Each item range: 0 (no intercourse attempts/no satisfaction) to 5 (more attempts/high satisfaction). Total scores range: 0-15; lower scores=lower intercourse satisfaction. Least Squares Mean changes from baseline to endpoint for each visit from repeated measures analysis and included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. Correlation matrix for repeated observations assumed to be unstructured.

11. Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Overall Satisfaction Domain [Baseline, 4, 8, 16, and 24 weeks]

    Self-reported overall satisfaction on the IIEF over past 4 weeks and consists of 2 questions (items 13 and 14), each rated on a scale from 1 (very dissatisfied) to 5 (very satisfied). Total scores range from 2 to 10; lower numerical scores represent lower overall satisfaction. Least Squares Mean changes from baseline to endpoint for each visit were from a repeated measures analysis and included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. The correlation matrix for the repeated observations was assumed to be unstructured.

12. Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) Questionnaire at 4, 8, 16, and 24 Weeks [4, 8, 16, and 24 weeks]

    The participant questionnaire consists of 11 questions. Each question is rated on a scale of 0 (extremely low treatment satisfaction) to 4 (extremely high treatment satisfaction). The EDITS summary score was obtained by adding each individual result for all questions, dividing by the number of questions answered (mean satisfaction score), then multiplying by 25, thus obtaining a score range from 0 (extremely low treatment satisfaction) to 100 (extremely high satisfaction). Least Squares Mean changes were adjusted for treatment group, country, visit, and visit*treatment.

13. Change From Baseline to 24 Week Endpoint of the Sexual Self-Confidence, Spontaneity, and Time Concerns Domains (23-items) of the Psychological and Interpersonal Relationships Scale (PAIRS) [Baseline, 24 weeks]

    The PAIRS is a 23-item scale that assesses broader psychological/interpersonal outcomes associated with erectile dysfunction and its treatment. Each question is rated on a Likert scale from 1 (strongly disagree) to 4 (strongly agree). The scale consists of 3 domains: Sexual Self-Confidence (items 1-6), Spontaneity domain (items 7-15), and Time Concerns (items 16-23). The average domain score for each domain was calculated by adding the nonmissing items for the respective domain, then dividing by the number of nonmissing items for the respective domain. Each average domain score ranged from 1 to 4. Higher scores represent the following: greater sexual self-confidence (better outcome); greater spontaneity (better outcome); higher time concerns (worse outcome). The Least Squares Mean changes were adjusted for treatment group, country, baseline IIEF-EF severity, baseline domain score, and baseline domain score*treatment (if p<0.10).

14. Change From Baseline to 4, 8, 16, and 24 Weeks of the Sexual Relationship Domain of the Self-Esteem and Relationship (SEAR) Questionnaire [Baseline, 4, 8, 16, and 24 weeks]

    SEAR assesses psychosocial outcomes in men with erectile dysfunction. 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 domain score was computed by summing its respective items, then transforming it into a 0 (least favorable) to 100 (most favorable) scale. Transformed score = 100 x [(actual raw score - lowest possible raw score)/possible raw score range]. Least Squares Mean changes adjusted for baseline score, treatment group, country, visit, and visit*treatment.

15. Change From Baseline to 4, 8, 16, and 24 Weeks of the Confidence Domain of the Self-Esteem and Relationship (SEAR) Questionnaire [Baseline, 4, 8, 16, and 24 weeks]

    SEAR assesses psychosocial outcomes in men with erectile dysfunction. Confidence domain measures improvement in confidence; 2 subscales (6 items: Self-Esteem [items 9-12]; Overall Relationship [items 13-14]). Each item range: 1 (Never) to 5 (Always); item 11 reverse scored. Domain score=sum of domain's respective items, then transformed into 0 (least favorable) to 100 (most favorable) scale. Transformed score=100x[(actual raw score-lowest possible raw score)/possible raw score range]. Least Squares Mean change adjusted for baseline score, treatment group, country, visit, and visit*treatment.

16. Change From Baseline to 4, 8, 16, and 24 Weeks of the Self Esteem Domain of the Self-Esteem and Relationship (SEAR) Questionnaire [Baseline, 4, 8, 16, and 24 weeks]

    SEAR assesses psychosocial outcomes in men with erectile dysfunction. The Self-Esteem domain consists of 4 items (items 9-12), each rated on a scale of 1 (Never) to 5 (Always). Item 11 is reverse scored (1=Always and 5=Never). The domain score was computed by summing its respective items, then transforming it into a 0 (least favorable) to 100 (most favorable) scale. The transformed score = 100 x [(actual raw score - lowest possible raw score)/possible raw score range]. Least Squares Mean changes were adjusted for baseline score, treatment group, country, visit, and visit*treatment.

17. Change From Baseline to 4, 8, 16, and 24 Weeks of the Overall Relationship Domain of the Self-Esteem and Relationship (SEAR) Questionnaire [Baseline, 4, 8, 16, and 24 weeks]

    SEAR assesses psychosocial outcomes in men with erectile dysfunction. The Overall Relationship domain consists of 2 items (items 13-14), each rated on a scale of 1 (Never) to 5 (Always). The domain score was computed by summing its respective items, then transforming it into a 0 (least favorable) to 100 (most favorable) scale. The transformed score = 100 x [(actual raw score - lowest possible raw score)/possible raw score range]. Least Squares Mean changes were adjusted for baseline score, treatment group, country, visit, and visit*treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of Erectile Dysfunction (ED) of at least 3 months duration.

• Anticipate having the same adult female sexual partner during the study.

• Agree not to use any other treatment for ED and to participate in recording responses to questionnaires and other instruments used in this study.

Exclusion Criteria:

• Previous or current treatment with tadalafil or any other phosphodiesterase type 5 (PDE5) inhibitor.

• ED caused by other primary sexual disorders, history of radical prostatectomy or other pelvic surgery with subsequent failure to achieve any erection, or history of penile implant or clinically significant penile deformity.

• ED caused by untreated or inadequately treated endocrine disease.

• Current treatment with doxazosin, nitrates, cancer chemotherapy, or anti-androgens.

• Severe renal or hepatic impairment, history of malignant hypertension.

• Presence or history of specific heart conditions.

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.	Carpentras		France	84200
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.	Chambery		France	73000
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.	La Bouexiere		France	35340
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.	Lille		France	59000
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.	Lyon		France	69437
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.	Marseille		France	13009
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.	Montpellier		France	34090
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.	Murs-Erigne		France	49610
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.	Nantes		France	44300
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.	Rennes		France	35 700
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.	Toulouse		France	31000
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.	Giengen		Germany	89537
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.	Grevenbroich		Germany	41515
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.	Holzminden		Germany	D-37603
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.	Koblenz		Germany	56068
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.	Leipzig		Germany	04109
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.	Leverkusen		Germany	51375
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.	Luebeck		Germany	23552
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.	Marburg		Germany	35039
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.	Muehlacker		Germany	D-75417
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.	Warburg		Germany	34414
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.	Heraklion		Greece	71110
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.	Larissa		Greece	41221
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.	Patras		Greece	26500
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.	Thessaloniki		Greece	56429
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.	Kutno		Poland	99-300
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.	Legionowo		Poland	05-120
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.	Lublin		Poland	20-008
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.	Warsaw		Poland	00-909
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.	Wroclaw		Poland	53-532
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.	Porto		Portugal	4202-451
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.	Bucharest		Romania	050653
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.	Cluj-Napoca		Romania	400046
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.	Alcorcon		Spain	28922
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.	Aravaca		Spain	28023
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.	Barcelona		Spain	08025
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.	Coslada		Spain	28820
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.	Gijon		Spain
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.	Madrid		Spain	28040
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.	Málaga		Spain	29007
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.	San Sebastian De Los Reyes		Spain	28702
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.	Vigo		Spain	36211
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.	Fowey	Cornwall	United Kingdom	PL23 1DT
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.	Durham	County Durham	United Kingdom	DH1 2QW
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.	Plymouth	Devon	United Kingdom	PL6 7TH

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: NCT01122264
• Other Study ID Numbers: 13085; H6D-EW-LVIJ
• First Posted: May 13, 2010
• Last Update Posted: Oct 19, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Eli Lilly and Company: Erectile Dysfunction
• Additional relevant MeSH terms: Erectile Dysfunction; Sildenafil Citrate; Tadalafil

Study Results

Participant Flow

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Period Title: Overall Study
STARTED	252	257	261
Received at Least 1 Dose of Study Drug	250	257	260
COMPLETED	220	228	214
NOT COMPLETED	32	29	47

Baseline Characteristics

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand	Total
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Total of all reporting groups
Overall Participants	252	257	261	770
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.2 (11.57)	52.9 (11.69)	53.0 (11.76)	53.0 (11.66)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	252 100%	257 100%	261 100%	770 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 0.8%	4 1.6%	4 1.5%	10 1.3%
White	248 98.4%	251 97.7%	254 97.3%	753 97.8%
More than one race	0 0%	0 0%	1 0.4%	1 0.1%
Unknown or Not Reported	2 0.8%	2 0.8%	2 0.8%	6 0.8%
Region of Enrollment (participants) [Number]
Portugal	6 2.4%	5 1.9%	7 2.7%	18 2.3%
France	99 39.3%	102 39.7%	100 38.3%	301 39.1%
Greece	9 3.6%	8 3.1%	9 3.4%	26 3.4%
Poland	15 6%	16 6.2%	16 6.1%	47 6.1%
Spain	48 19%	49 19.1%	52 19.9%	149 19.4%
Romania	20 7.9%	22 8.6%	21 8%	63 8.2%
Germany	45 17.9%	45 17.5%	47 18%	137 17.8%
United Kingdom	10 4%	10 3.9%	9 3.4%	29 3.8%

Outcome Measures

1. Primary Outcome

Title	Time to Discontinuation of Randomized Treatment
Description	Time to discontinuation of randomized treatment was defined as the number of days from randomization until the day the participant discontinued the randomized treatment. Discontinuation of randomized treatment was defined as switching between the 3 study treatments (tadalafil on demand, tadalafil once a day, or sildenafil citrate on demand) or discontinuing from all treatments. A change of dose within the same treatment was not considered switching of treatment. This outcome measure was estimated using the Kaplan-Meier product-limit method.
Time Frame	Baseline up to 334 days

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	252	257	261
Median (95% Confidence Interval) [days]	NA	130	67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil Once a Day, Sildenafil Citrate On Demand
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value: Tadalafil Once a Day versus Sildenafil Citrate On Demand treatment groups. Cox's proportional hazards model with factors for randomized treatment group, baseline International Index of Erectile Function-Erectile Function score, and country.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 97.3%; 0.51 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tadalafil On Demand, Sildenafil Citrate On Demand
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	P-value: Tadalafil On Demand versus Sildenafil Citrate On Demand treatment groups. Cox's proportional hazards model with factors for randomized treatment group, baseline International Index of Erectile Function-Erectile Function score, and country.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 97.3%; 0.37 to 0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tadalafil On Demand, Tadalafil Once a Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments	P-value: Tadalafil On Demand versus Tadalafil Once a Day treatment groups using Cox's proportional hazards model with factors for randomized treatment group, baseline International Index of Erectile Function-Erectile Function score, and country.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 1.02 to 1.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Erectile Function (EF) Domain
Description	Self-reported EF score over past 4 weeks. Items 1-5 scores range from 0 (no sexual activity) to 5 (high EF). Item 15 score ranges from 1 (very low confidence to get/keep erection) to 5 (very high confidence). Total scores range from 1 to 30; lower scores denote greater erectile dysfunction severity. Least Squares Mean changes from baseline to endpoint for each visit from repeated measures analysis included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. Correlation matrix for repeated observations assumed to be unstructured.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline IIEF-EF observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	241	251	250
Change from Baseline to Week 4	7.92 (0.44)	8.60 (0.43)	8.86 (0.43)
Change from Baseline to Week 8 (n=231, 232, 232)	8.98 (0.45)	9.08 (0.45)	9.70 (0.44)
Change from Baseline to Week 16 (n=167, 146, 101)	10.60 (0.41)	9.93 (0.42)	10.56 (0.45)
Change from Baseline to Week 24 (n=141, 116, 81)	10.70 (0.43)	10.01 (0.45)	11.05 (0.49)

3. Secondary Outcome

Title	Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Orgasmic Function Domain
Description	Self-reported orgasmic function on the IIEF over past 4 weeks and consists of 2 questions (items 9 and 10). Each question is rated on a scale from 0 (no sexual stimulation) to 5 (almost always/always). Total scores range from 0 to 10; lower scores represent lower orgasmic function. Least Squares Mean changes from baseline to endpoint for each visit were from a repeated measures analysis and included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. The correlation matrix for the repeated observations was assumed to be unstructured.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline IIEF Orgasmic Function observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	241	251	250
Change from Baseline to Week 4	1.64 (0.16)	1.75 (0.16)	1.92 (0.16)
Change from Baseline to Week 8 (n=231, 232, 232)	1.77 (0.16)	2.08 (0.16)	2.26 (0.16)
Change from Baseline to Week 16 (n=167, 146, 101)	2.37 (0.15)	2.25 (0.16)	2.66 (0.17)
Change from Baseline to Week 24 (n=141, 116, 81)	2.55 (0.15)	2.48 (0.16)	2.62 (0.18)

4. Secondary Outcome

Title	Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Sexual Desire Domain
Description	Self-reported sexual desire on IIEF over past 4 weeks; comprises 2 questions (items 11 and 12). Each question rated on a scale from 1 (almost never or low/no sexual desire) to 5 (almost always or very high sexual desire). Total scores range: 2 to 10; lower numerical scores denote lower sexual desire. Least Squares Mean changes from baseline to endpoint for each visit from repeated measures analysis and included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. Correlation matrix for repeated observations assumed to be unstructured.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline IIEF Sexual Desire observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	244	250	249
Change from Baseline to 4 Weeks	0.77 (0.10)	0.75 (0.10)	0.69 (0.10)
Change from Baseline to 8 Weeks (n=230, 232, 232)	0.96 (0.11)	0.90 (0.11)	0.87 (0.11)
Change from Baseline to 16 Weeks (n=167, 146, 101)	1.15 (0.12)	0.87 (0.12)	1.07 (0.14)
Change from Baseline to 24 Weeks (n=140, 117, 81)	1.19 (0.12)	0.78 (0.13)	1.29 (0.14)

5. Secondary Outcome

Title	Change From Baseline to 4, 8, 16 and 24 Weeks 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 specified period of time. SEP Q1-Q5 scores determined as percentage of 'Yes' responses to each of 5 questions out of all sexual attempts recorded during the time period. Least Squares Mean changes from baseline to endpoint for each visit from a repeated measures analysis included terms for baseline score, treatment group, country, visit, and visit*treatment.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline SEP observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	242	246	248
Q1:Change from Baseline to 4 Weeks	14.50	18.49	18.41
Q1:Change from Baseline to 8 Weeks (n=224,231,229)	16.62	19.88	20.41
Q1:Change from Baseline to 16 Weeks (n=166,146,99)	18.46	19.19	20.58
Q1:Change from Baseline to 24 Weeks (n=139,115,81)	19.97	19.60	20.34
Q2:Change from Baseline to 4 Weeks	27.48	28.56	29.64
Q2:Change from Baseline to 8 Weeks (n=224,231,229)	31.16	31.66	34.08
Q2:Change from Baseline to 16 Weeks (n=166,146,99)	32.76	32.76	36.07
Q2:Change from Baseline to 24 Weeks (n=139,115,81)	35.83	34.70	35.93
Q3:Change from Baseline to 4 Weeks	41.52	41.76	44.45
Q3:Change from Baseline to 8 Weeks (n=224,231,229)	47.45	44.58	52.11
Q3:Change from Baseline to 16 Weeks (n=166,146,99)	54.26	50.62	56.96
Q3:Change from Baseline to 24 Weeks (n=139,115,81)	56.39	53.83	56.28
Q4:Change from Baseline to 4 Weeks	49.59	51.78	51.45
Q4:Change from Baseline to 8 Weeks (n=224,231,229)	60.86	55.59	59.28
Q4:Change from Baseline to 16 Weeks (n=166,146,99)	66.17	63.00	66.48
Q4:Change from Baseline to 24 Weeks (n=139,115,81)	72.67	68.06	69.04
Q5:Change from Baseline to 4 Weeks	46.12	45.71	49.63
Q5:Change from Baseline to 8 Weeks (n=224,231,229)	53.92	50.06	55.73
Q5:Change from Baseline to 16 Weeks (n=166,146,99)	61.57	54.56	62.40
Q5:Change from Baseline to 24 Weeks (n=139,115,81)	65.45	62.17	66.57

6. Secondary Outcome

Title	Global Assessment Questions (GAQ)
Description	The GAQ consists of 2 Yes/No/No Response (No Respo) questions. GAQ Question (Q)1: Has the treatment you have been taking during this study improved your erections? GAQ Q2: Has the treatment improved your ability to engage in sexual activity?
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants. The last available GAQ assessment for each participant was used in the analysis.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	252	257	261
Q1:Treatment improved erections? Yes	218 86.5%	219 85.2%	203 77.8%
Q1:Treatment improved erections? No	20 7.9%	23 8.9%	34 13%
Q1: Treatment improved erections? No Response	14 5.6%	15 5.8%	24 9.2%
Q2:Treatment improved ability to engage? Yes	209 82.9%	214 83.3%	204 78.2%
Q2:Treatment improved ability to engage? No	14 5.6%	7 2.7%	8 3.1%
Q2: Treatment improved ability to engage? No Respo	29 11.5%	36 14%	49 18.8%

7. Secondary Outcome

Title	Number of Treatment Switches
Description	The number of times participants switched erectile dysfunction medication within the 3 treatments being studied (tadalafil on demand, tadalafil once a day, or sildenafil citrate on demand).
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who switched erectile dysfunction medication and had a baseline and post-baseline observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	87	120	151
Mean (Standard Deviation) [number of treatment switches]	1.2 (0.4)	1.2 (0.5)	1.3 (0.5)

8. Secondary Outcome

Title	Patterns of Erectile Dysfunction Treatment Change
Description	Results are reported as the number of participants per sequence of study medications (tadalafil on demand, tadalafil once a day, or sildenafil citrate on demand) that were taken as a result of switching treatments. The Other Treatment Sequence reports the number of participants per sequence of study medications that were taken as a result of switching treatments more than once. The number of participants who did not switch is also reported.
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

All randomly assigned participants were included in the analysis.

Arm/Group Title	Entire Study Population
Arm/Group Description	Tadalafil On Demand: Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day). Tadalafil Once a Day: Participants were instructed to take a 5-mg or 2.5-mg tadalafil tablet orally, once a day. Sildenafil Citrate On Demand: Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day).
Measure Participants	770
No Treatment Intake	3 1.2%
No Switch	409 162.3%
From Once a Day to Any On Demand	95 37.7%
From Any On Demand to Once a Day	84 33.3%
From Any On Demand to Any On Demand	97 38.5%
Returning Back to Randomized Treatment	35 13.9%
Other Treatment Sequence	47 18.7%

9. Secondary Outcome

Title	Reasons for Discontinuation of Randomized Erectile Dysfunction Treatment
Description	The reported reasons for a decision to discontinue from initial randomized treatment prior to Week 24 are reported. Discontinuation of randomized treatment was defined as switching between the 3 study treatments (tadalafil on demand, tadalafil once a day, or sildenafil citrate on demand) or discontinuing from all treatments. A change of dose within the same treatment was not considered as switching of treatment.
Time Frame	Baseline through 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	252	257	261
Slow onset of action	5 2%	9 3.5%	10 3.8%
Completed treatment	1 0.4%	1 0.4%	1 0.4%
Lack of efficacy (hardness of erection)	46 18.3%	55 21.4%	55 21.1%
Lack of efficacy (duration of erection)	7 2.8%	11 4.3%	24 9.2%
Lack of confidence in medication working each time	3 1.2%	5 1.9%	2 0.8%
Adverse event	7 2.8%	10 3.9%	16 6.1%
Feel medication controls my sexual life	1 0.4%	0 0%	7 2.7%
Non-desired spontaneous erections	2 0.8%	4 1.6%	0 0%
Time constraints due to short drug action window	1 0.4%	0 0%	11 4.2%
Partner's request	0 0%	2 0.8%	3 1.1%
Don't want to take a pill every day	0 0%	27 10.5%	0 0%
Prefer a pill every day, not on demand	20 7.9%	0 0%	28 10.7%
Participant discontinuation from the trial	11 4.4%	11 4.3%	14 5.4%
Participant did not take any study drug	2 0.8%	0 0%	1 0.4%
Participants without discontinuation event	146 57.9%	122 47.5%	89 34.1%

10. Secondary Outcome

Title	Number of Days From the 8-Week Study Visit to the Time the Participant Discontinues From All Phosphodiesterase Type 5 (PDE5) Inhibitor Treatments
Description	The differences in time between the 8-week time point and the discontinuation of all study treatments (that is, discontinuation from the study and not switching to another treatment) are reported by the median (95% confidence interval). Duration was measured as the number of days from Week 8 to the date of the last dose of the study drug. This outcome measure was estimated using the Kaplan-Meier product-limit method.
Time Frame	8 weeks up to 334 days

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who completed the 8-week randomized treatment.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day).	Participants were instructed to take a 5-mg or 2.5-mg tadalafil tablet orally, once a day.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day).
Measure Participants	234	238	236
Median (95% Confidence Interval) [days]	NA	NA	187

11. Secondary Outcome

Title	Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Intercourse Satisfaction Domain
Description	Self-reported intercourse satisfaction score over past 4 weeks (1 intercourse attempt item, 2 intercourse satisfaction items). Each item range: 0 (no intercourse attempts/no satisfaction) to 5 (more attempts/high satisfaction). Total scores range: 0-15; lower scores=lower intercourse satisfaction. Least Squares Mean changes from baseline to endpoint for each visit from repeated measures analysis and included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. Correlation matrix for repeated observations assumed to be unstructured.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline IIEF Intercourse Satisfaction observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	242	251	251
Change from Baseline to Week 4	3.21 (0.20)	3.22 (0.20)	3.53 (0.20)
Change from Baseline to Week 8 (n=231, 232, 232)	3.69 (0.20)	3.15 (0.20)	3.95 (0.20)
Change from Baseline to Week 16 (n=167, 146, 101)	4.38 (0.20)	3.60 (0.21)	4.41 (0.23)
Change from Baseline to Week 24 (n=141, 116, 81)	4.48 (0.21)	3.71 (0.22)	4.70 (0.24)

12. Secondary Outcome

Title	Change From Baseline to 4, 8, 16 and 24 Weeks of the International Index of Erectile Function (IIEF) Overall Satisfaction Domain
Description	Self-reported overall satisfaction on the IIEF over past 4 weeks and consists of 2 questions (items 13 and 14), each rated on a scale from 1 (very dissatisfied) to 5 (very satisfied). Total scores range from 2 to 10; lower numerical scores represent lower overall satisfaction. Least Squares Mean changes from baseline to endpoint for each visit were from a repeated measures analysis and included terms for baseline score, treatment group, country, baseline*treatment (if p<0.10), visit, and visit*treatment. The correlation matrix for the repeated observations was assumed to be unstructured.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline IIEF Overall Satisfaction observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	245	250	251
Change from Baseline to Week 4	2.46 (0.16)	2.58 (0.15)	2.72 (0.15)
Change from Baseline to Week 8 (n=230, 231, 233)	2.80 (0.16)	2.85 (0.16)	2.98 (0.16)
Change from Baseline to Week 16 (n=167, 145, 101)	3.34 (0.15)	3.09 (0.15)	3.48 (0.17)
Change from Baseline to Week 24 (n=141, 116, 81)	3.50 (0.15)	3.24 (0.16)	3.41 (0.17)

13. Secondary Outcome

Title	Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) Questionnaire at 4, 8, 16, and 24 Weeks
Description	The participant questionnaire consists of 11 questions. Each question is rated on a scale of 0 (extremely low treatment satisfaction) to 4 (extremely high treatment satisfaction). The EDITS summary score was obtained by adding each individual result for all questions, dividing by the number of questions answered (mean satisfaction score), then multiplying by 25, thus obtaining a score range from 0 (extremely low treatment satisfaction) to 100 (extremely high satisfaction). Least Squares Mean changes were adjusted for treatment group, country, visit, and visit*treatment.
Time Frame	4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline EDITS observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	246	252	249
EDITS at Week 4	72.36	75.20	71.98
EDITS at Week 8 (n=231, 235, 231)	75.28	76.64	72.74
EDITS at Week 16 (n=168, 147, 100)	79.64	77.66	76.64
EDITS at Week 24 (n=141, 118, 80)	81.01	78.75	77.98

14. Secondary Outcome

Title	Change From Baseline to 24 Week Endpoint of the Sexual Self-Confidence, Spontaneity, and Time Concerns Domains (23-items) of the Psychological and Interpersonal Relationships Scale (PAIRS)
Description	The PAIRS is a 23-item scale that assesses broader psychological/interpersonal outcomes associated with erectile dysfunction and its treatment. Each question is rated on a Likert scale from 1 (strongly disagree) to 4 (strongly agree). The scale consists of 3 domains: Sexual Self-Confidence (items 1-6), Spontaneity domain (items 7-15), and Time Concerns (items 16-23). The average domain score for each domain was calculated by adding the nonmissing items for the respective domain, then dividing by the number of nonmissing items for the respective domain. Each average domain score ranged from 1 to 4. Higher scores represent the following: greater sexual self-confidence (better outcome); greater spontaneity (better outcome); higher time concerns (worse outcome). The Least Squares Mean changes were adjusted for treatment group, country, baseline IIEF-EF severity, baseline domain score, and baseline domain score*treatment (if p<0.10).
Time Frame	Baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline PAIRS observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	252	257	261
Sexual Self-Confidence Domain (n=196, 203, 185)	0.93	0.90	0.73
Spontaneity Domain (n=197, 202, 186)	0.13	0.11	0.02
Time Concerns Domain (n=196, 200, 184)	-0.08	-0.20	0.04

15. Secondary Outcome

Title	Change From Baseline to 4, 8, 16, and 24 Weeks of the Sexual Relationship Domain of the Self-Esteem and Relationship (SEAR) Questionnaire
Description	SEAR assesses psychosocial outcomes in men with erectile dysfunction. 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 domain score was computed by summing its respective items, then transforming it into a 0 (least favorable) to 100 (most favorable) scale. Transformed score = 100 x [(actual raw score - lowest possible raw score)/possible raw score range]. Least Squares Mean changes adjusted for baseline score, treatment group, country, visit, and visit*treatment.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline SEAR Sexual Relationship observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	244	250	246
Change from Baseline to Week 4	27.65	29.26	29.50
Change from Baseline to Week 8 (n=230, 232, 231)	31.42	31.07	31.15
Change from Baseline to Week 16 (n=167, 146, 101)	37.59	32.90	37.32
Change from Baseline to Week 24 (n=140, 117, 81)	39.37	34.96	37.46

16. Secondary Outcome

Title	Change From Baseline to 4, 8, 16, and 24 Weeks of the Confidence Domain of the Self-Esteem and Relationship (SEAR) Questionnaire
Description	SEAR assesses psychosocial outcomes in men with erectile dysfunction. Confidence domain measures improvement in confidence; 2 subscales (6 items: Self-Esteem [items 9-12]; Overall Relationship [items 13-14]). Each item range: 1 (Never) to 5 (Always); item 11 reverse scored. Domain score=sum of domain's respective items, then transformed into 0 (least favorable) to 100 (most favorable) scale. Transformed score=100x[(actual raw score-lowest possible raw score)/possible raw score range]. Least Squares Mean change adjusted for baseline score, treatment group, country, visit, and visit*treatment.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline SEAR Confidence observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	245	251	247
Change from Baseline to Week 4	23.43	23.04	25.03
Change from Baseline to Week 8 (n=230, 233, 232)	26.97	26.10	27.14
Change from Baseline to Week 16 (n=167, 147, 100)	33.15	28.33	31.86
Change from Baseline to Week 24 (n=140, 116, 81)	33.74	30.42	31.66

17. Secondary Outcome

Title	Change From Baseline to 4, 8, 16, and 24 Weeks of the Self Esteem Domain of the Self-Esteem and Relationship (SEAR) Questionnaire
Description	SEAR assesses psychosocial outcomes in men with erectile dysfunction. The Self-Esteem domain consists of 4 items (items 9-12), each rated on a scale of 1 (Never) to 5 (Always). Item 11 is reverse scored (1=Always and 5=Never). The domain score was computed by summing its respective items, then transforming it into a 0 (least favorable) to 100 (most favorable) scale. The transformed score = 100 x [(actual raw score - lowest possible raw score)/possible raw score range]. Least Squares Mean changes were adjusted for baseline score, treatment group, country, visit, and visit*treatment.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline SEAR Self-Esteem observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	245	251	247
Change from Baseline to 4 Weeks	25.18	24.10	26.59
Change from Baseline to 8 Weeks (n=230, 233, 233)	29.14	27.80	28.92
Change from Baseline to 16 Weeks (n=167, 147, 100)	35.23	29.46	33.85
Change from Baseline to 24 Weeks (n=140, 116, 81)	35.86	31.14	33.52

18. Secondary Outcome

Title	Change From Baseline to 4, 8, 16, and 24 Weeks of the Overall Relationship Domain of the Self-Esteem and Relationship (SEAR) Questionnaire
Description	SEAR assesses psychosocial outcomes in men with erectile dysfunction. The Overall Relationship domain consists of 2 items (items 13-14), each rated on a scale of 1 (Never) to 5 (Always). The domain score was computed by summing its respective items, then transforming it into a 0 (least favorable) to 100 (most favorable) scale. The transformed score = 100 x [(actual raw score - lowest possible raw score)/possible raw score range]. Least Squares Mean changes were adjusted for baseline score, treatment group, country, visit, and visit*treatment.
Time Frame	Baseline, 4, 8, 16, and 24 weeks

Outcome Measure Data

Analysis Population Description

The analysis included all randomly assigned participants who had a baseline and post-baseline SEAR Overall Relationship observation.

Arm/Group Title	Tadalafil On Demand	Tadalafil Once a Day	Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.	Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.	Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
Measure Participants	244	251	247
Change from Baseline to Week 4	19.92	21.10	22.00
Change from Baseline to Week 8 (n=229, 232, 232)	22.75	22.96	23.74
Change from Baseline to Week 16 (n=166, 147, 100)	29.63	26.96	28.57
Change from Baseline to Week 24 (n=139, 116, 81)	30.28	29.93	28.74

Adverse Events

Arm/Group Title	Tadalafil On Demand		Tadalafil Once a Day		Sildenafil Citrate On Demand
Arm/Group Description	Participants were instructed to take a 10-milligram (mg) or 20-mg tablet of tadalafil orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.		Participants were instructed to take a 5-mg or 2.5-mg tablet of tadalafil orally once a day for 24 weeks.		Participants were instructed to take a 50-mg, 100-mg, or 25-mg tablet of sildenafil citrate orally on demand, with a maximum of 4 tablets per week (and no more than 1 tablet per day) for 24 weeks.
All Cause Mortality
	Tadalafil On Demand		Tadalafil Once a Day		Sildenafil Citrate On Demand
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tadalafil On Demand		Tadalafil Once a Day		Sildenafil Citrate On Demand
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/250 (3.2%)		4/257 (1.6%)		2/260 (0.8%)
Congenital, familial and genetic disorders
Congenital, familial and genetic disorders	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Pulmonary sequestration	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Gastrointestinal disorders
Gastrointestinal disorders	0/250 (0%)	0	1/257 (0.4%)	1	0/260 (0%)	0
Pancreatitis acute	0/250 (0%)	0	1/257 (0.4%)	1	0/260 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/250 (0%)	0	1/257 (0.4%)	1	0/260 (0%)	0
Hepatobiliary disorders	0/250 (0%)	0	1/257 (0.4%)	1	0/260 (0%)	0
Infections and infestations
Diverticulitis	1/250 (0.4%)	2	0/257 (0%)	0	0/260 (0%)	0
Infections and infestations	2/250 (0.8%)	3	0/257 (0%)	0	0/260 (0%)	0
Parotitis	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/250 (0%)	0	0/257 (0%)	0	1/260 (0.4%)	1
Metabolism and nutrition disorders	0/250 (0%)	0	0/257 (0%)	0	1/260 (0.4%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/250 (0.4%)	5	0/257 (0%)	0	0/260 (0%)	0
Musculoskeletal and connective tissue disorders	1/250 (0.4%)	5	0/257 (0%)	0	0/260 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic	0/250 (0%)	0	1/257 (0.4%)	1	0/260 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)	2/250 (0.8%)	2	1/257 (0.4%)	1	1/260 (0.4%)	2
Oesophageal neoplasm	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Pituitary tumour benign	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Prostate cancer	0/250 (0%)	0	0/257 (0%)	0	1/260 (0.4%)	2
Psychiatric disorders
Completed suicide	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Psychiatric disorders	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Renal and urinary disorders
Renal and urinary disorders	0/250 (0%)	0	0/257 (0%)	0	1/260 (0.4%)	1
Urinary retention	0/250 (0%)	0	0/257 (0%)	0	1/260 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Respiratory, thoracic and mediastinal disorders	1/250 (0.4%)	1	0/257 (0%)	0	0/260 (0%)	0
Surgical and medical procedures
Spinal laminectomy	0/250 (0%)	0	1/257 (0.4%)	1	0/260 (0%)	0
Surgical and medical procedures	0/250 (0%)	0	1/257 (0.4%)	1	0/260 (0%)	0
Vascular disorders
Vascular disorders	1/250 (0.4%)	2	0/257 (0%)	0	0/260 (0%)	0
Venous insufficiency	1/250 (0.4%)	2	0/257 (0%)	0	0/260 (0%)	0
Other (Not Including Serious) Adverse Events
	Tadalafil On Demand		Tadalafil Once a Day		Sildenafil Citrate On Demand
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	106/250 (42.4%)		80/257 (31.1%)		103/260 (39.6%)
Gastrointestinal disorders
Gastrointestinal disorders	21/250 (8.4%)	52	30/257 (11.7%)	79	10/260 (3.8%)	32
Infections and infestations
Infections and infestations	17/250 (6.8%)	27	10/257 (3.9%)	22	10/260 (3.8%)	17
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	44/250 (17.6%)	117	19/257 (7.4%)	51	40/260 (15.4%)	110
Intentional overdose	16/250 (6.4%)	40	5/257 (1.9%)	12	8/260 (3.1%)	26
Overdose	21/250 (8.4%)	56	8/257 (3.1%)	24	23/260 (8.8%)	63
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	16/250 (6.4%)	45	17/257 (6.6%)	33	9/260 (3.5%)	20
Nervous system disorders
Headache	10/250 (4%)	30	14/257 (5.4%)	32	23/260 (8.8%)	49
Nervous system disorders	14/250 (5.6%)	36	19/257 (7.4%)	41	27/260 (10.4%)	60
Vascular disorders
Vascular disorders	11/250 (4.4%)	37	3/257 (1.2%)	7	17/260 (6.5%)	46

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.