A Study of Tadalafil and Sildenafil in Men With Erectile Dysfunction in China

• ClinicalTrials.gov Identifier: NCT01352507
• Recruitment Status: Completed
• First Posted: May 12, 2011
• Results First Posted: April 26, 2013
• Last Update Posted: April 26, 2013
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Erectile Dysfunction
• Interventions: Drug: Tadalafil; Drug: Sildenafil
• Enrollment: 383

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Tadalafil Then Sildenafil	Sildenafil Then Tadalafil
Arm/Group Description	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks, followed by 100 mg sildenafil taken orally, as needed, for an additional 8 weeks. There was a washout period of 7 to 10 days between treatments. At the end of the two 8-week treatment periods, participants were allowed to enter an 8-week extension phase on their preferred medication for erectile dysfunction (ED).	100 mg sildenafil taken orally, as needed, for 8 weeks, followed by 20 mg tadalafil taken orally, as needed, for an additional 8 weeks. There was a washout period of 7 to 10 days between treatments. At the end of the two 8-week treatment periods, participants were allowed to enter an 8-week extension phase on their preferred medication for ED.
Period Title: Treatment Period 1
Started	190	193
Received Treatment	182	188
Completed	176	184
Not Completed	14	9
Reason Not Completed
Adverse Event	3	0
Lost to Follow-up	3	4
Withdrawal by Subject	7	5
Physician Decision	1	0
Period Title: Washout Period
Started	176	184
Completed	176	183
Not Completed	0	1
Reason Not Completed
Withdrawal by Subject	0	1
Period Title: Treatment Period 2
Started	176	183
Received Treatment	173	181
Completed	170 [1]	180 [2]
Not Completed	6	3
Reason Not Completed
Entry Criteria Not Met	1	0
Withdrawal by Subject	4	3
Lack of Efficacy	1	0
[1] Six participants who completed Treatment Period 2 chose not to enter the Extension Phase.; [2] Seven participants who completed Treatment Period 2 chose not to enter the Extension Phase.
Period Title: Extension Phase
Started	164	173
Completed	164	173
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Tadalafil Then Sildenafil	Sildenafil Then Tadalafil	Total
Arm/Group Description		20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks, followed by 100 mg sildenafil taken orally, as needed, for an additional 8 weeks. There was a washout period of 7 to 10 days between treatments. At the end of the two 8-week treatment periods, participants were allowed to enter an 8-week extension phase on their preferred medication for erectile dysfunction (ED).	100 mg sildenafil taken orally, as needed, for 8 weeks, followed by 20 mg tadalafil taken orally, as needed, for an additional 8 weeks. There was a washout period of 7 to 10 days between treatments. At the end of the two 8-week treatment periods, participants were allowed to enter an 8-week extension phase on their preferred medication for ED.	Total of all reporting groups
Overall Number of Baseline Participants		190	193	383
Baseline Analysis Population Description		All randomized participants.
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	190 participants	193 participants	383 participants
		39.20 (10.52)	40.66 (11.44)	39.94 (11.00)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	190 participants	193 participants	383 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	190 100.0%	193 100.0%	383 100.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants
Chinese	Number Analyzed	190 participants	193 participants	383 participants
		190	193	383
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
China	Number Analyzed	190 participants	193 participants	383 participants
		190	193	383
International Index of Erectile Function (IIEF) Erectile Function (EF) Domain [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	190 participants	193 participants	383 participants
		13.77 (5.37)	14.19 (6.08)	13.98 (5.73)
		[1] Measure Description: IIEF-EF was the sum of Questions (Q)1 through 5 and Q15 of the IIEF. Q1 to Q5 were scored 0 (low/no erectile function) to 5 (high erectile function) and Q15 was scored 1 (no/low confidence) to 5 (high confidence). IIEF-EF domain scores ranged from 1 to 30. Higher scores represented better erectile function.
Erectile Dysfunction (ED) Severity [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	190 participants	193 participants	383 participants
Mild		63	68	131
Moderate		68	65	133
Severe		59	60	119
		[1] Measure Description: Investigator-reported severity of a participant's ED. ED was defined as a consistent change in the quality of erection adversely affecting participant satisfaction with sexual intercourse. Severity was based on investigator opinion.
ED Duration; Measure Type: Number; Unit of measure: Participants	Number Analyzed	190 participants	193 participants	383 participants
≥3 months to <1 year		77	87	164
≥1 year		113	106	219
ED Etiology; Measure Type: Number; Unit of measure: Participants	Number Analyzed	190 participants	193 participants	383 participants
Psychogenic		46	41	87
Organic		11	13	24
Mixed		133	139	272

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Preferring Tadalafil Over Sildenafil Measured at Week 18 Using Question 1 of the "Phosphodiesterase 5 Inhibitor Treatment Preference" Questionnaire (PITPQ)
Description	PITPQ Question (Q) 1 was a dichotomous outcome measure in which the participant selected his preferred study treatment (tadalafil or sildenafil) to receive during the Extension Phase.
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants who completed both treatment periods (Week 18), responded to the PITPQ, and were analyzed according to their assigned treatment.

Arm/Group Title	All Randomized Participants
Arm/Group Description:	Includes participants randomized to initially receive tadalafil (20 mg taken orally, as needed, for 8 weeks) and participants randomized to initially receive sildenafil (100 mg taken orally, as needed, for 8 weeks).
Overall Number of Participants Analyzed	350
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	69.1; (64 to 74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Randomized Participants
	Comments	Null hypothesis (H0): The proportion of participants who chose tadalafil over sildenafil is equal to 0.5 (p = 0.5), versus alternative hypothesis (H1): p is not equal to 0.5 (2-sided test).
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Wilson Score method
	Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants Moderately or Strongly Preferring the Selected Treatment at Week 18 Using Question 2 of the PITPQ
Description	PITPQ Q2 was a measure of the degree of treatment preference based on the participant's opinion. The question was, "For the treatment preference you selected in Q1, what is your degree of preference?". Choices were moderate or strong.
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants who completed both treatment periods (Week 18), responded to the PITPQ, and were analyzed according to their assigned treatment.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	Participants who preferred tadalafil over sildenafil.	Participants who preferred sildenafil over tadalafil.
Overall Number of Participants Analyzed	242	108
Measure Type: Number; Unit of Measure: percentage of participants
Strong preference	38.0	34.3
Moderate preference	62.0	65.7

3. Secondary Outcome

Title	Change in International Index of Erectile Function (IIEF) Overall Satisfaction Domain
Description	Self-reported overall satisfaction over the past 4 weeks. IIEF overall satisfaction was the sum of Q13 and Q14. Scores ranged from 1 (low/no satisfaction) to 5 (high satisfaction) for each question, with the total possible score for the 2 questions ranging from 2 to 10. Change was defined as endpoint minus baseline domain score. Change in IIEF overall satisfaction domain at Week 8 and Week 18 were averaged to produce an overall change in IIEF overall satisfaction domain score. Higher IIEF overall satisfaction domain scores were indicative of greater overall satisfaction.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least 1 IIEF post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	355	354
Mean (Standard Deviation); Unit of Measure: units on a scale
	3.74 (1.94)	3.71 (2.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.793
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Squares (LS) mean difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.15
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change in Sexual Encounter Profile (SEP) Question 2
Description	Participant-assessed diary that assessed the mean change from baseline in the percentage of "yes" responses to SEP Q2, "Were you able to insert your penis into your partner's vagina?". The SEP Q2 score was determined as the percentage of "yes" responses to SEP Q2 out of all sexual attempts recorded during the time period. Change was defined as the percentage of "yes" responses at endpoint minus the percentage of "yes" responses at baseline. Change in percentage of "yes" responses to SEP Q2 at Week 8 and Week 18 were averaged to produce an overall change in SEP Q2.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants with baseline and at least 1 post-baseline SEP measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	356	354
Mean (Standard Deviation); Unit of Measure: percentage of "yes" responses
	45.28 (42.03)	44.94 (41.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.988
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -1.35 to 1.37
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change in Psychosocial and Interpersonal Relationship Scale (PAIRS) Sexual Self-Confidence Domain
Description	PAIRS was a self-administered, 29-item scale that assessed the broader psychological and interpersonal outcomes associated with ED and its treatment. Each question was rated on a Likert scale that ranged from 1 (strongly disagree) to 4 (strongly agree). The sexual self-confidence domain score was the average score for Items 5, 10, 15, 23, 27, and 29. Sexual self-confidence domain scores ranged from 1 (strongly disagree) to 4 (strongly agree). Change was defined as endpoint minus baseline domain score. Change in PAIRS sexual self-confidence domain scores at Week 8 and Week 18 were averaged to produce an overall change in PAIRS sexual self-confidence domain score. Higher scores were indicative of greater sexual self-confidence.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants with baseline and at least 1 PAIRS post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 mg tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	355	354
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.75 (0.65)	0.72 (0.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.102
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.08
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Drug Attributes Questionnaire (DRAQ) at Week 18
Description	DRAQ was a questionnaire used to record explanations for why participants preferred a drug. Participants identified their first and second reasons for drug preference from a choice of 7 reasons. Each reason for drug preference includes participants who selected that reason as their first or second reason.
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants who completed both treatment periods (Week 18), responded to the DRAQ, and were analyzed according to their assigned treatment.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	Participants who preferred tadalafil over sildenafil.	Participants who preferred sildenafil over tadalafil.
Overall Number of Participants Analyzed	242	108
Measure Type: Number; Unit of Measure: percentage of participants
Time between drug and first erection was short	10.3	35.2
Was able to get an erection long after having drug	55.0	11.1
Had erections the next morning	24.0	11.1
The firmness of erections	36.4	51.9
Was able to get an erection every time	37.6	56.5
Had few side effects	23.6	25.9
Partner preferred this treatment	10.7	7.4

7. Secondary Outcome

Title	Change in International Index of Erectile Function (IIEF) Intercourse Satisfaction Domain
Description	Self-reported intercourse satisfaction over the past 4 weeks. IIEF intercourse satisfaction was the sum of Q6, Q7, and Q8 of the IIEF. Scores ranged from 0 (low/no satisfaction) to 5 (high satisfaction) for each question, with the total possible score for the 3 questions ranging from 0 to 15. Change was defined as endpoint minus baseline domain score. Change in IIEF intercourse satisfaction domain at Week 8 and Week 18 were averaged to produce an overall change in IIEF intercourse satisfaction domain score. Higher scores were indicative of an increase in intercourse satisfaction.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least 1 IIEF post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	355	354
Mean (Standard Deviation); Unit of Measure: units on a scale
	5.88 (3.02)	5.91 (3.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.861
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.19
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Change in International Index of Erectile Function (IIEF) Sexual Desire Domain
Description	Self-reported sexual desire over the past 4 weeks. IIEF sexual desire was the sum of Q11 and Q12. Scores ranged from 1 (low/almost never) to 5 (very high/almost always) for each question, with the total possible score for the 2 questions ranging from 2 to 10. Change was defined as endpoint minus baseline domain score. Change in IIEF sexual desire domain at Week 8 and Week 18 were averaged to produce an overall change in IIEF sexual desire domain score. Higher scores were indicative of increased sexual desire.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants with baseline and at least 1 IIEF post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	355	354
Mean (Standard Deviation); Unit of Measure: units on a scale
	2.55 (2.11)	2.60 (2.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.495
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.09
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Change in International Index of Erectile Function (IIEF) Orgasmic Function Domain
Description	Self-reported orgasmic function over the past 4 weeks. IIEF orgasmic function was the sum of Q9 and Q10 of the IIEF. Scores ranged from 0 (no stimulation) to 5 (almost always) for each question, with the total possible score for the 2 questions ranging from 0 to 10. Change was defined as endpoint minus baseline domain score. Change in IIEF orgasmic function domain at Week 8 and Week 18 were averaged to produce an overall change in IIEF orgasmic function domain score. Higher scores were indicative of better orgasmic function.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants with baseline and at least 1 IIEF post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	355	354
Mean (Standard Deviation); Unit of Measure: units on a scale
	3.70 (2.82)	3.71 (2.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.917
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.16
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change in Sexual Encounter Profile (SEP) Question 3
Description	Participant-assessed diary that assessed the mean change from baseline in the percentage of "yes" responses to SEP Q3, "Did your erection last long enough for you to have successful intercourse?". The SEP Q3 score was determined as the percentage of "yes" responses to SEP Q3 out of all sexual attempts recorded during the time period. Change was defined as the percentage of "yes" responses at endpoint minus percentage of "yes" responses at baseline. Change in the percentage of "yes" responses to SEP Q3 at Week 8 and Week 18 were averaged to produce an overall change in SEP Q3.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants with baseline and at least 1 SEP post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	356	354
Mean (Standard Deviation); Unit of Measure: percentage of "yes" responses
	64.53 (38.37)	63.72 (37.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.391
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; -1.58 to 4.04
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change in PAIRS Spontaneity Domain
Description	PAIRS was a self-administered, 29-item scale that assessed the broader psychological and interpersonal outcomes associated with ED and its treatment. Each question was rated on a Likert scale that ranged from 1 (strongly disagree) to 4 (strongly agree). The spontaneity domain score was the average score for Items 3, 12, 13, 16, 17, 19, 21, 22, and 28. Spontaneity domain scores ranged from 1 (strongly disagree) to 4 (strongly agree). Change was defined as endpoint minus baseline domain score. Change in PAIRS spontaneity domain at Week 8 and Week 18 were averaged to produce an overall change in PAIRS spontaneity domain score. Higher scores were indicative of greater spontaneity.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants with baseline and at least 1 PAIRS post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	355	354
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.33 (0.53)	0.20 (0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; 0.09 to 0.18
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Change in PAIRS Time Concerns Domain
Description	PAIRS was a self-administered, 29-item scale that assessed the broader psychological and interpersonal outcomes associated with ED and its treatment. Each question was rated on a Likert scale that ranged from 1 (strongly disagree) to 4 (strongly agree). The time concerns domain score was the average score for Items 1, 2, 6, 7, 8, 20, 24, and 25. Time concern domain scores ranged from 1 (strongly disagree) to 4 (strongly agree). Change was defined as endpoint minus baseline domain score. Change in PAIRS time concerns at Week 8 and Week 18 were averaged to produce an overall change in PAIRS time concerns domain score. Higher scores were indicative of more time concerns.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants with baseline and at least 1 PAIRS post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	355	354
Mean (Standard Deviation); Unit of Measure: units on a scale
	-0.28 (0.54)	-0.14 (0.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.19 to -0.09
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Change in International Index of Erectile Function (IIEF) Erectile Function Domain
Description	Self-reported erectile function over the past 4 weeks. IIEF erectile function was the sum of Q1 through Q5 and Q15 of the IIEF. Q1 through Q5 were scored 0 (low/no erectile function) to 5 (high erectile function) and Q15 was scored 1 (no/low confidence) to 5 (high confidence). IIEF erectile function domain scores ranged from 1 to 30. Change was defined as endpoint minus baseline domain score. Change in IIEF erectile function domain at Week 8 and Week 18 were averaged to produce an overall change in IIEF EF domain score. Higher scores were indicative of better erectile function.
Time Frame	Baseline, Week 8, and Week 18

Outcome Measure Data

Analysis Population Description

Randomized participants with baseline and at least 1 IIEF post-baseline measurement.

Arm/Group Title	Tadalafil	Sildenafil
Arm/Group Description:	20 milligrams (mg) tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.	100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.
Overall Number of Participants Analyzed	355	354
Mean (Standard Deviation); Unit of Measure: units on a scale
	12.03 (6.75)	11.86 (6.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tadalafil, Sildenafil
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.364
	Comments	P-Value and LS mean difference were from a crossover mixed effect model that included treatment, period, sequence, and site as fixed effects, baseline value of efficacy measure as covariate, and participant within sequence as random effect.
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.55
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Tadalafil (Treatment Periods)		Sildenafil (Treatment Periods)		Tadalafil (Extension Phase)		Sildenafil (Extension Phase)
Arm/Group Description	20 mg tadalafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.		100 mg sildenafil taken orally, as needed, for 8 weeks either during Treatment Period 1 or Treatment Period 2.		Participants who preferred tadalafil over sildenafil received 20 mg tadalafil taken orally, as needed, for an additional 8 weeks.		Participants who preferred sildenafil over tadalafil received 100 mg sildenafil taken orally, as needed, for an additional 8 weeks.
All-Cause Mortality
	Tadalafil (Treatment Periods)		Sildenafil (Treatment Periods)		Tadalafil (Extension Phase)		Sildenafil (Extension Phase)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--		--/--
Serious Adverse Events
	Tadalafil (Treatment Periods)		Sildenafil (Treatment Periods)		Tadalafil (Extension Phase)		Sildenafil (Extension Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/363 (0.00%)		0/361 (0.00%)		0/231 (0.00%)		0/106 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Tadalafil (Treatment Periods)		Sildenafil (Treatment Periods)		Tadalafil (Extension Phase)		Sildenafil (Extension Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/363 (8.26%)		26/361 (7.20%)		7/231 (3.03%)		2/106 (1.89%)
Cardiac disorders
Palpitations † 1	1/363 (0.28%)	1	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Ear and labyrinth disorders
Deafness † 1	1/363 (0.28%)	1	0/361 (0.00%)	0	0/231 (0.00%)	0	0/106 (0.00%)	0
Vertigo † 1	1/363 (0.28%)	1	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Eye disorders
Eye pain † 1	2/363 (0.55%)	2	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Eye swelling † 1	3/363 (0.83%)	3	0/361 (0.00%)	0	1/231 (0.43%)	1	0/106 (0.00%)	0
Ocular hyperaemia † 1	0/363 (0.00%)	0	2/361 (0.55%)	2	0/231 (0.00%)	0	0/106 (0.00%)	0
Vision blurred † 1	1/363 (0.28%)	1	1/361 (0.28%)	1	1/231 (0.43%)	1	0/106 (0.00%)	0
Gastrointestinal disorders
Abdominal discomfort † 1	0/363 (0.00%)	0	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Abdominal distension † 1	1/363 (0.28%)	1	0/361 (0.00%)	0	0/231 (0.00%)	0	0/106 (0.00%)	0
Diarrhoea † 1	0/363 (0.00%)	0	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Dyspepsia † 1	1/363 (0.28%)	1	2/361 (0.55%)	2	0/231 (0.00%)	0	0/106 (0.00%)	0
Gastric haemorrhage † 1	1/363 (0.28%)	1	0/361 (0.00%)	0	0/231 (0.00%)	0	0/106 (0.00%)	0
Gastrooesophageal reflux disease † 1	0/363 (0.00%)	0	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Nausea † 1	1/363 (0.28%)	1	2/361 (0.55%)	3	1/231 (0.43%)	1	0/106 (0.00%)	0
General disorders
Face oedema † 1	1/363 (0.28%)	1	1/361 (0.28%)	1	0/231 (0.00%)	0	1/106 (0.94%)	1
Feeling hot † 1	0/363 (0.00%)	0	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Pyrexia † 1	0/363 (0.00%)	0	2/361 (0.55%)	2	0/231 (0.00%)	0	0/106 (0.00%)	0
Thirst † 1	1/363 (0.28%)	1	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/363 (0.28%)	1	0/361 (0.00%)	0	0/231 (0.00%)	0	0/106 (0.00%)	0
Aspartate aminotransferase increased † 1	1/363 (0.28%)	1	0/361 (0.00%)	0	0/231 (0.00%)	0	0/106 (0.00%)	0
Body temperature increased † 1	0/363 (0.00%)	0	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Metabolism and nutrition disorders
Diabetes mellitus † 1	1/363 (0.28%)	1	1/361 (0.28%)	1	1/231 (0.43%)	1	0/106 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	2/363 (0.55%)	2	2/361 (0.55%)	2	0/231 (0.00%)	0	0/106 (0.00%)	0
Groin pain † 1	1/363 (0.28%)	2	0/361 (0.00%)	0	0/231 (0.00%)	0	0/106 (0.00%)	0
Myalgia † 1	0/363 (0.00%)	0	0/361 (0.00%)	0	1/231 (0.43%)	1	0/106 (0.00%)	0
Nervous system disorders
Dizziness † 1	6/363 (1.65%)	7	3/361 (0.83%)	3	2/231 (0.87%)	4	0/106 (0.00%)	0
Headache † 1	10/363 (2.75%)	13	5/361 (1.39%)	5	2/231 (0.87%)	4	0/106 (0.00%)	0
Psychiatric disorders
Abnormal dreams † 1	0/363 (0.00%)	0	0/361 (0.00%)	0	1/231 (0.43%)	1	0/106 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/363 (0.28%)	1	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Nasal congestion † 1	3/363 (0.83%)	4	3/361 (0.83%)	3	1/231 (0.43%)	1	0/106 (0.00%)	0
Nasal obstruction † 1	1/363 (0.28%)	1	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
Rhinorrhoea † 1	1/363 (0.28%)	1	0/361 (0.00%)	0	0/231 (0.00%)	0	0/106 (0.00%)	0
Vascular disorders
Flushing † 1	2/363 (0.55%)	2	6/361 (1.66%)	7	0/231 (0.00%)	0	1/106 (0.94%)	1
Hypertension † 1	1/363 (0.28%)	1	0/361 (0.00%)	0	0/231 (0.00%)	0	0/106 (0.00%)	0
Varicose vein † 1	0/363 (0.00%)	0	1/361 (0.28%)	1	0/231 (0.00%)	0	0/106 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01352507
• Other Study ID Numbers: 14035; H6D-CR-LVIZ ( Other Identifier: Eli Lilly and Company )
• First Submitted: May 10, 2011
• First Posted: May 12, 2011
• Results First Submitted: March 13, 2013
• Results First Posted: April 26, 2013
• Last Update Posted: April 26, 2013