COUPLE: Concomitant Use of PriLigy in Men Treated for Erectile Dysfunction

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01063855
• Collaborator: (none)
• Enrollment: 495
• Locations: 73
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of dapoxetine compared to placebo in men with premature ejaculation and erectile dysfunction who are currently being treated with a phosphodiesterase-5 inhibitor (ie, sildenafil, vardenafil, or tadalafil) for erectile dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Erectile Dysfunction; Sexual Dysfunction	Drug: Placebo; Drug: Dapoxetine; Drug: PDE5I (phosphodiesterase-5 inhibitor)	Phase 3

Detailed Description

Premature ejaculation (PE) and erectile dysfunction (ED) are forms of sexual dysfunction in men. An objective measurement of PE in clinical studies is the intravaginal ejaculatory latency time (IELT), which is the time it takes for a man to ejaculate during sexual intercourse (as measured by stopwatch). This is a multicenter, double-blind (neither the physician or the study participant will know the identity of the treatment assigned), randomized (study drug assigned by chance) efficacy and safety study of dapoxetine compared with placebo (a sugar pill) in men with premature ejaculation who are currently being treated for ED with a phosphodiesterase 5 (PDE-5) inhibitor such as sildenafil, vardenafil, or tadalafil. A maximum of 656 men 18 years or older (hereafter referred to as study participants) who have received treatment with a PDE-5 inhibitor for at least 3 months prior to study entry will be enrolled. The study will last approximately 18 weeks and includes a 4-week screening period, a 12-week treatment period, and a follow-up telephone contact approximately 2 weeks after the end of treatment. Both the study participant and his partner will be required to attend the screening visit and to sign an informed consent form documenting that they understand and agree to the requirements for the study. After initial screening procedures are completed, study participants who qualify for the study will enter a 4-week screening period. During the 4 weeks, the study participant and his partner will be provided with a stopwatch to time and record the IELT during all attempts at sexual intercourse. At the next scheduled clinic visit which is Day 1 of the double-blind treatment period, study participants who continue to qualify for the study will be assigned by chance (like flipping a coin) to receive 1 of 2 study treatments (dapoxetine or placebo) for 12 weeks in addition to prescribed treatment with a PDE-5 inhibitor. Study participants will be instructed to take study drug with or without food with at least 1 full glass of water approximately 1 to 3 hours before sexual activity (no more than 1 dose should be taken within a 24-hour period). During the 12-week treatment period, the study participant and his partner will be asked to time and record the IELT during all attempts at sexual intercourse on Treatment Event Logs provided. Study participants will return to the clinic after 4, 8 and 12 weeks of treatment for routine safety assessments (including review of Treatment Event Logs returned) and to be dispensed study drug. Following 12 weeks of treatment (or at the time of early withdrawal from the study) end-of-treatment safety and efficacy evaluations will be performed at the final clinic visit. Approximately 2 weeks later, a follow up telephone call will be made to the study participant to collect information on any adverse events that may have occurred or concomitant therapy received since the time of the last clinic visit. The primary outcome measure in the study is the average IELT, as measured by stopwatch, during sexual intercourse at the end of the treatment period (Week 12). Safety will be monitored during the study by evaluating adverse events, physical examination findings, results from clinical laboratory tests, and concomitant medication usage. An Independent Data Monitoring Committee (IDMC) will be established to monitor the safety and efficacy of study participants during the study. In addition, an interim (preliminary) analysis will be performed during the study to monitor safety and efficacy after approximately 268 men have completed 12 weeks of treatment (also includes any study participants who did not complete treatment and were withdrawn early from the study). Study participants will receive either dapoxetine or matching placebo tablets at a dose of 30 mg prn (as needed) taken orally (by mouth) with or without food with at least 1 full glass of water approximately 1 to 3 hours before sexual activity (not to be taken more than once every 24 hours). At Weeks 4 or 8, the dose of dapoxetine or matching placebo may be increased to a maximum of 60 mg prn if specific predefined criteria are met or be subsequently decreased from 60 to 30 mg at Weeks 4 or 8.

Study Design

• Study Type: Interventional
• Actual Enrollment: 495 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of the Efficacy and Safety of Dapoxetine in Men With Premature Ejaculation and Concomitant Erectile Dysfunction Treated With a Phosphodiesterase-5 Inhibitor
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dapoxetine + PDE5I Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + a PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Drug: Dapoxetine; 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks.; Drug: PDE5I (phosphodiesterase-5 inhibitor); Patients were to be using a stable regimen of a PDE5-I (i.e., sildenafil, vardenafil, or tadalafil), as reported by the patient for the treatment of erectile dysfunction (ED) for at least 3 months before screening and up to 12 weeks during treatment in the study.
Placebo Comparator: Placebo + PDE5I Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + a PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Drug: Placebo; Tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks.; Drug: PDE5I (phosphodiesterase-5 inhibitor); Patients were to be using a stable regimen of a PDE5-I (i.e., sildenafil, vardenafil, or tadalafil), as reported by the patient for the treatment of erectile dysfunction (ED) for at least 3 months before screening and up to 12 weeks during treatment in the study.

Outcome Measures

Primary Outcome Measures

1. The Average Intravaginal Ejaculatory Latency Time (IELT) at Week 12 [Baseline, Week 12]

   The intravaginal ejaculatory latency time (IELT) is the time it takes for a man to ejaculate during sexual intercourse (as measured by stopwatch). The data below show the average IELT measured in minutes at Baseline (before treatment) to Endpoint (after 12 weeks of treatment). In this study, patients took placebo or dapoxetine along with a stable dose of a phosphodiesterase-5 inhibitor (PDE5I) prescribed prior to study entry for the treatment of erectile dysfunction.

Secondary Outcome Measures

1. The Percentage of Patients Reporting At Least a 2-category Increase in Control Over Ejaculation [At the end of treatment (Week 12)]

   The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's control over ejaculation on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who reported at least a 2-category increase in control over ejaculation is provided in the table below.

2. The Percentage of Patients Who Achieved 1-category or Greater Decrease (Improvement) in Personal Distress Related to Ejaculation [At Endpoint (After 12 weeks of treatment)]

   The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of distress related to the speed of ejaculation on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who achieved 1-category or greater decrease (improvement) in personal distress related to the speed of ejaculation is provided in the table below.

3. The Percentage of Patients Reporting a Composite Score of At Least a 2-category Increase in Control Over Ejaculation and At Least a 1-category Decrease in Personal Distress [At the end of treatment (Week 12)]

   The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of distress related to the speed of ejaculation and control over ejaculation on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who reported a composite score of at least a 2-category increase in control over ejaculation and at least a 1-category decrease (improvement) in personal distress is provided in the table below.

4. The Percentage of Patients Who Achieved a 1-category or Greater Increase in Satisfaction With Sexual Intercourse [Endpoint (After 12 weeks of treatment)]

   The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of satisfaction with intercourse on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who achieved 1-category or greater increase in satisfaction with sexual intercourse is provided in the table below.

5. The Percentage of Patients Reporting At Least a "Better" Response to Treatment [Endpoint (After 12 weeks of treatment)]

   The "Clinical Global Impression of Change" (CGIC) was used to assess the degree of improvement the patient experienced with premature ejaculation (PE) since initiating treatment with study drug on a 7-point scale from "Much worse, Worse, Slightly worse, No change, Slightly better, Better, to Much better". The percentage of patients who reported improvement in PE of at least "better" at Endpoint (after 12 weeks of treatment) is provided in the table below.

6. The Percentage of Patients Who Reported At Least a 1-category Decrease (Improvement) in Interpersonal Difficulty Related to Ejaculation [Endpoint (After 12 weeks of treatment)]

   The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of interpersonal difficulty related to ejaculation on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who reported at least a 1-category decrease (improvement) in interpersonal difficulty related to ejaculation is provided in the table below.

7. The Percentage of Patients Reporting At Least a "Slightly Better" Response to Treatment [Endpoint (After 12 weeks of treatment)]

   The "Clinical Global Impression of Change" (CGIC) was used to assess the degree of improvement the patient experienced with premature ejaculation (PE) since initiating treatment with study drug on a 7-point scale from "Much worse, Worse, Slightly worse, No change, Slightly better, Better, to Much better". The percentage of patients who reported improvement in PE of at least "slightly better" at Endpoint (after 12 weeks of treatment) is provided in the table below.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Clinical diagnosis of erectile dysfunction (ED), International Index of Erectile Function (IIEF) score >=21 at screening and baseline, and receiving treatment with a stable regimen of a phosphodiesterase 5 (PDE 5) inhibitor (ie, sildenafil, vardenafil, or tadalafil) for the treatment of ED for at least 3 months before screening

• Study participant in a stable, monogamous sexual relationship with the same woman for at least 6 months before screening and plan to maintain this relationship for the duration of the study

• Study participant medically stable (ie, in good general health) on the basis of physical examination, medical history, vital signs, 12 lead ECG, and clinical laboratory tests performed at screening

Exclusion Criteria:

• History suggestive of syncope (a condition characterized by a loss of consciousness)

• History of medical events such as surgical interventions or neurologic conditions (eg, multiple sclerosis), trauma, or infections that are associated with the development of symptoms of premature ejaculation (PE) and considered a potential cause of PE

• Current major psychiatric disorder such as mood disorder, anxiety disorder, schizophrenia, mania, suicidal ideation, other psychotic disorder, or alcoholism

• Known allergy, hypersensitivity, or intolerance to selective serotonin reuptake inhibitors (SSRIs) or selective noradrenaline reuptake inhibitors (SNRIs)

• Taken another investigational drug (or vaccine) within 30 days or used an investigational medical device within 6 months before screening, or enrolled in another investigational study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Decatur	Alabama	United States
2		Huntsville	Alabama	United States
3		Englewood	Colorado	United States
4		Aventura	Florida	United States
5		Clearwater	Florida	United States
6		Gainesville	Florida	United States
7		West Palm Beach	Florida	United States
8		Evansville	Indiana	United States
9		Fort Wayne	Indiana	United States
10		Baltimore	Maryland	United States
11		Olive Branch	Mississippi	United States
12		Kansas City	Missouri	United States
13		Poughkeepsie	New York	United States
14		Raleigh	North Carolina	United States
15		Cleveland	Ohio	United States
16		Portland	Oregon	United States
17		Salem	Oregon	United States
18		Ettrick	Virginia	United States
19		Middleton	Wisconsin	United States
20		Buenos Aires		Argentina
21		Ciudad Autonoma De		Argentina
22		Malvern		Australia
23		Maroubra		Australia
24		Perth		Australia
25		St Leonards		Australia
26		Brussel		Belgium
27		Bruxelles		Belgium
28		Edegem		Belgium
29		Liège		Belgium
30		Coquitlam	British Columbia	Canada
31		Guelph	Ontario	Canada
32		Newmarket	Ontario	Canada
33		Oakville	Ontario	Canada
34		Sarnia	Ontario	Canada
35		Toronto	Ontario	Canada
36		Montreal	Quebec	Canada
37		Pointe-Claire	Quebec	Canada
38		Garches		France
39		Lille		France
40		Lyon Cedex 03		France
41		Lyon		France
42		Marseille		France
43		Nimes Cedex 9		France
44		Paris		France
45		Toulouse		France
46		Chunjoo		Korea, Republic of
47		Kwangjoo		Korea, Republic of
48		Pusan		Korea, Republic of
49		Seoul		Korea, Republic of
50		Kuala Lumpur N/A		Malaysia
51		Kuala Lumpur		Malaysia
52		Kuching		Malaysia
53		Petaling Jaya		Malaysia
54		Cd. De Mexico		Mexico
55		Culiacan		Mexico
56		Durango		Mexico
57		Monterrey		Mexico
58		Katowice		Poland
59		Lodz		Poland
60		Lublin		Poland
61		Szcezecin		Poland
62		Wroclaw		Poland
63		Moscow		Russian Federation
64		St Peterburg		Russian Federation
65		St Petersburg		Russian Federation
66		St. Petersburg		Russian Federation
67		Kaohsiung		Taiwan
68		Tao-Yuan		Taiwan
69		Chipping Norton		United Kingdom
70		Leeds Yorkshire		United Kingdom
71		Lichfield		United Kingdom
72		Reading		United Kingdom
73		South Brent		United Kingdom

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT01063855
• Other Study ID Numbers: CR016486; R096769PRE3008; 2009-013616-12
• First Posted: Feb 5, 2010
• Last Update Posted: Jan 24, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Erectile Dysfunction; Sexual Dysfunction; Dapoxetine hydrochloride; PRILIGY; Premature ejaculation; Serotonin Uptake Inhibitors; Sildenafil (Viagra); Vardenafil (Levitra); Tadalafil (Cialis)
• Additional relevant MeSH terms: Erectile Dysfunction; Premature Ejaculation; Phosphodiesterase 5 Inhibitors

Study Results

Participant Flow

Recruitment Details	Study R096769-PRE-3008 was conducted at 69 study centers in 13 countries between 27 April 2010 and 31 August 2011.
Pre-assignment Detail	Of the 495 randomized patients, 429 patients completed the study, and 66 patients were discontinued from the study. All randomized patients (N=495) were included in the intent-to-treat analysis set of patients for efficacy and safety.

Arm/Group Title	PDE5I + PLACEBO	PDE5I + DPX
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
Period Title: Overall Study
STARTED	245	250
COMPLETED	208	221
NOT COMPLETED	37	29

Baseline Characteristics

Arm/Group Title	PDE5I + PLACEBO	PDE5I + DPX	Total
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Total of all reporting groups
Overall Participants	245	250	495
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	228 93.1%	231 92.4%	459 92.7%
>=65 years	17 6.9%	19 7.6%	36 7.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.9 (11.96)	49.5 (11.23)	48.7 (11.61)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	245 100%	250 100%	495 100%
Baseline BMI (kg/cm2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/cm2]	27.2 (4.50)	27.1 (4.55)	27.2 (4.52)

Outcome Measures

1. Primary Outcome

Title	The Average Intravaginal Ejaculatory Latency Time (IELT) at Week 12
Description	The intravaginal ejaculatory latency time (IELT) is the time it takes for a man to ejaculate during sexual intercourse (as measured by stopwatch). The data below show the average IELT measured in minutes at Baseline (before treatment) to Endpoint (after 12 weeks of treatment). In this study, patients took placebo or dapoxetine along with a stable dose of a phosphodiesterase-5 inhibitor (PDE5I) prescribed prior to study entry for the treatment of erectile dysfunction.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized patients. Missing efficacy data at Week 12 was imputed based on the last postbaseline observation carried forward (LPOCF) method.

Arm/Group Title	PDE5I + Placebo (Baseline)	PDE5I + Placebo (Week 12)	PDE5I + Dapoxetine (Baseline)	PDE5I + Dapoxetine (Week 12)
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction
Measure Participants	241	230	249	240
Mean (Standard Deviation) [minutes]	1.1 (0.53)	3.4 (3.54)	1.1 (0.55)	5.2 (5.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PDE5I + Placebo (Baseline), PDE5I + Placebo (Week 12), PDE5I + Dapoxetine (Baseline), PDE5I + Dapoxetine (Week 12)
	Comments	Null Hypothesis: No difference at Week 12 last postbaseline observations carried forward (LPOCF) Alternative Hypothesis:- Difference at Week 12 LPOCF >0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	To properly adjust for multiplicity, a hierarchical (step-down) testing procedure with a priori ordered hypothesis was used to control the family-wise type I error was rate.
	Method	ANCOVA
	Comments	ANCOVA model included treatment, PDE5I stratum, baseline Average IELT stratum, and region, as cofactors and baseline Average IELT as a covariate.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	1.69
	Confidence Interval	(2-Sided) 95%; 0.837 to 2.542
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.430
	Estimation Comments	Estimates are based on two-stage sequential analysis using information fraction based weighted test statistics for PDE5I + Dapoxetine arm minus PDE5I + Placebo arm difference.

2. Secondary Outcome

Title	The Percentage of Patients Reporting At Least a 2-category Increase in Control Over Ejaculation
Description	The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's control over ejaculation on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who reported at least a 2-category increase in control over ejaculation is provided in the table below.
Time Frame	At the end of treatment (Week 12)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized patients. Missing efficacy data at Week 12 was imputed based on the last postbaseline observation carried forward (LPOCF) method.

Arm/Group Title	PDE5I + Placebo	PDE5I + Dapoxetine
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
Measure Participants	229	246
Number [Percentage of Patients]	32.3	45.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PDE5I + Placebo (Baseline), PDE5I + Placebo (Week 12)
	Comments	Null hypothesis: No difference at Week 12 last postbaseline observation carried forward (LPOCF). Alternative hypothesis: Difference at Week 12 LPOCF > 0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	A hierarchical (step-down) testing procedure with a priori ordered hypothesis was used to control the family-wise type 1 error rate.
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel (CMH) test, controlling for type of PDE5I stratum, baseline average IELT stratum, and region.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	13.6
	Confidence Interval	(2-Sided) 95%; 4.9 to 22.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk Difference (RD) = PDE5I + Dapoxetine arm - PDE5I + placebo arm.

3. Secondary Outcome

Title	The Percentage of Patients Who Achieved 1-category or Greater Decrease (Improvement) in Personal Distress Related to Ejaculation
Description	The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of distress related to the speed of ejaculation on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who achieved 1-category or greater decrease (improvement) in personal distress related to the speed of ejaculation is provided in the table below.
Time Frame	At Endpoint (After 12 weeks of treatment)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized patients. Missing efficacy data at Week 12 was imputed based on the last postbaseline observation carried forward (LPOCF) method.

Arm/Group Title	PDE5I + Placebo	PDE5I + Dapoxetine
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
Measure Participants	229	246
Number [Percentage of Patients]	67.2	76.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PDE5I + Placebo (Baseline), PDE5I + Placebo (Week 12)
	Comments	Null Hypothesis: No difference at Week 12 last postbaseline observation carried forward (LPOCF).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	A hierarchical (step-down) testing procedure with a priori ordered hypothesis was used to control the family-wise type 1 error rate.
	Method	Cochran-Mantel-Haenszel
	Comments	The Cochran-Mantel-Haenszel (CMH) test, controlling for type of PDE5I stratum, baseline average IELT stratum, and region.
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	9.2
	Confidence Interval	(2-Sided) 95%; 1.1 to 17.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk Difference (RD) = PDE5I + Dapoxetine arm - PDE5I + Placebo arm.

4. Secondary Outcome

Title	The Percentage of Patients Reporting a Composite Score of At Least a 2-category Increase in Control Over Ejaculation and At Least a 1-category Decrease in Personal Distress
Description	The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of distress related to the speed of ejaculation and control over ejaculation on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who reported a composite score of at least a 2-category increase in control over ejaculation and at least a 1-category decrease (improvement) in personal distress is provided in the table below.
Time Frame	At the end of treatment (Week 12)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized patients. Missing efficacy data at Week 12 was imputed based on the last postbaseline observation carried forward (LPOCF) method.

Arm/Group Title	PDE5I + Placebo	PDE5I + Dapoxetine
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
Measure Participants	229	246
Number [Percentage of Patients]	30.6	43.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PDE5I + Placebo (Baseline), PDE5I + Placebo (Week 12)
	Comments	Null Hypothesis: No difference at Week 12 last postbaseline observation carried forward (LPOCF) Alternative Hypothesis: PDE5I + Dapoxetine is superior to PDE5I + Placebo with respect to the outcome measure at Week 12 LPOCF.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	To properly adjust for multiplicity, a hierarchical (step-down) testing procedure with a priori ordered hypothesis was used to control the family-wise type I error.
	Method	Regression, Logistic
	Comments	Logistic Regression model included treatment, type of PDE5i stratum, baseline Average IELT stratum, and region, as factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.78
	Confidence Interval	(2-Sided) 95%; 1.204 to 2.619
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimates are based on two-stage sequential analysis using information fraction based weighted test statistics for PDE5I + Dapoxetine arm over PDE5I + Placebo arm ratio.

5. Secondary Outcome

Title	The Percentage of Patients Who Achieved a 1-category or Greater Increase in Satisfaction With Sexual Intercourse
Description	The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of satisfaction with intercourse on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who achieved 1-category or greater increase in satisfaction with sexual intercourse is provided in the table below.
Time Frame	Endpoint (After 12 weeks of treatment)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized patients. Missing efficacy data at Week 12 was imputed based on the last postbaseline observation carried forward (LPOCF) method.

Arm/Group Title	PDE5I + Placebo	PDE5I + Dapoxetine
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
Measure Participants	229	246
Number [Percentage of Patients]	55.0	66.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PDE5I + Placebo (Baseline), PDE5I + Placebo (Week 12)
	Comments	Null Hypothesis: No difference at Week 12 last postbaseline observation carrried forward (LPOCF) Alternative Hypothesis:- PDE5I + Dapoxetine is superior to PDE5I + Placebo with respect to the outcome measure at Week 12 LPOCF.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments	To properly adjust for multiplicity, a hierarchical (step-down) testing procedure with a priori ordered hypothesis was used to control the family-wise type I error was rate.
	Method	Regression, Logistic
	Comments	Logistic Regression model included treatment, type of PDE5i stratum, baseline Average IELT stratum, and region, as factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.63
	Confidence Interval	(2-Sided) 95%; 1.108 to 2.394
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimates are based on two-stage sequential analysis using information fraction based weighted test statistics for PDE5I + Dapoxetine arm over PDE5I + Placebo arm ratio.

6. Secondary Outcome

Title	The Percentage of Patients Reporting At Least a "Better" Response to Treatment
Description	The "Clinical Global Impression of Change" (CGIC) was used to assess the degree of improvement the patient experienced with premature ejaculation (PE) since initiating treatment with study drug on a 7-point scale from "Much worse, Worse, Slightly worse, No change, Slightly better, Better, to Much better". The percentage of patients who reported improvement in PE of at least "better" at Endpoint (after 12 weeks of treatment) is provided in the table below.
Time Frame	Endpoint (After 12 weeks of treatment)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized patients. Missing efficacy data at Week 12 was imputed based on the last postbaseline observation carried forward (LPOCF) method.

Arm/Group Title	PDE5I + Placebo	PDE5I + Dapoxetine
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
Measure Participants	229	246
Number [Percentage of Patients]	35.4	56.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PDE5I + Placebo (Baseline), PDE5I + Placebo (Week 12)
	Comments	Null Hypothesis: No difference at Week 12 last postbaseline observation carried forward (LPOCF) Alternative Hypothesis:- PDE5I + Dapoxetine is superior to PDE5I + Placebo with respect to the outcome measure at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	To properly adjust for multiplicity, a hierarchical (step-down) testing procedure with a priori ordered hypothesis was used to control the family-wise type I error was rate
	Method	Regression, Logistic
	Comments	Logistic Regression model included treatment, type of PDE5i stratum, baseline Average IELT stratum, and region, as factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.42
	Confidence Interval	(2-Sided) 95%; 1.642 to 3.568
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimates are based on two-stage sequential analysis using information fraction based weighted test statistics for PDE5I + Dapoxetine arm over PDE5I + Placebo arm ratio.

7. Secondary Outcome

Title	The Percentage of Patients Who Reported At Least a 1-category Decrease (Improvement) in Interpersonal Difficulty Related to Ejaculation
Description	The Premature Ejaculation Profile (PEP), a patient-reported outcome measure was used to rate the patient's level of interpersonal difficulty related to ejaculation on a 5-point scale from "Very poor, Poor, Fair, Good, to Very Good." The percentage of patients who reported at least a 1-category decrease (improvement) in interpersonal difficulty related to ejaculation is provided in the table below.
Time Frame	Endpoint (After 12 weeks of treatment)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized patients. Missing efficacy data at Week 12 was imputed based on the last postbaseline observation carried forward (LPOCF) method.

Arm/Group Title	PDE5I + Placebo	PDE5I + Dapoxetine
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
Measure Participants	229	246
Number [Percentage of Patients]	61.6	67.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PDE5I + Placebo (Baseline), PDE5I + Placebo (Week 12)
	Comments	Null Hypothesis: No difference at Week 12 last postbaseline observation carried forward (LPOCF) Alternative Hypothesis:- PDE5I + Dapoxetine is superior to PDE5I + Placebo with respect to the outcome measure at Week 12 LPOCF.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	To properly adjust for multiplicity, a hierarchical (step-down) testing procedure with a priori ordered hypothesis was used to control the family-wise type I error was rate.
	Method	Regression, Logistic
	Comments	Logistic Regression model included treatment, type of PDE5i stratum, baseline Average IELT stratum, and region, as factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 0.897 to 1.965
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimates are based on two-stage sequential analysis using information fraction based weighted test statistics for PDE5I + Dapoxetine arm over PDE5I + Placebo arm ratio.

8. Secondary Outcome

Title	The Percentage of Patients Reporting At Least a "Slightly Better" Response to Treatment
Description	The "Clinical Global Impression of Change" (CGIC) was used to assess the degree of improvement the patient experienced with premature ejaculation (PE) since initiating treatment with study drug on a 7-point scale from "Much worse, Worse, Slightly worse, No change, Slightly better, Better, to Much better". The percentage of patients who reported improvement in PE of at least "slightly better" at Endpoint (after 12 weeks of treatment) is provided in the table below.
Time Frame	Endpoint (After 12 weeks of treatment)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all randomized patients. Missing efficacy data at Week 12 was imputed based on the last postbaseline observation carried forward (LPOCF) method.

Arm/Group Title	PDE5I + Placebo	PDE5I + Dapoxetine
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.	Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
Measure Participants	230	240
Number [Percentage of Patients]	66.9	91.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PDE5I + Placebo (Baseline), PDE5I + Placebo (Week 12)
	Comments	Null Hypothesis: No difference at Week 12 last postbaseline observation carried forward (LPOCF) Alternative Hypothesis:- PDE5I + Dapoxetine is superior to PDE5I + Placebo with respect to the outcome measure at Week 12.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	To properly adjust for multiplicity, a hierarchical (step-down) testing procedure with a priori ordered hypothesis was used to control the family-wise type I error was rate.
	Method	Regression, Logistic
	Comments	Logistic Regression model included treatment, type of PDE5i stratum, baseline Average IELT stratum, and region, as factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.21
	Confidence Interval	(2-Sided) 95%; 1.425 to 3.423
	Parameter Dispersion	Type: Value:
	Estimation Comments	Estimates are based on two-stage sequential analysis using information fraction based weighted test statistics for PDE5I + Dapoxetine arm over PDE5I + Placebo arm ratio.

Adverse Events

Time Frame	Adverse events were reported for the duration of the study; each patient participated in the study for approximately 18 weeks.
Arm/Group Title	PDE5I + PLACEBO		PDE5I + DPX
Arm/Group Description	Placebo tablets identical in appearance to dapoxetine taken 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.		Dapoxetine 30 mg to 60 mg tablets 1 to 3 hours before sexual activity prn (as needed) not to be taken more than once every 24 hours for 12 weeks + PDE5I (phosphodiesterase-5 inhibitor) prescribed prior to study entry for the treatment of erectile dysfunction.
All Cause Mortality
	PDE5I + PLACEBO		PDE5I + DPX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PDE5I + PLACEBO		PDE5I + DPX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/245 (1.6%)		3/250 (1.2%)
Blood and lymphatic system disorders
Anaemia	0/245 (0%)		1/250 (0.4%)
Cardiac disorders
Myocardial Infarction	0/245 (0%)		1/250 (0.4%)
Musculoskeletal and connective tissue disorders
Juvenile Arthritis	1/245 (0.4%)		0/250 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma	1/245 (0.4%)		0/250 (0%)
Renal Cell Carcinoma	1/245 (0.4%)		0/250 (0%)
Nervous system disorders
Syncope	0/245 (0%)		1/250 (0.4%)
Renal and urinary disorders
Renal Colic	0/245 (0%)		1/250 (0.4%)
Social circumstances
Miscarriage of Partner	1/245 (0.4%)		0/250 (0%)
Other (Not Including Serious) Adverse Events
	PDE5I + PLACEBO		PDE5I + DPX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/245 (18.4%)		73/250 (29.2%)
Cardiac disorders
Palpitations	0/245 (0%)		1/250 (0.4%)
Congenital, familial and genetic disorders
Phimosis	1/245 (0.4%)		0/250 (0%)
Ear and labyrinth disorders
Tinnitus	1/245 (0.4%)		1/250 (0.4%)
Vertigo	1/245 (0.4%)		4/250 (1.6%)
Vertigo Positional	1/245 (0.4%)		0/250 (0%)
Eye disorders
Eye Pain	0/245 (0%)		1/250 (0.4%)
Eyelid Ptosis	0/245 (0%)		1/250 (0.4%)
Vision Blurred	0/245 (0%)		1/250 (0.4%)
Gastrointestinal disorders
Abdominal Pain	1/245 (0.4%)		0/250 (0%)
Abdominal Pain Upper	1/245 (0.4%)		0/250 (0%)
Diarrhoea	2/245 (0.8%)		9/250 (3.6%)
Dry Mouth	0/245 (0%)		1/250 (0.4%)
Dyspepsia	1/245 (0.4%)		3/250 (1.2%)
Flatulence	0/245 (0%)		1/250 (0.4%)
Gastritis	1/245 (0.4%)		1/250 (0.4%)
Gastrooesophageal Reflux Disease	1/245 (0.4%)		0/250 (0%)
Inguinal Hernia	0/245 (0%)		1/250 (0.4%)
Nausea	3/245 (1.2%)		23/250 (9.2%)
Toothache	0/245 (0%)		2/250 (0.8%)
Vomiting	1/245 (0.4%)		1/250 (0.4%)
General disorders
Adverse Drug Reaction	1/245 (0.4%)		0/250 (0%)
Asthenia	0/245 (0%)		1/250 (0.4%)
Chills	0/245 (0%)		1/250 (0.4%)
Fatigue	1/245 (0.4%)		2/250 (0.8%)
Irritability	0/245 (0%)		1/250 (0.4%)
Hepatobiliary disorders
Cholelithiasis	1/245 (0.4%)		0/250 (0%)
Infections and infestations
Bacterial Food Poisoning	0/245 (0%)		1/250 (0.4%)
Ear Infection Viral	1/245 (0.4%)		0/250 (0%)
Gastroenteritis	1/245 (0.4%)		1/250 (0.4%)
Influenza	1/245 (0.4%)		2/250 (0.8%)
Lower Respiratory Tract Infection	0/245 (0%)		1/250 (0.4%)
Nasopharyngitis	4/245 (1.6%)		3/250 (1.2%)
Oral Herpes	1/245 (0.4%)		0/250 (0%)
Pharyngitis	1/245 (0.4%)		2/250 (0.8%)
Respiratory Tract Infection Viral	1/245 (0.4%)		0/250 (0%)
Upper Respiratory Tract Infection	1/245 (0.4%)		4/250 (1.6%)
Injury, poisoning and procedural complications
Arthropod Bite	0/245 (0%)		1/250 (0.4%)
Back Injury	0/245 (0%)		1/250 (0.4%)
Contusion	0/245 (0%)		1/250 (0.4%)
Hand Fracture	1/245 (0.4%)		0/250 (0%)
Joint Injury	0/245 (0%)		1/250 (0.4%)
Joint Sprain	1/245 (0.4%)		0/250 (0%)
Meniscus Lesion	0/245 (0%)		1/250 (0.4%)
Procedural Pain	1/245 (0.4%)		0/250 (0%)
Road Traffic Accident	1/245 (0.4%)		0/250 (0%)
Tendon Rupture	1/245 (0.4%)		0/250 (0%)
Thermal Burn	1/245 (0.4%)		0/250 (0%)
Tooth Fracture	1/245 (0.4%)		0/250 (0%)
Investigations
Blood Pressure Increased	0/245 (0%)		1/250 (0.4%)
Gastric Ph Decreased	1/245 (0.4%)		0/250 (0%)
Metabolism and nutrition disorders
Decreased Appetite	0/245 (0%)		1/250 (0.4%)
Hypertriglyceridaemia	0/245 (0%)		1/250 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/245 (0.4%)		1/250 (0.4%)
Back Pain	2/245 (0.8%)		1/250 (0.4%)
Musculoskeletal Chest Pain	1/245 (0.4%)		0/250 (0%)
Musculoskeletal Pain	2/245 (0.8%)		0/250 (0%)
Musculoskeletal Stiffness	1/245 (0.4%)		0/250 (0%)
Myalgia	1/245 (0.4%)		0/250 (0%)
Neck Pain	1/245 (0.4%)		0/250 (0%)
Nervous system disorders
Disturbance in Attention	0/245 (0%)		1/250 (0.4%)
Dizziness	2/245 (0.8%)		6/250 (2.4%)
Dizziness Exertional	1/245 (0.4%)		0/250 (0%)
Dizziness Postural	1/245 (0.4%)		6/250 (2.4%)
Headache	12/245 (4.9%)		11/250 (4.4%)
Lethargy	0/245 (0%)		1/250 (0.4%)
Sedation	0/245 (0%)		1/250 (0.4%)
Somnolence	1/245 (0.4%)		0/250 (0%)
Syncope	0/245 (0%)		1/250 (0.4%)
Psychiatric disorders
Agitation	0/245 (0%)		1/250 (0.4%)
Anxiety	0/245 (0%)		1/250 (0.4%)
Euphoric Mood	0/245 (0%)		1/250 (0.4%)
Insomnia	1/245 (0.4%)		3/250 (1.2%)
Renal and urinary disorders
Haematuria	1/245 (0.4%)		0/250 (0%)
Micturition Urgency	1/245 (0.4%)		0/250 (0%)
Nephrolithiasis	1/245 (0.4%)		0/250 (0%)
Nocturia	1/245 (0.4%)		0/250 (0%)
Pollakiuria	1/245 (0.4%)		0/250 (0%)
Renal Cyst	1/245 (0.4%)		0/250 (0%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	0/245 (0%)		1/250 (0.4%)
Erectile Dysfunction	1/245 (0.4%)		0/250 (0%)
Penis Disorder	1/245 (0.4%)		0/250 (0%)
Prostatomegaly	1/245 (0.4%)		0/250 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	0/245 (0%)		1/250 (0.4%)
Hiccups	1/245 (0.4%)		0/250 (0%)
Nasal Congestion	3/245 (1.2%)		0/250 (0%)
Oropharyngeal Pain	0/245 (0%)		1/250 (0.4%)
Skin and subcutaneous tissue disorders
Erythema	0/245 (0%)		1/250 (0.4%)
Hyperhidrosis	0/245 (0%)		3/250 (1.2%)
Photosensitivity Reaction	1/245 (0.4%)		0/250 (0%)
Pruritus	0/245 (0%)		1/250 (0.4%)
Pruritus Generalised	1/245 (0.4%)		0/250 (0%)
Skin Lesion	0/245 (0%)		1/250 (0.4%)
Vascular disorders
Flushing	3/245 (1.2%)		0/250 (0%)
Hypertension	0/245 (0%)		1/250 (0.4%)

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.