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

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate whether, after two 8-week treatment periods, male patients with erectile dysfunction (ED) in China prefer 20 milligram (mg) tadalafil or 100 mg sildenafil. This trial consists of two treatment periods of 8 weeks each and an extension phase of 8 weeks, for a total of 24 weeks.

Official Title
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An Evaluation of Tadalafil and Sildenafil Treatment in Men With Erectile Dysfunction in China

Conditions
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Erectile Dysfunction

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Sildenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study Subjects Are able to read, understand and provide signed informed consent. Have a history ED of any etiological classification (psychogenic, organic, or mixed) and any severity for at least 3 months. Have never taken any phosphodiesterase 5 (PDE5) inhibitor for the treatment of ED. Anticipate having the same female sexual partner during the study for recording responses to efficacy questionnaires. If a qualifying participant has more than one female partner during the study, the participant will not be excluded from the trial. However, the participant will be required to respond to the questionnaires based on his sexual interactions with only one of these partners. Make at least 4 sexual intercourse attempts, with the female sexual study partner, during the 4-week run-in period and during the final 4 weeks of each 8-week treatment period. Not use any ED treatment including the use of herbal therapy and traditional Chinese medicine (TCM) for the treatment of ED other than study medication at any time during the study and for 96 hours after study completion. Partners Are female, at least 18 years of age at screening and will have the same male study subject as her sexual partner during the study. Are able to read, understand and provide signed informed consent. Agree to make at least 4 sexual intercourse attempts with the male sexual study partner during the 4-week run-in phase and during the final 4 weeks of each 8-week treatment period. Willing to participate in recording responses to efficacy questionnaires, sexual quality of life questionnaires and other instruments used in this study. Exclusion Criteria: Present with ED caused by other primary sexual disorders including premature ejaculation or ED caused by untreated endocrine disease. Have a history of radical prostatectomy, or other pelvic surgery with subsequent failure to achieve erection. Have a history of penile implant. Have a clinically significant penile deformity in the opinion of the investigator. Exhibit evidence of clinically significant renal insufficiency as determined by the investigator, or defined as receiving renal dialysis or having an estimated creatinine clearance of less than (<)30 milliliters per minute (mL/minute) at screening, as calculated by the local laboratory using the Cockcroft-Gault formula. Exhibit evidence of active symptomatic hepatobiliary disease at Visit 1. Exhibit Hemoglobin A1c greater than (>) 11 percent (%) at screening, in patients with a history of diabetes mellitus of any type. Present with chronic stable angina treated with long-acting nitrates, or with chronic stable angina requiring short-acting nitrates in the last 90 days, or with angina occurring during sexual intercourse in the last 6 months. Have met the criteria for unstable angina within 6 months before screening, or have a history of myocardial infarction or coronary artery bypass graft surgery within 90 days before screening, or percutaneous coronary intervention within 90 days before screening. Have any supraventricular arrhythmia with an uncontrolled ventricular response (mean heart rate >100 bpm) at rest, or have any history of spontaneous or induced sustained ventricular tachycardia (heart rate >100 beats per minute (bpm) for greater than or equal [≥] to 30 seconds) despite medical or device therapy, or use an internal cardioverter-defibrillator. Have a history of sudden cardiac arrest despite medical or device therapy. Exhibit any evidence of congestive heart failure within 6 months before screening. Have had a new or significant cardiac conduction defect within 90 days before screening. Exhibit systolic blood pressure >170 or <90 milliliters of mercury (mm Hg) or diastolic blood pressure >100 or <50 mm Hg at screening, or have a history of malignant hypertension. Have retinitis pigmentosa. Have a history of significant central nervous system injuries (including stroke and spinal cord injury) within the last 6 months. Have a history of human immunodeficiency virus (HIV) infection. Have a condition that in the opinion of the investigator would interfere with the patient's ability to provide informed consent or comply with study instructions, would place the patient at increased risk, or might confound the interpretation of study results. Currently receive treatment with nitrates, alpha [1]-adrenergic blockers (such as doxazosin), cancer chemotherapy, or antiandrogens (except finasteride taken as Propecia™ or Proscar® or Avodart® [dutasteride]). Have a history of drug, alcohol, or substance abuse within the past 6 months, as assessed by the investigator. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. Patients who are currently taking TCM for ED treatment within the last 30 days prior to study entry or planned concomitant administration of TCM for ED treatment during study enrolment. Are currently enrolled in, or discontinued with the last 30 days from a clinical trial involving an investigational product or unapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Patients who have been screen failures in other studies may be eligible if they satisfy the inclusion/exclusion criteria. Have a history of loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure. Have rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption lactose intolerance. Are currently in a sexual relationship with a female of child-bearing potential where no form of birth control is being used. A female of child-bearing potential is a female who is not surgically or chemically sterilized and who is between menarche and 1-year post menopause. Are currently in or are planning to be in a sexual relationship with a pregnant female or are currently in a relationship where either partner is actively trying to conceive.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil then Sildenafil<br>20 mg tadalafil taken orally, as needed, for 8 weeks, followed by 100 mg sildenafil taken orally, as needed, for an additional 8 weeks. There is a washout period of 7-10 days between treatments. At the end of the two 8-week treatment periods, participants will be allowed to enter an 8-week extension phase on their preferred medication for erectile dysfunction (ED). | Drug: Tadalafil<br>* Administered Orally<br>* Other names: LY450190;Drug: Sildenafil<br>* Administered Orally<br>|
| Active Comparator: Sildenafil then Tadalafil<br>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 is a washout period of 7-10 days between treatments. At the end of the two 8-week treatment periods, participants will be allowed to enter an 8-week extension phase on their preferred medication for ED. | Drug: Tadalafil<br>* Administered Orally<br>* Other names: LY450190;Drug: Sildenafil<br>* Administered Orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Preferring Tadalafil Over Sildenafil Measured at Week 18 Using Question 1 of the Phosphodiesterase 5 Inhibitor Treatment Preference Questionnaire (PITPQ) | 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. | Week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Moderately or Strongly Preferring the Selected Treatment at Week 18 Using Question 2 of the PITPQ | 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. | Week 18 | 
| Change in International Index of Erectile Function (IIEF) Overall Satisfaction Domain | 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. | Baseline, Week 8, and Week 18 | 
| Change in Sexual Encounter Profile (SEP) Question 2 | 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. | Baseline, Week 8, and Week 18 | 
| Change in Psychosocial and Interpersonal Relationship Scale (PAIRS) Sexual Self-Confidence Domain | 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. | Baseline, Week 8, and Week 18 | 
| Drug Attributes Questionnaire (DRAQ) at Week 18 | 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. | Week 18 | 
| Change in International Index of Erectile Function (IIEF) Intercourse Satisfaction Domain | 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. | Baseline, Week 8, and Week 18 | 
| Change in International Index of Erectile Function (IIEF) Sexual Desire Domain | 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. | Baseline, Week 8, and Week 18 | 
| Change in International Index of Erectile Function (IIEF) Orgasmic Function Domain | 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. | Baseline, Week 8, and Week 18 | 
| Change in Sexual Encounter Profile (SEP) Question 3 | 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. | Baseline, Week 8, and Week 18 | 
| Change in PAIRS Spontaneity Domain | 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. | Baseline, Week 8, and Week 18 | 
| Change in PAIRS Time Concerns Domain | 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. | Baseline, Week 8, and Week 18 | 
| Change in International Index of Erectile Function (IIEF) Erectile Function Domain | 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. | Baseline, Week 8, and Week 18 |