A Study of LY900010 in Erectile Dysfunction

Study Overview
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Brief Summary
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The primary purpose of the study is to compare the efficacy of LY2452473 + tadalafil to tadalafil alone in improving the erectile function (EF) of men with erectile dysfunction (ED) who incompletely respond to tadalafil alone.

Official Title
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A Study of LY900010 (LY2452473 + Tadalafil) in the Treatment of Men With Erectile Dysfunction

Conditions
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Erectile Dysfunction

Intervention / Treatment
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* Drug: LY2452473
* Drug: tadalafil
* Drug: placebo (tadalafil)
* Drug: placebo (LY2452473)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include: Ambulatory men History of erectile dysfunction of at least 3 months duration History of incomplete response to any phosphodiesterase type 5 inhibitor (PDE5i) at the maximum tolerated dose within the label Anticipate having the same female sexual partner throughout the duration of the study Are willing and able to make at least 4 sexual intercourse attempts with the female sexual partner during each 4-week segment of the study Agree to use birth control during the study and for 60 days after the study, unless the female partner is postmenopausal Agree not to use any other erectile dysfunction treatment, including herbal treatment, during the study and for 96 hours after the last dose of study drug Screening laboratory tests within normal limits except for testosterone Without a language barrier, are reliable and willing to follow study procedures Prostate-specific antigen (PSA) less than 10 nanograms per milliliter (ng/ml). Men with PSA greater than 4 and less than 10 ng/ml must have documentation of a negative histological biopsy of carcinoma of prostate within 12 months prior to screening Exclusion Criteria include: History of penile implant History of no response to injection therapy for erectile dysfunction History of radical prostatectomy or other pelvic surgery with subsequent failure to achieve any erection Exhibit the presence of clinically significant penile deformity in the opinion of the investigator History of prior sexual legal convictions Bilateral hip replacements History of cancer within the previous 5 years, except for excised superficial lesions such as basal cell carcinoma and squamous cell carcinoma of the skin Chronic stable angina currently treated with long-acting nitrates Chronic stable angina requiring treatment with short-acting nitrates within 90 days prior to screening Angina occurring during sexual intercourse in the 6 months prior to screening Unstable angina within 6 months prior to screening Myocardial infarction or coronary artery bypass graft surgery within 90 days prior to screening Angioplasty or stent placement within 90 days prior to screening Congestive heart failure within 6 months prior to screening History of sudden cardiac arrest Supraventricular arrhythmia with an uncontrolled ventricular response at rest, or any history of spontaneous or induced sustained ventricular tachycardia, or use an automatic internal cardioverter-defibrillator An abnormality in the 12-lead electrocardiogram (ECG) that in the opinion of the investigator places the subject in an unacceptable risk for study participation Systolic blood pressure greater than 170 or less than 90 millimeters of mercury (mm Hg) or diastolic blood pressure greater than 100 or less than 50 mm Hg at screening Hepatic, renal, human immunodeficiency virus (HIV), or clinically significant active neuropsychiatric disease History of central nervous system injuries (including stroke or spinal cord injury) within 6 months prior to screening Alcohol intake of 5 units or greater per day (1 unit = 12 ounces beer, 5 ounces wine, or 1.5 ounces of 80-proof distilled spirits) Receiving treatment with antiandrogens or 5-alpha reductase inhibitor Anabolic steroids, calcitonin, oral bisphosphonates, Vitamin D greater than 50,000 international units per week (IU/week), dehydroepiandrosterone (DHEA), steroidal supplements, nutritional products intended to have weight reduction or performance enhancing effects, herbal supplements within 7 days prior to screening Currently treated with a potent cytochrome P450 (CYP) 3A4 inhibitor, such as systemic ketoconazole or ritonavir, or a CYP3A4 inducer such as rifampicin

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 milligram (mg) LY2452473 + 5 mg tadalafil<br> | Drug: LY2452473<br>* Administered orally, once daily for 12 weeks<br>Drug: tadalafil<br>* Administered orally, once daily for 12 weeks<br>Drug: placebo (tadalafil)<br>* Administered orally, once daily for 12 weeks<br>|
| Experimental: 5 mg LY2452473 + 5 mg tadalafil<br> | Drug: LY2452473<br>* Administered orally, once daily for 12 weeks<br>Drug: tadalafil<br>* Administered orally, once daily for 12 weeks<br>Drug: placebo (tadalafil)<br>* Administered orally, once daily for 12 weeks<br>|
| Experimental: 5 mg LY2452473 + placebo<br> | Drug: LY2452473<br>* Administered orally, once daily for 12 weeks<br>Drug: placebo (tadalafil)<br>* Administered orally, once daily for 12 weeks<br>|
| Active Comparator: 10 mg tadalafil + placebo<br> | Drug: tadalafil<br>* Administered orally, once daily for 12 weeks<br>Drug: placebo (tadalafil)<br>* Administered orally, once daily for 12 weeks<br>Drug: placebo (LY2452473)<br>* Administered orally, once daily for 12 weeks<br>|
| Active Comparator: 5 mg tadalafil + placebo<br> | Drug: tadalafil<br>* Administered orally, once daily for 12 weeks<br>Drug: placebo (tadalafil)<br>* Administered orally, once daily for 12 weeks<br>Drug: placebo (LY2452473)<br>* Administered orally, once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12 Week Endpoint in International Index of Erectile Function (IIEF) Erectile Function (EF) Domain Score | The IIEF EF domain score was the sum of Questions (Q) 1 to Q5 and Q15 of the IIEF self-reported questionnaire. Q1 to Q5 were rated 0 (low/no EF) to 5 (high EF) and Q15 was rated 1 (no/low confidence) to 5 (high confidence). IIEF EF domain scores ranged from 1 to 30. Higher scores denoted better EF. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 12 Week Endpoint in the Percentage of Yes Responses on the Sexual Encounter Profile (SEP) Diary | The SEP diary was a participant-assessed diary with 5 questions (Q): Q1 (erection achievement), Q2 (successful penetration), Q3 (successful intercourse), Q4 (satisfied with erection), and Q5 (satisfied with sexual experience) for each sexual encounter made over a specified period of time. SEP Q1 to Q5 scores were determined as a percentage of Yes responses to each of the 5 questions out of all sexual attempts recorded during the time period. A higher percentage of Yes responses indicated better EF. Assessed was the mean change from baseline in the percentage of Yes responses to the SEP diary Q1 to Q5. The least squares (LS) mean was estimated from a repeated measures analysis of covariance model that included terms for treatment, visit, treatment*visit, baseline, baseline*treatment (if p-value <0.25). | Baseline, Week 12 | 
| Change From Baseline to 12 Week Endpoint in IIEF Domain Scores (Intercourse Satisfaction, Orgasmic Function, Sexual Desire, and Overall Satisfaction) | Intercourse Satisfaction (IS) domain score: sum of Questions (Q) 6, Q7, and Q8, each rated 0 (low/no satisfaction) to 5 (high satisfaction). IS domain score range: 0 to 15; lower scores denoted lower satisfaction. Orgasmic Function (OF) domain score: sum of Q9 and Q10, each rated 0 (no sexual stimulation) to 5 (almost always/always). OF domain score range: 0 to 10; lower scores denoted lower OF. Sexual Desire (SD) domain score: sum of Q11 and Q12, each rated 1 (almost never or low/no sexual desire) to 5 (almost always or very high sexual desire). SD domain score range: 2 to 10; lower scores denoted lower SD. Overall Satisfaction (OS) domain score: sum of Q13 and Q14, each rated 1 (low/no satisfaction) to 5 (high satisfaction). OS domain score range: 2 to 10; lower scores denoted lower OS. Least squares (LS) mean estimated from repeated measures analysis of variance model that included terms for treatment, visit, treatment*visit, baseline, baseline*treatment (if p-value<0.25). | Baseline, Week 12 | 
| Change From Baseline to 12 Week Endpoint in the Percentage of Participants Who Return to Normal on the International Index of Erectile Function (IIEF) Scale (EF>25) | The percentage of participants whose IIEF Erectile Function (EF) domain scores changed from ≤25 at baseline to >25 (normal) at Week 12. The IIEF EF domain score was the sum of IIEF Question (Q) 1 to Q5 and Q15. Q1 to Q5 were rated 0 (low/no EF) to 5 (high EF) and Q15 was rated 1 (no/low confidence) to 5 (high confidence). IIEF EF domain scores ranged from 1 to 30. Higher scores denoted better EF. | Baseline, Week 12 | 
| Change From Baseline to 12 Week Endpoint in IIEF EF Domain Score Reported by Testosterone Concentration Subgroups | The International Index of Erectile Function (IIEF) EF was the sum of Questions (Q) 1 to Q5 and Q15 of the IIEF Self-reported questionnaire. Q1 to Q5 were rated 0 (low/no erectile function) to 5 (high erectile function) and Q15 was rated 1 (no/low confidence) to 5 (high confidence). IIEF EF domain scores ranged from 1 to 30. Higher scores denoted better EF. Testosterone concentration subgroups were based on optimal baseline testosterone levels (<340 nanograms per deciliter [ng/dL] or ≥340 ng/dL). The least squares (LS) mean was estimated from an analysis of covariance (ANCOVA) model that included terms for treatment group, baseline, and baseline*treatment interaction (if p-value<0.25). | Baseline, Week 12 | 
| Change From Baseline to 12 Week Endpoint in Prostate-Specific Antigen (PSA) | The least squares (LS) mean was estimated from a repeated measures analysis of covariance model that included terms for treatment, visit, treatment*visit, baseline, baseline*treatment (if p-value<0.25). | Baseline, Week 12 | 
| Change From Baseline to 12 Week Endpoint in Total Cholesterol and Triglycerides | The least squares (LS) mean was estimated from a repeated measures analysis of covariance model that included terms for treatment, visit, treatment*visit, baseline, baseline*treatment (if p-value<0.25). | Baseline, Week 12 | 
| Percent Change From Baseline to 12 Week Endpoint in High-Density Lipoprotein Cholesterol (HDL-C) and Low-Density Lipoprotein Cholesterol (LDL-C) | The least squares (LS) was estimated from a repeated measures analysis of covariance model that included terms for treatment, visit, treatment*visit, baseline, baseline*treatment (if p-value<0.25). | Baseline, Week 12 | 
| Change From Baseline to 12 Week Endpoint in Fasting Glucose | The least squares (LS) mean was estimated from a repeated measures analysis of covariance model that included terms for treatment, visit, treatment*visit, baseline, baseline*treatment (if p-value<0.25). | Baseline, Week 12 | 
| Change From Baseline to 12 Week Endpoint in Fasting Insulin | Change from baseline to 12 Week endpoint in fasting blood insulin concentration. The least squares (LS) mean was estimated from a repeated measures analysis of covariance model that included terms for treatment, visit, treatment*visit, baseline, baseline*treatment (if p-value<0.25). | Baseline, Week 12 |