A Study of LY900010 in Erectile Dysfunction

• Percentage of "Yes" responses to Questions 1 through 5 of the Patient Sexual Encounter (SEP) diary [ Time Frame: Baseline through 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 week endpoint in International Index of Erectile Function (IIEF) Domain scores (Intercourse Satisfaction, Orgasmic Function, Sexual Desire, and Overall Satisfaction) [ Time Frame: Baseline through 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 week endpoint in the percentage of subjects who return to "normal" on the International Index of Erectile Function (IIEF) scale (EF>25) [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 week endpoint in Erectile Function (EF) Domain of International Index or Erectile Function (IIEF) in different baseline testosterone concentration subgroups [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 week endpoint in Prostate-Specific Antigen (PSA) [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 week endpoint in lipid profile [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 week endpoint in fasting glucose [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline to 12 week endpoint in fasting insulin [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]

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.

• Drug: LY2452473
  Administered orally, once daily for 12 weeks
• Drug: tadalafil
  Administered orally, once daily for 12 weeks
• Drug: placebo (tadalafil)
  Administered orally, once daily for 12 weeks
• Drug: placebo (LY2452473)
  Administered orally, once daily for 12 weeks

• Experimental: 1 mg LY2452473 + 5 mg tadalafil
  Interventions:

  • Drug: LY2452473
  • Drug: tadalafil
  • Drug: placebo (tadalafil)
• Experimental: 5 mg LY2452473 + 5 mg tadalafil
  Interventions:

  • Drug: LY2452473
  • Drug: tadalafil
  • Drug: placebo (tadalafil)
• Experimental: 5 mg LY2452473 + placebo
  Interventions:

  • Drug: LY2452473
  • Drug: placebo (tadalafil)
• Active Comparator: 10 mg tadalafil + placebo
  Interventions:

  • Drug: tadalafil
  • Drug: placebo (tadalafil)
  • Drug: placebo (LY2452473)
• Active Comparator: 5 mg tadalafil + placebo
  Interventions:

  • Drug: tadalafil
  • Drug: placebo (tadalafil)
  • Drug: placebo (LY2452473)

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 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 arrythmia 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 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 mm Hg or diastolic blood pressure greater than 100 or less than 50 mm Hg at screening
• Hepatic, renal, 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 IU/week, 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