A Study in Men With Benign Prostatic Hyperplasia

Study Overview
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Brief Summary
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The purpose of the study is to determine whether LY500307 helps symptoms of Benign Prostatic Hyperplasia (BPH)

Official Title
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A Phase 2 Clinical Study to Evaluate Daily Oral Doses of LY500307 for 24 Weeks in Men With Lower Urinary Tract Symptoms (LUTS) and Prostatic Enlargement Secondary to Benign Prostatic Hyperplasia (BPH)

Conditions
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Benign Prostatic Hyperplasia

Intervention / Treatment
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* Drug: LY500307
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Present at screening with a history of benign prostatic hyperplasia (BPH) for >6 months. Have an International Prostate Symptom Score (IPSS) greater than or equal to 13 at screening. Have a total prostate volume by transrectal ultrasound greater than or equal to 30 milliliter (mL) at screening. Show signs of bladder outlet obstruction as defined by a peak urinary flow rate (Qmax) greater than or equal to 4 and less than or equal to 15 milliliter/second (mL/sec) (from a prevoid total bladder volume [assessed by ultrasound] of greater than or equal to 150 to less than or equal to 550 ml and a minimum voided volume of 125 ml) at screening. Have a prostate-specific antigen (PSA) greater than or equal to 1.4 and less than or equal to 10 nanogram/milliliter (ng/mL) at screening. Demonstrate a Post Void Residual less than or equal to 300 mL by ultrasound at screening. Have not received the following treatments within the specified time period: Finasteride or dutasteride for at least 6 months prior to screening. Any alpha-adrenergic antagonists for at least 4 weeks prior to screening. Any other non-experimental BPH therapy (including an herbal preparation) for at least 4 weeks prior to screening. Any other experimental or off-label BPH therapy such as injectable therapies with a protracted effect for at least 6 months prior to screening. Any overactive bladder treatment for at least 4 weeks prior to screening. Any Erectile Dysfunction treatment which may include oral phosphodiesterase type 5 inhibitors or devices for at least 4 weeks prior to screening. Have a morning fasting Total Testosterone concentration greater than or equal to 300 nanogram/deciliter (ng/dL) at screening. If hyperlipidemic, based on history, be stable on statin treatment as determined by the investigator for at least 2 months prior to screening. Exclusion Criteria: Have completed or withdrawn from this study or have completed or withdrawn from any other study investigating LY500307. Have any history of BPH-related invasive procedures (for example, Transurethral Resection of the Prostate, open prostatectomy, and minimally invasive procedures that include thermal-based therapies, transurethral microwave treatment, transurethral needle ablation, and stents). Have active cardiovascular disease as evidenced by the following: Recent Myocardial infarction, unstable angina, stroke or Transient ischemic attack within 6 months of screening. Recent coronary intervention that includes coronary artery bypass surgery, percutaneous coronary artery intervention, or stent placement within 6 months of screening. Recent history of positive stress tests without any written documentation of effective intervention within 6 months of screening. Evidence of heart disease categorized as greater than or equal to Class III functional classification of New York Heart Association (NYHA) within 6 months of screening. Have known or suspected history of prostate cancer, breast cancer, or other clinically significant neoplastic disease (other than squamous cell or basal cell carcinoma of skin). Have a history of deep venous thrombosis or pulmonary embolism disease. Have moderate to severe renal insufficiency. Have a hemoglobin A1c (HbA1c) greater than 9.0%. Are on testosterone replacement therapy, or drugs that influence the hypothalamus-pituitary-gonadal axis. Are on pharmacological treatment other than statins for hyperlipidemia.

Ages Eligible for Study
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Minimum Age: 45 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1mg LY500307<br> | Drug: LY500307<br>* Administered orally, daily for 24 weeks<br>|
| Experimental: 3mg LY500307<br> | Drug: LY500307<br>* Administered orally, daily for 24 weeks<br>|
| Experimental: 10mg LY500307<br> | Drug: LY500307<br>* Administered orally, daily for 24 weeks<br>|
| Experimental: 25mg LY500307<br> | Drug: LY500307<br>* Administered orally, daily for 24 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Administered orally, daily for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 24-Week Endpoint in International Prostate Symptom Score (IPSS) Total Score | IPSS Total Score is the sum of Questions 1 through 7 of the IPSS questionnaire. Each question is scored from 0 (none/no symptoms) to 5 (frequent symptoms) with an IPSS Total Score range of 0-35 points. Higher numerical scores from the IPSS questionnaire represent greater severity of symptoms. | Baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline to 24-Week Endpoint in Total Prostate Volume (TPV) | The TPV measurement (milliliters) by transrectal ultrasound (TRUS) is an established diagnostic test for men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). | Baseline, 24 weeks | 
| Change From Baseline to 24-Week Endpoint in Peak Urinary Flow Rate (Qmax) | Qmax is defined as the peak urine flow rate measured using standard calibrated uroflowmeter. | Baseline, 24 weeks | 
| Change From Baseline to 24-Week Endpoint in International Prostate Symptom Score-Quality of Life Index (IPSS-QoL) | IPSS QoL assesses participant's response to the following question: If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that? Response options are Delighted (0), Pleased (1); Mostly satisfied (2); Mixed-about equally satisfied and dissatisfied (3); Mostly dissatisfied (4); Unhappy (5); Terrible (6), with a total range of 0-6. | Baseline, 24 weeks | 
| Change From Baseline to 24-Week Endpoint in International Prostate Symptom Score (IPSS) Storage, Voiding and Nocturia Subscores | IPSS Storage (Irritative) subscore is the sum of Questions 2, 4 and 7 of the IPSS questionnaire. Scores range from 0 (no irritative symptoms) to 5 (frequent irritative symptoms), with a total subscore of the 3 questions for irritative subscore ranging from 0 to 15. IPSS Voiding (Obstructive) subscore is the sum of Questions 1, 3, 5 and 6 of the IPSS questionnaire. Scores range from 0 (no obstructive symptoms) to 5 (frequent obstructive symptoms), with a total subscore of the 4 questions of the obstructive score ranging from 0 to 20. Nocturia Subscore is IPSS Question 7, which assesses how many times over the last month a participant gets up to urinate from the time they went to bed at night until the time they got up in the morning. Scores range from 0=None; 1=1 time; 2= 2 times; 3=3 times; 4=4 times; 5=5 or more times. | Baseline, 24 weeks | 
| Percentage Change From Baseline to 24-Week Endpoint in Prostate Specific Antigen (PSA) | The units of PSA measurement are nanograms per milliliter (ng/mL). | Baseline, 24 weeks | 
| Change From Baseline to 24-Week Endpoint in Fasting Total Testosterone |  | Baseline, 24 weeks | 
| Change From Baseline to 24-Week Endpoint in Lipid Profile | The lipid profile consisted of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. | Baseline, 24 weeks |