A Study in Men With Low Testosterone to Measure the Effects of Testosterone Solution on Testosterone Levels, Sex Drive and Energy

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate if testosterone solution can raise testosterone hormone levels into the normal range, and also improve levels of sexual arousal, interest and drive and/or energy level, in men with low testosterone and decreased sexual arousal, interest and drive and/or decreased energy. The study will last about 16 weeks, followed by an optional 24 week open label treatment phase to investigate the long term safety of testosterone solution.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Parallel Study With an Open-Label Extension to Assess the Impact of Testosterone Solution on Total Testosterone, Sex Drive and Energy in Hypogonadal Men

Conditions
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Hypogonadism

Intervention / Treatment
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* Drug: Testosterone Solution
* Drug: Placebo Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Total testosterone level <300 nanogram per deciliter (ng/dL) [10.4 nanomole per Liter (nmol/L)] at each of 2 screening visits At least 1 symptom of testosterone deficiency, which must include decreased energy or decreased sexual drive Prostate Specific Antigen (PSA) <4 nanogram per milliliter (ng/ml) at screening Exclusion Criteria: Sexual partner who is or becomes pregnant at any time during the study Use of long-acting intramuscular (IM) testosterone undecanoate or testosterone pellets in the 6-month period prior to screening Body Mass Index (BMI) >37 kilogram per square meter (kg/m^2) at screening Severe lower urinary tract symptoms and/or significant prostate enlargement Prolactin lab test result of >30 ng/mL at screening Hemoglobin A1c (HbA1c) >11% at screening Hematocrit ≥50% (>54% at elevated altitude) at screening Current use of any medications, herbal, and/or nutritional supplements that can interfere with testosterone Dermatologic condition in underarm area that might interfere with testosterone absorption (for example, eczema) or be exacerbated by topical testosterone replacement therapy Currently receiving treatment with cancer chemotherapy or antiandrogens Chronic use of systemic glucocorticoids (use for >14 days within the 3 months prior to screening); use of non-testosterone anabolic steroids within 12 months prior to screening Competitive athletes involved in a sport in which they may be screened for anabolic steroids History of use of estrogenizing agents within 12 months prior to screening History of luteinizing hormone-releasing hormone antagonist or agonist treatment in the last 6 months prior to screening History of clomiphene or other anti-estrogen treatment in the 3 months prior to screening Use of finasteride within 3 months prior to screening, or use of dutasteride within 6 months prior to screening Current use of warfarin or phenprocoumon History of frequent opioid use: >1 time/week during any week within 30 days prior to screening Current use of dopamine receptor agonists (cabergoline, pergolide, bromocriptine) Have a history of significant central nervous system injuries or disease (including stroke, spinal cord injury, or multiple sclerosis) within 6 months prior to screening Systolic blood pressure >170 or <90 millimeter of mercury (mm Hg) or diastolic blood pressure >100 or <50 mm Hg at screening or a history of malignant hypertension History of unstable angina as defined by Braunwald Classification of Unstable Angina or angina occurring during sexual intercourse in the last 6 months History of any of the following coronary conditions within 90 days of screening: myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention (angioplasty or stent placement) Have any supraventricular arrhythmia with an uncontrolled ventricular response [mean heart rate >100 beats per minute (bpm)] at rest, or have any history of spontaneous or induced sustained ventricular tachycardia (heart rate >100 bpm for ≥30 seconds), or use of an automatic internal cardioverter-defibrillator Have a history of sudden cardiac arrest Exhibit any evidence of congestive heart failure [New York Heart Association (NYHA) Class 2 or above], within 6 months prior to screening Have had a new, significant cardiac conduction defect within 90 days prior to screening Clinical suspicion (or history) of prostate cancer during digital rectal examination at screening Known or suspected breast cancer (or history of breast cancer) or other active cancer (with the exception of nonmelanotic skin cancer) Exhibit evidence of severe renal impairment [creatinine clearance <30 milliliter per minute (mL/min) as determined by the Cockcroft-Gault formula] at screening Exhibit a history of severe liver disease or clinical evidence of hepatic impairment at screening Have a history of human immunodeficiency virus (HIV) infection Severe sleep apnea Untreated hypothyroidism, hypercortisolism or other significant endocrinopathy (other than hypogonadism) that contributes to symptoms of low energy or fatigue

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Placebo Comparator: Placebo Solution<br>Placebo Solution applied topically once daily for 12 weeks. | Drug: Placebo Solution<br>* Administered topically to axillae.<br>|
| Experimental: Testosterone Solution<br>Testosterone Solution 60 milligram (mg) applied topically once daily with possible titration down to 30 milligram per day (mg/day) or up to 120 mg/day for 12 weeks and optional extension for 24 weeks. | Drug: Testosterone Solution<br>* Administered topically to axillae.<br>* Other names: LY900011;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Total Serum Testosterone Concentration Within Normal Range at Week 12 | Normal range for total serum testosterone was defined as 300 to 1050 nanograms per deciliter (ng/dL). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in Sexual Arousal, Interest, and Drive (SAID) Scale Scores | The SAID Scale is a self-administered instrument used to assess sexual arousal, interest, and sex drive in men with symptomatic hypogonadism. The SAID consists of 5 questions that were scored on a scale from 1 to 5, with 5 corresponding to greater levels of sexual arousal, interest, or drive. The SAID Scale total score was computed by summing the item scores and linearly transforming the sum to a 0 to 100 scale, with higher scores corresponding to greater sexual arousal, interest, and drive. Least squares (LS) mean change from baseline was calculated using an analysis of covariance (ANCOVA) with treatment group and the baseline value as covariates. | Baseline, Week 12 | 
| Change From Baseline to Week 12 in Hypogonadism Energy Diary (HED) Scores | The HED is a self-administered instrument used to assess real-time energy levels in men with symptomatic hypogonadism. It consists of 2 questions that were scored on a scale from 0 to 10, with 10 corresponding to Full of Energy or Not Tired at All (The Tiredness scale was reverse-mapped, as it was collected with 10 corresponding to Extreme Tiredness). The questionnaire was completed 3 times daily (forming 6 unique items) for 7 consecutive days. Item scores were computed by averaging the values for each item across 7 days. If more than 2 days were missing for an item, the item score was missing. The total score was computed by summing the item scores and linearly transforming the sum to a 0 to 100 scale, with higher scores corresponding to greater energy. If any item score was missing, the total score was missing. LS mean change from baseline was calculated using ANCOVA with treatment group and the baseline value as covariates. | Baseline, Week 12 | 
| Number of Participants With Prostate Specific Antigen (PSA) >4 Nanogram/Milliliter (ng/mL) |  | Double Blind Baseline, Week 12, Open Label Baseline, Week 36 |