Safety and Efficacy of BGS649 in Obese, Hypogonadotropic Hypogonadal Men

Study Overview
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Brief Summary
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This study is designed as a 2-part study, with Part 1 being open-label to best determine the appropriate dose levels to use in Part 2, which has a randomized, double-blind, placebo controlled design. The study aims to assess the safety and tolerability of BGS649, and determine whether or not BGS649 is able to normalize testosterone levels and improve insulin sensitivity in obese, hypogonadotropic hypogonadal (OHH) men

Official Title
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An Open-label Dose Finding Study Followed by a Parallel Group, Randomized, Double-blind Study to Evaluate the Safety, Tolerability and Pharmacodynamics of 12 Week BGS649 Treatment in Obese, Hypogonadotropic Hypogonadal Men

Conditions
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Obese Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: Investigational new drug company code: BGS649
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males who meet the criteria of obese, hypogonadotropic hypogonadism defined as: Patients with a Body Mass Index (BMI) ≥ 30 kg/m2 Patients with a morning serum total testosterone level < 300 ng/dL on at least two separate occasions during the Screening and/or Baseline periods. Patients with inappropriately low gonadotropins at screening given the low testosterone: Luteinizing hormone (LH) ≤ ULN Follicle stimulating hormone (FSH) ≤ ULN Estradiol within or above the normal range (defined as ≥ LLN of the approved assay) Normal hypothalamic/pituitary function, including: Prolactin: within the normal range Thyroid stimulating hormone (TSH): within the normal range Ferritin: within the normal range Patients agree to use a barrier method of contraception (e.g., condom), for the duration of the study and for at least 3 months following their Study Completion visit to prevent BGS649 exposure to their partners. Exclusion Criteria: Patients with hypogonadism, not related to obesity or as a result of other underlying issues Patients with significant major organ class illness (e.g. kidney or liver disease). Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 30 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGS649 (Part 1)<br>BGS649 1mg and 0.1mg in hard gelatin capsules. In part 1 there was individualised dosing to titrate the subject's testosterone into the normal range. If the dose was lower than 0.1mg then specific instructions for dilution of an oral solution of BGS649 were provided. | Drug: Investigational new drug company code: BGS649<br> <br> |
| Placebo Comparator: Placebo to BGS649 (Part 2)<br>Matching placebo to BGS649 (0.3 and 0.1mg). 0.3mg placebo capsule given on Day 1 and 0.1mg placebo capsule on other treatment visits (week 1 to 11). | Drug: Placebo<br> <br> |
| Experimental: BGS649 (Part 2)<br>0.3 or 0.1mg hard gelatin capsules of BGS649 given orally. 0.3mg on Day 1 and 0.1 on all other treatment visits (week 1 to 11). | Drug: Investigational new drug company code: BGS649<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving Normal Testosterone Levels | Percentage of patients achieving normal testosterone (2.50 - 9.50 ng/mL) levels at Week 4 and Week 12 | At Week 4 and 12 | 
| Part 2: Change From Baseline at Homeostatic Model Assessment of Insulin Resistance (HOMA-IR & QUICKI Scores) at Week 4 and 12 | Pharmacodynamic change from baseline in HOMA-IR. Score at week 4 and week 12 as an assessment of insulin resistance. Low score representing high insulin sensitivity and a high score representing low insulin sensitivity or insulin resistance. HOMA-IR is a ration of Fasting insulin (mIU/L) : Fasting glucose (mmol). Pharmacodynamic change in QUICKI score at week 4 and week 12 as an assessment of insulin resistance. The QUICKI scale is a log score and a high score representing high insulin sensitivity and low score indicating low insulin sensitivity. Patients with a score below 0.3 are considered diabetic. Week 12 data is missing because there were inaccuracies in dosing of patients and so the study was terminated, only safety data was collected. | Baseline, Week 4 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Area Under the Concentration-time Curve From Time Zero to Time 't' (AUC0-168) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. The AUC 0-168 measures the amount of drug within the subjects blood over the 168h post-dosing at these timepoints. | 11 weeks | 
| Part 2: Pharmacokinetics of BGS649: Maximum (Peak) Observed Blood Drug Concentration After Single Dose Administration (Cmax) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | Week 1 to Week 11 | 
| Part 2: Pharmacokinetics of BGS649: Time to Reach Maximum (Peak) Blood Drug Concentration After Single Dose Administration (Tmax) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | Week 1 to Week 11 | 
| PK of BGS649 Elimination Half-life Associated With the Terminal Slope of a Semi Logarithmic Concentration-time Curve (T1/2) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | Week 1 to Week 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obese, obesity, hypogonadism, hypogonadotropic, hyperestrogenemic, testosterone, hypogonadal