Safety and Efficacy of BGS649 in Obese, Hypogonadotropic Hypogonadal Men

Phase 2

Terminated

Brief Summary: 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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo to BGS649 (Part 2)	Placebo	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).

Primary Outcome Measures

Name	Time	Method
Part 2: Change From Baseline at Homeostatic Model Assessment of Insulin Resistance (HOMA-IR & QUICKI Scores) at Week 4 and 12	Baseline, Week 4 and Week 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.
Percentage of Patients Achieving Normal Testosterone Levels	At Week 4 and 12	Percentage of patients achieving normal testosterone (2.50 - 9.50 ng/mL) levels at Week 4 and Week 12

Secondary Outcome Measures

Name	Time	Method
Part 2: Pharmacokinetics of BGS649: Time to Reach Maximum (Peak) Blood Drug Concentration After Single Dose Administration (Tmax)	Week 1 to Week 11	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.
PK of BGS649 Elimination Half-life Associated With the Terminal Slope of a Semi Logarithmic Concentration-time Curve (T1/2)	Week 1 to Week 11	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.
Part 2: Area Under the Concentration-time Curve From Time Zero to Time 't' (AUC0-168)	11 weeks	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.
Part 2: Pharmacokinetics of BGS649: Maximum (Peak) Observed Blood Drug Concentration After Single Dose Administration (Cmax)	Week 1 to Week 11	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.