Safety and Efficacy of BGS649 in Male Obese Subjects With Hypogonadotropic Hypogonadism

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of BGS649 in male obese subjects with hypogonadotropic hypogonadism. All subjects will be treated for a maximum of 24 weeks. Some subjects who complete 24 weeks of treatment will be invited to participate in a 6-month blinded safety extension study (Protocol MBGS206). The study is planned to enroll 268 subjects.

Official Title
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A Phase IIb Multicentre, Double-Blind, Dose-Ranging, Randomised, Placebo-Controlled Study Evaluating Safety and Efficacy of BGS649 in Male Obese Subjects With Hypogonadotropic Hypogonadism

Conditions
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Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: BGS649
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male subject aged 18 to 65 years inclusive BMI > 30 kg/m2 and < 50 kg/m2 Serum total testosterone concentration below the normal range LH levels below the upper limit of normal Oestradiol levels within or above the normal range of approved assay At least two symptoms of androgen deficiency present for at least 2 months prior to the first Screening Visit, with at least one of these being a sexual dysfunction Exclusion Criteria: Evidence of clinically significant endocrinopathy at screening that may interfere with the study assessments Other types of hypogonadotropic hypogonadism or primary hypogonadism Any other pituitary or hypothalamic disease

Ages Eligible for Study
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Minimum Age: 18 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 0.1 mg<br>BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) | Drug: BGS649<br>* Capsules were taken weekly for a maximum of 24 weeks<br>|
| Experimental: BGS649 0.3 mg<br>BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) | Drug: BGS649<br>* Capsules were taken weekly for a maximum of 24 weeks<br>|
| Experimental: BGS649 1.0 mg<br>BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) | Drug: BGS649<br>* Capsules were taken weekly for a maximum of 24 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo weekly (3 indistinguishable placebo capsules) | Drug: Placebo<br>* Capsules were taken weekly for a maximum of 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Normalised Testosterone After 24 Weeks of Study Treatment | Percentage of patients with normalised testosterone i.e. testosterone in the range 300-1000ng/dL after 24 weeks of study treatment. The primary objective was considered met, if greater than or equal to 75% of the participants in any arm normalised. | 24 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects That Have Normalization of Total Testosterone Serum Concentrations From Baseline to Week 24 | Normalised total testosterone level was defined as between 300-1000 ng/dL (10.4-35 nmol/L) inclusive. Levels >1000 ng/dL were considered super-physiological outside the normal range. | Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks | 
| Proportion of Subjects That Overshoot Testosterone (Total Testosterone Above 1000 ng/dL [35 Nmol/L]) From Baseline to Week 24 | Testosterone overshoot was defined as total testosterone above 1000 ng/dL (35 nmol/L). Samples were collected in the morning before 11 am pre dose. | Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks | 
| Normalization of Total Testosterone Serum Concentrations in ≥ 90% Subjects After 24 Weeks of Treatment. | Normalized total testosterone level was defined as between 300-1000 ng/dL (10.4-35 nmol/L) inclusive. Levels >1000 ng/dL were considered super-physiological outside the normal range. This secondary outcome measure was considered to have been met for a dose if ≥ 90% of subjects in the intent-to-treat (ITT) population had normalisation of total testosterone levels at Week 24. | 24 weeks of treatment | 
| Mean (SD) Change From Baseline in Luteinizing Hormone (LH) to Week 24. | LH was measured at screening, baseline. The Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. | Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks | 
| Mean (SD) Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 24. | FSH was measured at baseline, Visit 1 through 8 and follow-up. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. | Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks | 
| Descriptive Summary (Geometric Mean [95% CI]) of BGS649 Plasma PK Concentration Values to 24 Weeks. | Plasma PK sampling for BGS649 was performed at Weeks 12 and 24. BGS649 PK plasma concentrations were summarised for the PK population by descriptive statistics. | Week 12 (pre-dose and 1 hour post-dose), week 24 and week 24/End of treatment | 
| Descriptive Summary (Geometric Mean [95% CI]) of BGS649 Semen PK Concentration Values at 24 Weeks. | Semen PK sampling for BGS649 was performed at Visit 8 (End of Treatment). BGS649 PK semen concentrations were summarised for the PK population by descriptive statistics. | Week 24 and week 24/End of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypogonadotropic, hypogonadism, testosterone