Hypogonadotropic hypogonadism (HH) MedDRA version: 20.0 Level: LLT Classification code 10021012 Term: Hypogonadotrophic hypogonadism System Organ Class: 100000004860
Conditions
Interventions
Product Code: BGS649
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not established
CAS Number: 143030-47-1
Current Sponsor code: BGS649
Other descriptive name: Fluor-DCP-triazol
Concentratio
Sponsors
Mereo BioPharma 2 Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Adult male subject aged 18 to 65 years inclusive 2. BMI > 30 kg/m2 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Evidence of clinically significant endocrinopathy at Screening that may interfere with the study assessments or mask/mimic symptoms of hypogonadism e.g., growth hormone deficiency, adrenal deficiency, untreated hypothyroidism (primary hypothyroidism on replacement with normal thyroid stimulating hormone [TSH] level is allowed), or that may interfere with the evaluation of efficacy/safety parameters 2. Other types of HH (e.g., Kallmann syndrome) or primary hypogonadism (e.g., cryptorchidism, or Klinefelter syndrome) 3. Any other pituitary or hypothalamic disease, as based on one of the following: - Current or past hypothalamic or pituitary tumour - Suspicion of pituitary or hypothalamic tumour based on a clinical or laboratory evidence, e.g., elevated prolactin or other pituitary hormone abnormality, symptoms/signs of tumour mass effect, very low testosterone and LH (unless there is documentation of a normal magnetic resonance imaging scan of pituitary and hypothalamus within 3 months before first Screening Visit) - Hypothalamic or pituitary conditions, which may contribute to hypogonadism e.g., pituitary sarcoidosis, histiocytosis or tuberculosis 4. Subject with prostate disease, as confirmed by the presence of one of the following: - History of prostate cancer - Elevated PSA levels = 3 ng/mL at Screening - Subjects with a detectable prostate nodule or induration at Screening unless proven previously benign by a biopsy - Urologist confirmed symptomatic benign prostatic hyperplasia 5. History of type 1 diabetes mellitus 6. Current clinical diagnosis of depression or current or past Bipolar disorder 7. Uncontrolled type 2 diabetes mellitus (HbA1c > 10.5% at Screening) or significant diabetic neuropathy. Subjects with type 2 diabetes can be included when both of the following conditions are met: - HbA1c = 10.5% at Screening, and: - Anti-diabetic medication regimen (excluding insulin) has been stable for = 8 weeks before the first Screening visit 8. Treatment with one or more of the following prescribed or over the counter medications in the six months prior to first Screening Visit: - Medications with known androgenic or estrogenic properties or known to affect production of sex hormones - Injectable testosterone enhancement therapy - Fertility drugs - Growth hormone - Anabolic steroids - Long acting opiates 9. Treatment with topical testosterone therapy in the two months prior to first Screening Visit 10. Treatment with one of the following medications for either >7 consecutive days in the three months prior to first Screening Visit OR any treatment within 3 weeks of first Screening Visit: - Testosterone lowering drugs e.g., spironolactone, cimetidine, 5a-reductase inhibitors - Short acting opiates / opioids including methadone - Medications known to increase prolactin levels, e.g., antipsychotics 11. Treatment with the following medications: - Chronic systemic steroid treatment or systemic steroids for > 5 consecutive days for intercurrent illness within the 4 weeks prior to the first Screening visit (inhaled and topical steroids are allowed) - Clomid within 1 year before first Screening Visit - Biphosphonates or other medication used to treat low bone density (denosumab, teriparatide) except calcium and vitamin D within 1 year before first Screening Visit 12. Weight loss or weight gain (gain or loss > 5% body weight) OR weight reduction surgery or procedure within the 3 months prior to first Screenin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 24;Main Objective: The primary objective is to demonstrate the efficacy of BGS649 to normalise total testosterone levels (300-1000 ng/dL [10.4-35 nmol/L]) in = 75% of subjects after 24 weeks of treatment.;Primary end point(s): 1. Normalisation of total testosterone levels in = 75% of subjects at Week 24.;Secondary Objective: Secondary Objectives 1. To follow the time-course of normalisation in total testosterone levels 2. To demonstrate the efficacy of BGS649 to normalise total testosterone levels in = 90% of subjects after 24 weeks of treatment 3. To evaluate the effect of BGS649 on luteinising hormone (LH) and follicle stimulating hormone (FSH) 4. To further determine the pharmacokinetics (PK) of BGS649. Safety Objectives: 1. To evaluate safety and tolerability of BGS649. Exploratory Objectives: 1. To evaluate the effect of BGS649 on oestradiol, DHT and inhibins (A and B) 2. To evaluate the effect of BGS649 on testosterone/oestradiol ratio 3. To investigate patient reported outcomes (PROs) following treatment with BGS649. Evaluated PROs will include: - Sexual function (IIEF & PROMIS SexFS) - Energy/fatigue (Brief Fatigue Inventory [BFI]) - SF-36 Quality of life (QoL) questionnaire - Patient Global Impression (PGI-S) For additional Exploratory Objectives refer to the protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary 1. Proportion of subjects that have normalisation of total testosterone to Week 24 2. Proportion of subjects that overshoot testosterone (total testosterone above 1000 ng/dL [35 nmol/L]) to Week 24 3. Normalisation of total testosterone in = 90% subjects to Week 24 4. Change of LH and FSH at 24 weeks 5. Population PK analysis of plasma BGS649 concentrations 6. PK analysis of semen BGS649 concentrations. Exploratory 1. Change in oestradiol, inhibins (A and B) levels and DHT 2. Change in testosterone/oestradiol ratio 3. Body composition changes at Week 12 and Week 24 4. Changes in markers of cardiometabolic disease: blood pressure, lipid profile, HbA1c, glucose and insulin, hs-CRP and HOMA-IR and association with change in body composition and testosterone level. 5. Change in markers of bone turnover in those with and without 25 hydroxy vitamin D deficiency 6. Change in total and domain scores on PRO measures (IIEF, PROMIS SexFS: to assess sexual function; BFI, PROMIS Fatigue Short Form, SF-36 - Vitality: to assess energy levels and fatigue; SF-36: to assess general quality of life (QoL); PGI-S: to assess the patients’ impression of their current health status) over the 24 week period. 7. Change in physical activity, sleeping pattern and strength measured by wrist worn monitors and grip strength measurement at 12 and 24 weeks and association with body composition (as measured by BMI and waist circumference and impedance) and testosterone level. 8. PK/pharmacodynamic (PD) relationship between BGS649 concentrations and testosterone levels 9. For semen analysis: change in semen parameters throughout the study and association with LH/FSH level 10. Change in bioavailable testosterone 11. Time to first normal testosterone level. Safety 1. Treatment emergent AEs (TEAEs)/SAEs (from first dose of study drug until 90 days after last treatment dose) 2. Change in PSA during 24 week treatment duration 3. Change in haematoc | — |
Countries
Italy, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactProject management
ICON Clinical Research
Outcome results
None listed