Safety and Efficacy of BGS649 in Obese, Hypogonadotropic Hypogonadal Men

NCT01200862 | Terminated Phase 2 Results

• 1 other identifier: CBGS649A2204
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 5

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

Conditions

Obese Hypogonadotropic Hypogonadism

Keywords

Obese; obesity; hypogonadism; hypogonadotropic; hyperestrogenemic; testosterone; hypogonadal

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Part 2: Area Under the Concentration-time Curve From Time Zero to Time 't' (AUC0-168)

  11 weeks

• Part 2: Pharmacokinetics of BGS649: Maximum (Peak) Observed Blood Drug Concentration After Single Dose Administration (Cmax)

  Week 1 to Week 11

• Part 2: Pharmacokinetics of BGS649: Time to Reach Maximum (Peak) Blood Drug Concentration After Single Dose Administration (Tmax)

  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)

  Week 1 to Week 11

Study Arms (3)

BGS649 (Part 1)

EXPERIMENTAL

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

Placebo to BGS649 (Part 2)

PLACEBO COMPARATOR

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

BGS649 (Part 2)

EXPERIMENTAL

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

Interventions

Investigational new drug company code: BGS649 DRUG

BGS649 (Part 1); BGS649 (Part 2)

Placebo DRUG

Placebo to BGS649 (Part 2)

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Mereo BioPharma: lead
• Novartis: collaborator

Study Sites (5)

Novartis Investigative Site

Tucson, Arizona, 85712, United States

Location

Novartis Investigative Site

San Diego, California, 92120, United States

Location

Novartis Investigative Site

Miramar, Florida, 33025, United States

Location

Novartis Investigative Site

West Valley City, Utah, 84120, United States

Location

Novartis Investigative Site

Montreal, Quebec, H3X 2H9, Canada

Location

MeSH Terms

Conditions

Obesity; Hypogonadism

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Gonadal Disorders; Endocrine System Diseases

Limitations and Caveats

Part 2 of the study was early terminated due to incorrect dosing, therefore only 8 of the 15 subjects enrolled completed 11 doses of treatment, and the remaining 7 subjects had incomplete dosing.

Results Point of Contact

• Title: Dr. Jackie Parkin
• Organization: Mereo BioPharma

enquiries@mereobiopharma.com

+44 333 0237300

Study Officials

• Jacqueline Parkin, PhD FRCP

  Mereo BioPharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Open-label in Part 1 and double-blind in Part 2.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2010
• First Posted: September 14, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 8, 2020
• Results First Posted: October 8, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (4)