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Safety and Efficacy of BGS649 in Obese, Hypogonadotropic Hypogonadal Men (OHH)

Primary Purpose

Obese Hypogonadotropic Hypogonadism

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Investigational new drug company code: BGS649
Placebo
Sponsored by
Mereo BioPharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obese Hypogonadotropic Hypogonadism focused on measuring Obese, obesity, hypogonadism, hypogonadotropic, hyperestrogenemic, testosterone, hypogonadal

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

BGS649 (Part 1)

Placebo to BGS649 (Part 2)

BGS649 (Part 2)

Arm Description

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.

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).

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).

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
September 10, 2010
Last Updated
October 5, 2020
Sponsor
Mereo BioPharma
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT01200862
Brief Title
Safety and Efficacy of BGS649 in Obese, Hypogonadotropic Hypogonadal Men
Acronym
OHH
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Study Start Date
August 2010 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mereo BioPharma
Collaborators
Novartis

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obese Hypogonadotropic Hypogonadism
Keywords
Obese, obesity, hypogonadism, hypogonadotropic, hyperestrogenemic, testosterone, hypogonadal

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Open-label in Part 1 and double-blind in Part 2.
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BGS649 (Part 1)
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo to BGS649 (Part 2)
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
BGS649 (Part 2)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Investigational new drug company code: BGS649
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percentage of Patients Achieving Normal Testosterone Levels
Description
Percentage of patients achieving normal testosterone (2.50 - 9.50 ng/mL) levels at Week 4 and Week 12
Time Frame
At Week 4 and 12
Title
Part 2: Change From Baseline at Homeostatic Model Assessment of Insulin Resistance (HOMA-IR & QUICKI Scores) at Week 4 and 12
Description
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.
Time Frame
Baseline, Week 4 and Week 12
Secondary Outcome Measure Information:
Title
Part 2: Area Under the Concentration-time Curve From Time Zero to Time 't' (AUC0-168)
Description
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.
Time Frame
11 weeks
Title
Part 2: Pharmacokinetics of BGS649: Maximum (Peak) Observed Blood Drug Concentration After Single Dose Administration (Cmax)
Description
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.
Time Frame
Week 1 to Week 11
Title
Part 2: Pharmacokinetics of BGS649: Time to Reach Maximum (Peak) Blood Drug Concentration After Single Dose Administration (Tmax)
Description
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.
Time Frame
Week 1 to Week 11
Title
PK of BGS649 Elimination Half-life Associated With the Terminal Slope of a Semi Logarithmic Concentration-time Curve (T1/2)
Description
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.
Time Frame
Week 1 to Week 11

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacqueline Parkin, PhD FRCP
Organizational Affiliation
Mereo BioPharma
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85712
Country
United States
Facility Name
Novartis Investigative Site
City
San Diego
State/Province
California
ZIP/Postal Code
92120
Country
United States
Facility Name
Novartis Investigative Site
City
Miramar
State/Province
Florida
ZIP/Postal Code
33025
Country
United States
Facility Name
Novartis Investigative Site
City
West Valley City
State/Province
Utah
ZIP/Postal Code
84120
Country
United States
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3X 2H9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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Safety and Efficacy of BGS649 in Obese, Hypogonadotropic Hypogonadal Men

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