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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01200862
First received: September 10, 2010
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Obese Hypogonadotropic Hypogonadism
Drug: Investigational new drug company code: BGS649
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Part I: Percentage of patients achieving normal sex hormone (testosterone) levels [ Time Frame: At week 4 and 12 ] [ Designated as safety issue: No ]
  • Part 2: Change from baseline in Homeostatic model assessment of insulin resistance (HOMA-IR) at week 4 and 12 [ Time Frame: Baseline, Week 4 and Week 12 ] [ Designated as safety issue: No ]
  • Part 2: Change from baseline in quantitative insulin sensitivity check index (QUICKI) at week 4 and 12 [ Time Frame: Baseline, Week 4 and Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics of BGS649: area under the concentration-time curve from time zero to time 't' (AUC0-t) [ Time Frame: pre-dose and post dose at different time from day 1 through week 24 ] [ Designated as safety issue: No ]

    PK samples will be collected at the following timepoints:

    Day 1 pre-dose, 1 and 8 hours post-dose; Day 2 (24 hours post-dose); Day 4 (72 hours postdose); Week 2 pre-dose; Week 3 pre-dose; Week 4 pre-dose and 1 hour post-dose; Day 23 (24 hours post week 4 dose); Week 5 pre-dose; Week 7 pre-dose; Week 9 pre-dose; Week 11 pre-dose and 1 hour post-dose; Day 72 (24 hours post week 11 dose); Week 12; Week 18 and Week 24/end of study.


  • Pharmacokinetics of BGS649: area under the concentration-time curve during a dosing interval (τ) [AUCtau) [ Time Frame: pre-dose and post dose at different time from day 1 through week 24 ] [ Designated as safety issue: No ]
    PK samples will be collected at the following timepoints: Day 1 pre-dose, 1 and 8 hours post-dose; Day 2 (24 hours post-dose); Day 4 (72 hours postdose); Week 2 pre-dose; Week 3 pre-dose; Week 4 pre-dose and 1 hour post-dose; Day 23 (24 hours post week 4 dose); Week 5 pre-dose; Week 7 pre-dose; Week 9 pre-dose; Week 11 pre-dose and 1 hour post-dose; Day 72 (24 hours post week 11 dose); Week 12; Week 18 and Week 24/end of study.

  • Pharmacokinetics of BGS649: maximum (peak) observed blood drug concentration after single dose administration (Cmax) [ Time Frame: pre-dose and post dose at different time from day 1 through week 24 ] [ Designated as safety issue: No ]
    PK samples will be collected at the following timepoints: Day 1 pre-dose, 1 and 8 hours post-dose; Day 2 (24 hours post-dose); Day 4 (72 hours postdose); Week 2 pre-dose; Week 3 pre-dose; Week 4 pre-dose and 1 hour post-dose; Day 23 (24 hours post week 4 dose); Week 5 pre-dose; Week 7 pre-dose; Week 9 pre-dose; Week 11 pre-dose and 1 hour post-dose; Day 72 (24 hours post week 11 dose); Week 12; Week 18 and Week 24/end of study.

  • Pharmacokinetics of BGS649: Time to reach maximum (peak) blood drug concentration after single dose administration (Tmax) [ Time Frame: pre-dose and post dose at different time from day 1 through week 24 ] [ Designated as safety issue: No ]
    PK samples will be collected at the following timepoints: Day 1 pre-dose, 1 and 8 hours post-dose; Day 2 (24 hours post-dose); Day 4 (72 hours postdose); Week 2 pre-dose; Week 3 pre-dose; Week 4 pre-dose and 1 hour post-dose; Day 23 (24 hours post week 4 dose); Week 5 pre-dose; Week 7 pre-dose; Week 9 pre-dose; Week 11 pre-dose and 1 hour post-dose; Day 72 (24 hours post week 11 dose); Week 12; Week 18 and Week 24/end of study.

  • Pharmacokinetics of BGS649: elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve (T1/2) [ Time Frame: pre-dose and post dose at different time from day 1 through week 24 ] [ Designated as safety issue: No ]
    PK samples will be collected at the following timepoints: Day 1 pre-dose, 1 and 8 hours post-dose; Day 2 (24 hours post-dose); Day 4 (72 hours postdose); Week 2 pre-dose; Week 3 pre-dose; Week 4 pre-dose and 1 hour post-dose; Day 23 (24 hours post week 4 dose); Week 5 pre-dose; Week 7 pre-dose; Week 9 pre-dose; Week 11 pre-dose and 1 hour post-dose; Day 72 (24 hours post week 11 dose); Week 12; Week 18 and Week 24/end of study.

  • Assess the pharmacodynamic effect of BGS649 on glucose, insulin and lipid metabolism, and body composition [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Number of participants with adverse events to assess safety and tolerability of BGS649 in obese men [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 29
Study Start Date: August 2010
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BGS649 Drug: Investigational new drug company code: BGS649
Placebo Comparator: Placebo to BGS649 Drug: Placebo

  Eligibility

Ages Eligible for Study:   30 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01200862

Locations
United States, Arizona
Novartis Investigative Site
Tucson, Arizona, United States, 85712
United States, California
Novartis Investigative Site
San Diego, California, United States, 92120
United States, Florida
Novartis Investigative Site
Miramar, Florida, United States, 33025
United States, Utah
Novartis Investigative Site
West Valley City, Utah, United States, 84120
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3X 2H9
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01200862     History of Changes
Other Study ID Numbers: CBGS649A2204
Study First Received: September 10, 2010
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Novartis:
Obese
obesity
hypogonadism
hypogonadotropic
hyperestrogenemic
testosterone
hypogonadal

Additional relevant MeSH terms:
Obesity
Hypogonadism
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Gonadal Disorders
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 22, 2014