An Efficacy, Safety and Pharmacokinetics Study of Beloranib (ZGN-440 for Injectable Suspension) in Obese Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Zafgen, Inc.
ClinicalTrials.gov Identifier:
NCT01666691
First received: August 8, 2012
Last updated: May 21, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to evaluate weight reduction, safety and pharmacokinetics for certain doses of beloranib (ZGN-440 for injectable suspension) administered as twice-weekly subcutaneous injections for 12 weeks.


Condition Intervention Phase
Obesity
Drug: Beloranib
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo Controlled, Dose Ranging Phase 2 Trial of Beloranib (ZGN-440 for Injectable Suspension), A Novel Methionine Aminopeptidase 2 Inhibitor, in Obese Subjects to Evaluate Weight Reduction, Safety, and Pharmacokinetics Over 12 Weeks

Resource links provided by NLM:


Further study details as provided by Zafgen, Inc.:

Primary Outcome Measures:
  • Safety and tolerability of beloranib (ZGN-440 for injectable suspension) administered subcutaneously for 12 weeks [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: Yes ]
    Safety and tolerability of beloranib will be assessed by comparing frequency and severity of adverse events as well as changes in physical examinations, ECGs, vital signs and laboratory evaluations. Other safety oriented questionnaires and parameters (e.g. sleep quality, hemodynamic parameters) will be measured and evaluated.

  • Weight loss and responses in metabolic biomarkers over a dose range of ZGN-440 [ Time Frame: Up to 13 weeks ] [ Designated as safety issue: No ]
    Change from baseline in body weight and body composition (bioimpedance assessments), and scores of hunger/appetite over the dosing period will be evaluated to document beloranib's effect on obesity. Biomarkers of lipid metabolism will be measured to assess possible mechanisms of loss of body fat, as well as endocrinologic or anti-inflammatory markers.


Secondary Outcome Measures:
  • Pharmacodynamics over a dose range of beloranib [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    The plasma PK of beloranib and selected metabolites may be assessed following dose administration to compare systemic exposure and PK parameters over the range of doses. PK parameters include Cmax, Tmax, AUC24hour, AUC∞, volume of distribution, total clearance, terminal elimination constant, and half-life. Mean residence time may also be reported.

  • Compare the plasma pharmacokinetic profile of beloranib administered subcutaneously with the profiles obtained previously using an alternative formulation administered subcutaneously and with ZGN-433 (beloranib hemioxalate) administered intravenously [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Apparent bioavailability over a dose range of beloranib [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Bioavailability will be estimated from the SC PK parameters compared to the profile from comparable doses in earlier IV administration studies.


Enrollment: 160
Study Start Date: August 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
ZGN-440 sterile diluent
Drug: Placebo
Subjects will receive placebo twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses.
Other Name: ZGN-440 sterile diluent
Experimental: 0.3 mg Beloranib
0.3 mg ZGN-440 for injectable suspension
Drug: Beloranib
Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.
Other Names:
  • ZGN-440 for injectable suspension
  • ZGN-440
  • ZGN-433
  • Beloranib
Experimental: 0.6 mg Beloranib
0.6 mg ZGN-440 for injectable suspension
Drug: Beloranib
Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.
Other Names:
  • ZGN-440 for injectable suspension
  • ZGN-440
  • ZGN-433
  • Beloranib
Experimental: 1.2 mg Beloranib
1.2 mg ZGN-440 for injectable suspension
Drug: Beloranib
Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.
Other Names:
  • ZGN-440 for injectable suspension
  • ZGN-440
  • ZGN-433
  • Beloranib
Experimental: 2.4 mg Beloranib
2.4 mg ZGN-440 for injectable suspension
Drug: Beloranib
Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.
Other Names:
  • ZGN-440 for injectable suspension
  • ZGN-440
  • ZGN-433
  • Beloranib
Experimental: 3.2 mg Beloranib
3.2 mg ZGN-440 for injectable suspension
Drug: Beloranib
Subjects will receive ZGN-440 twice-weekly subcutaneous injections for up to 12 weeks and a total of 24 doses. A range of doses will be evaluated.
Other Names:
  • ZGN-440 for injectable suspension
  • ZGN-440
  • ZGN-433
  • Beloranib

Detailed Description:

This protocol is designed to test the safety and efficacy of a drug called beloranib (ZGN-440 for injectable suspension). It is to be tested for its ability to reduce weight in obese subjects. The study will provide information on how much ZGN-440 gets into the blood, how long it stays in the body, and how it affects other biological markers.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Obese volunteers weighing ≥ 50 kg
  • BMI ≥ 30 and ≤ 50 kg/m2
  • Stable body weight during the past 2 months
  • Type 2 diabetes mellitus is allowed

Exclusion Criteria:

  • Use of weight loss agents in the past month
  • Current, clinically significant eating disorder
  • Type 1 diabetes mellitus
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01666691

Locations
Australia, Queensland
Q-Pharm Clinics, Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia
Australia, South Australia
CMAX
Adelaide, South Australia, Australia, 5000
Australia, Western Australia
Linear Clinical Research Ltd
Perth, Western Australia, Australia, 6009
Sponsors and Collaborators
Zafgen, Inc.
Investigators
Principal Investigator: J K Marjason, MD Q-Pharm Clinics, Royal Brisbane and Women's Hospital
  More Information

No publications provided

Responsible Party: Zafgen, Inc.
ClinicalTrials.gov Identifier: NCT01666691     History of Changes
Other Study ID Numbers: ZAF-201
Study First Received: August 8, 2012
Last Updated: May 21, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee

Keywords provided by Zafgen, Inc.:
Obese
Obesity
Overweight
Weight loss
Weight reduction
Beloranib

Additional relevant MeSH terms:
Obesity
Weight Loss
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Body Weight Changes

ClinicalTrials.gov processed this record on April 14, 2014