Safety Study of the Inhibition of Agouti-related Protein (AgRP) for the Management of Obesity and Weight Loss

A Prospective, Double-Blind, Randomized, Placebo-Controlled, Phase IIa, Multiple Dose, Multicenter Study to Assess Safety and Tolerability of TTP435 in Obese (Class 1-2) Subjects Over 8 Weeks of Treatment

Multiple pathways including peripheral and central hormones and neurotransmitters are involved in the regulation of food intake and body weight. One of the most studied pathways involves the melanocortin receptor. Agouti-related protein (AgRP) and alpha-melanocyte stimulating hormone (alphaMSH)have been shown to play an integral role in food intake and body weight.

It is reasonable to speculate that if there is an imbalance of alphaMSH and AgRP exist in obese individuals and inhibiting the activity of AgRP may be of therapeutic benefit in treating obesity.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: TTP435

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 5R3
  • Ontario
    • Oakville, Ontario, Canada, L6H 3P1
    • Toronto, Ontario, Canada
• United States
  • California
    • Los Angeles, California, United States, 90095
    • San Diego, California, United States, 92130
  • Georgia
    • Augusta, Georgia, United States, 30909
  • Illinois
    • Springfield, Illinois, United States, 26704
  • Nevada
    • Reno, Nevada, United States, 89502
  • New York
    • New York, New York, United States, 10065
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
  • Virginia
    • Norfolk, Virginia, United States, 23502
    • Richmond, Virginia, United States, 23294

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female volunteers, aged 18 to 65 years, inclusive.
• Subjects must be obese (class 1: BMI of 30.0 to 34.9 kg/m2 or class 2: BMI of 35 to 39.9 kg/m2 in non-Asians and BMI of 27.0 - 31.9 kg/m2 or 32.0 - 36.9 kg/m2 in Asians) at the Screening Visit.
• Female subjects must be postmenopausal (with amenorrhea for at least 2 years prior to scheduled dosing and confirmatory FSH test in the range of 23-116 IU/L) or surgically sterile (with physician or insurance documentation of bilateral tubal ligation at least 6 months prior to Screening Visit or of a hysterectomy and/or bilateral oophorectomy) and agree not to undergo in vitro fertilization during the study and for 6 months post treatment.

Exclusion Criteria:

• Type 1 diabetes.
• Type 2 diabetes.
• History of myocardial infarction, stroke, including transient ischemic attack, in the last 2 years.
• Asthma or chronic obstructive pulmonary disease controlled by regular use of inhaled steroids.
• Subjects with rheumatoid arthritis, lupus, or multiple sclerosis regularly requiring steroids or disease-modifying anti-rheumatic agents.
• Subjects with psoriasis requiring oral steroids.
• Subjects planning to undergo gastric bypass or resection surgery, or who have had such a procedure in the 6 months prior to the Screening Visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: TTP435	Drug: TTP435

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Participant Adverse Events	Day 1 to Day 70 (2 weeks post dose)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline Glucose Levels	Day 1 to Day 70 (2 weeks post dose)
Absolute Change in Body Weight	Day 1 to Day 70 (2 weeks post dose)
Absolute Change in Body Mass Index	Day 1 to Day 70 (2 weeks post dose)
Percent Change in Body Weight After 8 Weeks of Treatment with TTP435 or Placebo	Day 1 to Day 70 (2 weeks post dose)
Effect Subject-reported Satiety	Day 1 to Day 70 (2 weeks post dose)
Change from Baseline Insulin Levels	Day 1 to Day 70 (2 weeks post dose)
Change from Baseline Free Fatty Acid Levels	Day 1 to Day 70 (2 weeks post dose)
Change from Baseline Leptin Levels	Day 1 to Day 70 (2 weeks post dose)

Collaborators and Investigators

• Sponsor: vTv Therapeutics
• Investigators: Study Chair: James Wamsley, MD, vTv Therapeutics

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 23, 2008
• First Submitted That Met QC Criteria: October 23, 2008
• First Posted (Estimate): October 24, 2008

Study Record Updates

• Last Update Posted (Estimate): June 27, 2011
• Last Update Submitted That Met QC Criteria: June 8, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Obesity; Weight Loss; Class 1; Class 2; AgRP; TTP435; alphaMSH; Agouti-Related Protein; alpha-melanocyte stimulating hormone
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: TTP435-201