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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Obesity

Intervention / Treatment
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* Drug: TTP435
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Experimental: TTP435<br> | Drug: TTP435<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Class 1, Class 2, Weight Loss, AgRP, TTP435, alphaMSH, Agouti-Related Protein, alpha-melanocyte stimulating hormone