A Single-dose, Dose-escalation Study of a Long-acting MOD-6031 in Healthy Overweight or Obese Subjects

Study Overview
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Brief Summary
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MOD-6031 is a long-acting reversibly PEGylated oxyntomodulin (OXM) therapeutic. The active moiety is a gastrointestinal neuropeptide with a sequence identical to endogenous human OXM and is an agonist for both glucagon-like peptide-1 (GLP1) and glucagon (GCG) receptors. The peptide is a natural appetite suppressant, secreted by L-cells in the digestive system following food intake leading to a decrease in gastric emptying, satiety after crossing the blood-brain barrier, and regulation of insulin and glucose levels. Thus, MOD-6031 is being developed as a treatment for high risk subjects (obese) to increase weight loss, reduce food intake and increase glycemic control.

Detailed Description
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This will be a a randomized, single-blind, placebo-controlled, single-dose, dose-escalation study. Five escalating dose groups are planned, with 8 subjects per dose group, randomized in 3:1 ratio to receive a single dose of MOD-6031 or matching Placebo (6 MOD-6031 to 2 placebo subjects). The initial MOD-6031 dose will be 20 mg, followed by single doses of 50 mg, 100 mg, 150 mg and 200 mg. Each subject will receive a single study drug injection in the morning (dosing day designated as Day 0) and will be monitored for 30 days.

Official Title
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A Phase I, Randomized, Single-Blinded, Placebo-Controlled, Single-Dose, Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of MOD-6031 in Healthy Volunteers

Conditions
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Obesity

Intervention / Treatment
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* Drug: MOD-6031
* Other: Placebo control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male, between 18 to 55 years of age. BMI 27-35 Kg/m2 (inclusive). Generally good health. Triglyceride ≤ 400mg/ml ECG with no clinically significant abnormalities. Negative HIV, hepatitis B or hepatitis C serology tests at screening No significant abnormalities in clinical laboratory parameters No history of alcohol or drug abuse. Exclusion Criteria: History of clinically significant medical condition. Any cardiac conduction defect. Any acute or unstable disease. History of malignancy diagnosed within the past 5 years. Known or suspected diabetes and/or HbA1C >6.4% on screening. Known allergy to any drug. Treatment with weight loss drugs (within 3 months prior to dosing). Liposuction or other surgery for weight loss within the last year. Evidence of eating disorders (bulimia, binge eating). History of regular alcohol consumption exceeding. Use of tobacco or nicotine-containing products. Subjects that have difficulty fasting or consuming the standard meals that will be provided.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Cohort 1<br>20mg MOD-6031 / Placebo | Drug: MOD-6031<br> <br> Other: Placebo control<br> <br> |
| Experimental: Dose Cohort 2<br>50mg MOD-6031 / Placebo | Drug: MOD-6031<br> <br> Other: Placebo control<br> <br> |
| Experimental: Dose Cohort 3<br>100mg MOD-6031 / Placebo | Drug: MOD-6031<br> <br> Other: Placebo control<br> <br> |
| Experimental: Dose Cohort 4<br>150mg MOD-6031 / Placebo | Drug: MOD-6031<br> <br> Other: Placebo control<br> <br> |
| Experimental: Dose Cohort 5<br>200mg MOD-6031 / Placebo | Drug: MOD-6031<br> <br> Other: Placebo control<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite safety and tolerability parameters as measured by adverse events, electrocardiograms (ECG), laboratory results, vital signs and injection site reactions |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of MOD-6031 and its hydrolyzed derivatives (PEG-FMS and OXM peptide) |  | 0 to 30 days | 
| Tmax of MOD-6031 and its hydrolyzed derivatives (PEG-FMS and OXM peptide) |  | 0 to 30 days | 
| AUC(0-t) of MOD-6031 and its hydrolyzed derivatives (PEG-FMS and OXM peptide) |  | 0 to 30 days | 
| AUC(inf) of MOD-6031 and its hydrolyzed derivatives (PEG-FMS and OXM peptide) |  | 0 to 30 days | 
| Elimination rate constant of MOD-6031 and its hydrolyzed derivatives (PEG-FMS and OXM peptide) |  | 0 to 30 days | 
| T(½) of MOD-6031 and its hydrolyzed derivatives (PEG-FMS and OXM peptide) |  | 0 to 30 days | 
| CL/F of MOD-6031 and its hydrolyzed derivatives (PEG-FMS and OXM peptide) |  | 0 to 30 days | 
| Vz/F of MOD-6031 and its hydrolyzed derivatives (PEG-FMS and OXM peptide) |  | 0 to 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity