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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Placebo control; Drug: MOD-6031

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: OPKO Health, Inc.
• Collaborators: Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): December 15, 2016
• Study Completion (Actual): December 15, 2016

Study Registration Dates

• First Submitted: February 4, 2016
• First Submitted That Met QC Criteria: February 22, 2016
• First Posted (Estimate): February 26, 2016

Study Record Updates

• Last Update Posted (Actual): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Obesity
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: CP-6-001