Effect of Methylnaltrexone (MNTX) on Electrocardiogram (ECG) Parameters and Cardiac Repolarization

A Randomized, Double-Blind, Placebo/Positive Controlled, Evaluation of the Effects of MNTX on ECG Parameters and Cardiac Repolarization in Normal Volunteers

This study will employ a single-center, randomized, double-blind parallel-group design for MNTX and placebo, with a positive control (moxifloxacin) dosed single-blind to confirm methodology, in normal healthy male and female volunteers. Multiple ECGs will be obtained after single clinical and supratherapeutic doses of MNTX to assess ECG effects compared to placebo.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: Methylnaltrexone (MNTX); Drug: Methylnaltrexone (MNTX); Drug: Methylnaltrexone (MNTX)

• Study Type: Interventional
• Enrollment (Actual): 546
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Tarrytown, New York, United States, 10591
      • Progenics Pharmaceuticals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy and free of acute active illnesses
2. Males and females between the ages of 18 and 45 years, inclusive
3. Body mass index between 18-30, inclusive, and weight between 50-110 kgs
4. ECG within normal limits (including PR <220, QRS <110, and QTc <450 ms.)

Exclusion Criteria:

1. Previous MNTX exposure
2. Currently pregnant or nursing
3. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, or other medically significant disorders
4. Consumption of alcoholic beverages within 7 days prior to study confinement
5. Any evidence of congenital or familial long-QT syndrome
6. History of drug abuse of positive findings on urine drug screen
7. Known allergy or hypersensitivity to MNTX or its excipients, moxifloxacin, opioids, or related drugs or a history or relevant adverse drug reactions of any origin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: Methylnaltrexone (MNTX); Dose 1; Drug: Methylnaltrexone (MNTX); Dose 2; Drug: Methylnaltrexone (MNTX); Dose 3
Experimental: Arm 2	Drug: Methylnaltrexone (MNTX); Dose 1; Drug: Methylnaltrexone (MNTX); Dose 2; Drug: Methylnaltrexone (MNTX); Dose 3
Experimental: Arm 3	Drug: Methylnaltrexone (MNTX); Dose 1; Drug: Methylnaltrexone (MNTX); Dose 2; Drug: Methylnaltrexone (MNTX); Dose 3
Placebo Comparator: Arm 4	Drug: Placebo
Active Comparator: Arm 5	Drug: Moxifloxacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of MNTX on QTcI duration	The primary objective of the study is to compare the effects of clinical and supratherapeutic doses of MNTX with the effects of placebo on QTcI duration in healthy volunteers.	3 days

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): February 1, 2005

Study Registration Dates

• First Submitted: May 27, 2011
• First Submitted That Met QC Criteria: May 27, 2011
• First Posted (Estimate): June 1, 2011

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Narcotic Antagonists; Alcohol Deterrents; Moxifloxacin; Naltrexone; Methylnaltrexone
• Other Study ID Numbers: MNTX 1106