Pharmacokinetics and Bioavailability of Single Subcutaneous Doses of Methylnaltrexone Versus Intravenous Dose

An Open-Label, Phase I Study of the Pharmacokinetics and Bioavailability of Single, Ascending Subcutaneous Doses of Methylnaltrexone Versus Intravenous Dose in Normal, Healthy Male Volunteers

This is an open-label, Phase I study. Study treatments will entail a four-way crossover among three single, ascending, subcutaneous doses and one intravenous dose of MNTX in six healthy normal male volunteers. Blood samples will be obtained to determine plasma pharmacokinetics, dose proportionality for subcutaneous doses, and absolute bioavailability versus an intravenous dose.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: SC Methylnaltrexone (MNTX); Drug: SC Methylnaltrexone (MNTX); Drug: SC Methylnaltrexone (MNTX); Drug: IV Methylnaltrexone (MNTX)

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subject weight between 60 and 80 kg
2. Subject a non-smoker
3. Subject in good physical health, based on history, physical exam, appropriate laboratory and diagnostics tests at screening with no evidence of clinically significant chronic medical condition.

Exclusion Criteria:

1. Subject with known hypersensitivity to methylnaltrexone, naltrexon or other opioids
2. Subject consuming any prescription medication within the past two weeks, over-the-counter (OTC) products within seven days, any experimental medication within 30 days prior to study screening, or of any drug with a half-life longer then three days within 10 half-lives (>30 days) of screening
3. Subject consuming barbiturates or other inducers or inhibitors of CYP450 within 3 months of screening
4. Subject with history or evidence of cardiovascular, gastrointestinal, hepatic, neurological, pulmonary, and renal or other significant chronic illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1	Drug: SC Methylnaltrexone (MNTX); Dose 1; Drug: SC Methylnaltrexone (MNTX); Dose 2; Drug: SC Methylnaltrexone (MNTX); Dose 3
EXPERIMENTAL: Arm 2	Drug: SC Methylnaltrexone (MNTX); Dose 1; Drug: SC Methylnaltrexone (MNTX); Dose 2; Drug: SC Methylnaltrexone (MNTX); Dose 3
EXPERIMENTAL: Arm 3	Drug: SC Methylnaltrexone (MNTX); Dose 1; Drug: SC Methylnaltrexone (MNTX); Dose 2; Drug: SC Methylnaltrexone (MNTX); Dose 3
EXPERIMENTAL: Arm 4	Drug: IV Methylnaltrexone (MNTX)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration of MNTX	The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.	32 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Maximum Plasma Concentration (Tmax) of MNTX	The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.	32 days
Clearance of MNTX	The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.	32 days
Half-live of MNTX	The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.	32 days
Volume of Distribution of MNTX	The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.	32 days
Area Under the Plasma Concentration versus Time Curve (AUC) of MNTX	The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.	32 days
Urinary Clearance of MNTX	The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.	32 days
Percentage of MNTX Excreted in Urine	The objective of this study is to determine the plasma pharmacokinetic of single, ascending, subcutaneous doses and a single intravenous dose of methylnaltrexone (MNTX) in normal healthy male subjects.	32 days

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2002
• Primary Completion (ACTUAL): August 1, 2002
• Study Completion (ACTUAL): August 1, 2002

Study Registration Dates

• First Submitted: May 27, 2011
• First Submitted That Met QC Criteria: June 6, 2011
• First Posted (ESTIMATE): June 7, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 27, 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; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone; Methylnaltrexone
• Other Study ID Numbers: MNTX 103