Pharmacokinetic and Bioequivalence Comparison of Baclofen and Chlorzoxazone Administered Individually or Concurrently

NCT05257447 | Completed Phase 1 FDA Drug

• 1 other identifier: STU2021-0797
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Combination treatment with baclofen and chlorzoxazone (CHZ) is under investigation for the treatment of spinocerebellar ataxia types 1 and 2. Achievement of therapeutic benefit with this combination approach requires that effective concentrations of both agents reach the systemic circulation, and ultimately reach the intended pharmacologic target. This in turn requires understanding of the clinical pharmacokinetic properties of both drugs when administered individually, as well as knowledge of the extent to which the agents might interact when given concurrently. Study Objectives:

1. 1.To evaluate the pharmacokinetic properties of baclofen and CHZ when administered as individual entities at separate times, using customary clinical doses.
2. 2.To compare the pharmacokinetic properties, and assess the bioequivalence, of each drug administered separately compared to administration of the two drugs concurrently.
3. 3.To assess adverse events attributed to the two drugs when administered separately or together.

Conditions

Pharmacokinetics

Keywords

baclofen; chlorzoxazone; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Comparison of the maximum measured plasma concentration (Cmax) of baclofen or chlorzoxazone administered separately with baclofen-chlorzoxazone administered concurrently.

  Compare the pharmacokinetic properties and assess bioequivalence of baclofen and chlorzoxazone administered separately compared to baclofen-chlorzoxazone administered concurrently, determined by liquid chromatography-mass spectrometry. Maximum measured plasma concentration (Cmax) will be reported.

  Pre-dose and 1, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose

• Compare the area Under the Plasma Concentration Versus Time Curve (AUC) of baclofen and chlorzoxazone administered separately with baclofen-chlorzoxazone administered concurrently.

  Evaluate the pharmacokinetic properties of baclofen and chlorzoxazone administered individually, determined by liquid chromatography-mass spectrometry with baclofen-chlorzoxazone administered concurrently. Area under the plasma concentration curve until the last non-zero concentration (AUC-last) will be reported.

  Pre-dose and 1, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose

Other Outcomes (1)

• Number of adverse events reported as mild, moderate, or severe

  Visit 1 Day 1, Visit 1 Day 2, Visit 2 Day 1, Visit 2 Day 2, Visit 3, Day 1, Visit 3 Day 2

Study Arms (3)

Baclofen 20mg tablet

EXPERIMENTAL

Single oral dose of baclofen, 20 mg

Drug: Baclofen 20 mg Tablet

Chlorzoxazone 500mg tablet

EXPERIMENTAL

Single oral dose of chlorzoxazone, 500 mg

Drug: Chlorzoxazone 500 mg Tablet

Baclofen 20 mg tablet and chlorzoxazone 500 mg tablet

EXPERIMENTAL

Concurrent doses of baclofen, 20 mg, and chlorzoxazone, 500 mg

Drug: Baclofen 20mg tablet and Chlorzoxazone 500 mg tablet

Interventions

Baclofen 20 mg Tablet DRUG

Single oral dose given at approximately 8 AM on day of visit, with 6-8 ounces of tap water.

Baclofen 20mg tablet

Chlorzoxazone 500 mg Tablet DRUG

Single oral dose given at approximately 8 AM on day of visit, with 6-8 ounces of tap water.

Chlorzoxazone 500mg tablet

Baclofen 20mg tablet and Chlorzoxazone 500 mg tablet DRUG

Concurrent single oral dose given at approximately 8 AM on day of visit, with 6-8 ounces of tap water.

Baclofen 20 mg tablet and chlorzoxazone 500 mg tablet

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female
• Ages 18 to 55 years of age
• Ambulatory
• Non-smoker
• No current or past history of significant medical or psychiatric disease
• Not currently taking prescription medications or on a regular or recurrent basis

You may not qualify if:

• Non-ambulatory
• Smokers
• Current or past history of significant medical or psychiatric disease
• Currently taking prescription medications or taking on a regular or recurrent basis
• Available information about potential participant indicates that participation would not be safe or appropriate, per PI discretion

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Tufts University: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (18)

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MeSH Terms

Interventions

Baclofen; Tablets; Chlorzoxazone

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Benzoxazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Vikram Shakkottai, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology, Dedman Family Distinguished Chair in Neurological Disease, Vice Chair for Basic Science Research

Model Details: The study will have a randomized, single-dose, 3-way crossover design, with at least one week elapsing between the 3 trials of the study. The sequence of administration is based on a randomization code.

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: February 25, 2022
• Study Start: April 27, 2022
• Primary Completion: December 13, 2022
• Study Completion: December 13, 2022
• Last Updated: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Researchers who provide a methodologically sound proposal should direct inquiries to vikram.shakkottai@utsouthwestern.edu. Data requestors may need to sign a data access agreement.

Locations

US (1)