Oral and IV Baclofen in Adult Volunteers

Prevention of Baclofen Withdrawal Syndrome: Two-Way Crossover Study of Oral and Intravenous Baclofen in Healthy Adult Volunteers

The primary objective of this study is to characterize baclofen pharmacokinetics following oral and intravenous administration in patients who are on chronic oral baclofen therapy. The secondary objective is to determine the safety profile of an IV baclofen formulation.

This study is a randomized crossover study with two treatment arms. All subjects will receive a dose of oral baclofen and a dose of IV baclofen on separate study days. Whether the oral or intravenous form is given on the first study day will be randomized in a 1:1 manner.

The pharmacokinetic and tolerability information gained from this study will support the development of further studies to assess the use of IV baclofen to prevent or treat baclofen withdrawal syndrome.

Study Overview

• Status: Completed
• Conditions: Baclofen Withdrawal Syndrome
• Intervention / Treatment: Drug: Oral baclofen; Drug: Intervenous baclofen

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects will be eligible to participate in the study if all of the following conditions exist:

1. Males and females between the ages of 18-65.
2. Subjects are capable of giving informed consent.
3. Female subjects must be post-menopausal for at least 1 year, or surgically incapable of bearing children, or practicing at least one or more of the following methods of contraception for three months prior to, and during the study: hormonal, intrauterine device (IUD), or barrier method in combination with a spermicide.

4. Subject should be medication free, other than study drug, for 48 hours before through 24 hours after study drug administration. If the need for medication is identified during this time period, it will be discussed with and approved by the PI.

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Exclusion Criteria:

Subjects will be excluded from participation in the study if any of the following conditions exist:

1. Women who are pregnant.
2. Women who are breast feeding.
3. Subject has a history of intolerance to IV administration of medication.
4. Subject has a known hypersensitivity to baclofen.
5. Subject has a significant history of cardiac, neurologic, psychiatric, oncologic, endocrine, metabolic, renal or hepatic disease
6. Subject has taken or used any investigational drug or device in the 30 days prior to screening.
7. Subject has taken either prescribed or over the counter medication for 48 hours prior to baclofen administration on either of the study days.
8. Subject reveals clinically significant abnormalities on screening laboratory tests.
9. Subject is a non-English speaker, such that ability to ascertain neurological status would require an interpreter.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Baclofen	Drug: Oral baclofen; Each subject will receive one dose of oral baclofen and one dose of intravenous baclofen on different study days.
Experimental: Intervenous baclofen; Crossover study that eacg subject is given both oral and intervenous baclofen	Drug: Intervenous baclofen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
oral bioavailability	oral bioavailability is the fraction of an administered dose of unchanged drug that reaches the systemic circulation	5, 15, 30 minutes, and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]	AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).	5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
Maximum concentration (Cmax)	The maximum concentration is the maximum baclofen concentration observed	5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
Tmax	Tmax is the time at which the maximum baclofen concentration was observed	5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
assessment of sedation	Sedation will be measured using the Stanford Sleepiness Scale.	up to 12 hours
Ataxia	A rating scale of ataxia will be used: 0=none, 1=mild, 2=severe For those who are ambulatory, this will be assessed by gait. Ratings will be: mild-unsteady with tandem gait testing, but able to perform without assistance severe-unable to perform tandem gait testing without assistance. For non-ambulatory subjects, ataxia will be assessed by finger to nose and finger pursuit maneuvers.	up to 12 hours after infusion
Nystagmus	Nystagmus will be measured using the following scale. 0=none, 1=mild, 2=severe mild-present on extreme gaze; severe-present on midline gaze	up to 12 hours following drug administration
blood pressure	diastolic and systolic blood pressure will be measured	5 minutes immediately prior to, and during the IV infusion and oral administration, then every 15 minutes for 1 hour, then every hour for 12 hours.

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Paralyzed Veterans of America Research Foundation

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: December 11, 2012
• First Posted (Estimate): December 13, 2012

Study Record Updates

• Last Update Posted (Estimate): August 5, 2014
• Last Update Submitted That Met QC Criteria: August 4, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: baclofen, withdrawal, interuption, spasticity, pharmacokinetics, tolerability, intravenous, oral
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Syndrome; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; GABA Agents; Neuromuscular Agents; Muscle Relaxants, Central; GABA Agonists; GABA-B Receptor Agonists; Baclofen
• Other Study ID Numbers: CTSI 20873