Oral and IV Baclofen in Adult Volunteers

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Males and females between the ages of 18-65.
Subjects are capable of giving informed consent.
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.
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.

Exclusion Criteria

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

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

Arm && Interventions

Group	Intervention	Description
Oral Baclofen	Oral baclofen	-
Intervenous baclofen	Intervenous baclofen	Crossover study that eacg subject is given both oral and intervenous baclofen

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
assessment of sedation	up to 12 hours	Sedation will be measured using the Stanford Sleepiness Scale.
Ataxia	up to 12 hours after infusion	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.
Nystagmus	up to 12 hours following drug administration	Nystagmus will be measured using the following scale. 0=none, 1=mild, 2=severe mild-present on extreme gaze; severe-present on midline gaze
blood pressure	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.	diastolic and systolic blood pressure will be measured

Locations (1): University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States