Clinical trial NCT01749319: Oral and IV Baclofen in Adult Volunteers
Official title: Prevention of Baclofen Withdrawal Syndrome: Two-Way Crossover Study of Oral and Intravenous Baclofen in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Baclofen Withdrawal Syndrome
Keywords: baclofen, withdrawal, interuption, spasticity, pharmacokinetics, tolerability, intravenous, oral
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Paralyzed Veterans of America Research Foundation
First posted: 2012-12-13
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: oral bioavailability
timeFrame: 5, 15, 30 minutes, and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
timeFrame: 5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
measure: Plasma Decay Half-Life (t1/2)
timeFrame: 5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
measure: Maximum concentration (Cmax)
timeFrame: 5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
measure: Tmax
timeFrame: 5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration
Secondary outcomes:
measure: assessment of sedation
timeFrame: up to 12 hours
measure: Ataxia
timeFrame: up to 12 hours after infusion
measure: Nystagmus
timeFrame: up to 12 hours following drug administration
measure: blood pressure
timeFrame: 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.
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
References: