Oral and IV Baclofen in Adult Volunteers

This study is not yet open for participant recruitment.
Verified December 2012 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborator:
Paralyzed Veterans of America Research Foundation
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01749319
First received: December 4, 2012
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Baclofen Withdrawal Syndrome
Drug: Oral baclofen
Drug: Intervenous baclofen
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prevention of Baclofen Withdrawal Syndrome: Two-Way Crossover Study of Oral and Intravenous Baclofen in Healthy Adult Volunteers

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • oral bioavailability [ Time Frame: 5, 15, 30 minutes, and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration ] [ Designated as safety issue: No ]
    oral bioavailability is the fraction of an administered dose of unchanged drug that reaches the systemic circulation

  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] [ Time Frame: 5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration ] [ Designated as safety issue: No ]
    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 - ∞).

  • Plasma Decay Half-Life (t1/2) [ Time Frame: 5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Maximum concentration (Cmax) [ Time Frame: 5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration ] [ Designated as safety issue: No ]
    The maximum concentration is the maximum baclofen concentration observed

  • Tmax [ Time Frame: 5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration ] [ Designated as safety issue: No ]
    Tmax is the time at which the maximum baclofen concentration was observed


Secondary Outcome Measures:
  • assessment of sedation [ Time Frame: up to 12 hours ] [ Designated as safety issue: Yes ]
    Sedation will be measured using the Stanford Sleepiness Scale.

  • Ataxia [ Time Frame: up to 12 hours after infusion ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: up to 12 hours following drug administration ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    diastolic and systolic blood pressure will be measured


Estimated Enrollment: 12
Study Start Date: January 2013
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

    -

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01749319

Locations
United States, Minnesota
University of Minnesota Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Principal Investigator: Linda E Krach, MD         
Sub-Investigator: Robert L Kriel, MD         
Sub-Investigator: James C Cloyd, PharmD         
Sub-Investigator: Lisa D Coles, PhD         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Paralyzed Veterans of America Research Foundation
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01749319     History of Changes
Other Study ID Numbers: CTSI 20873
Study First Received: December 4, 2012
Last Updated: December 11, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
baclofen, withdrawal, interuption, spasticity, pharmacokinetics, tolerability, intravenous, oral

Additional relevant MeSH terms:
Substance Withdrawal Syndrome
Substance-Related Disorders
Mental Disorders
Baclofen
GABA-B Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Muscle Relaxants, Central
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014