Oral and IV Baclofen in 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.
Baclofen Withdrawal Syndrome
Drug: Oral baclofen
Drug: Intervenous baclofen
|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|
- 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
- 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
|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)|
|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|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01749319
|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|