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Oral and IV Baclofen in Adult Volunteers

Primary Purpose

Baclofen Withdrawal Syndrome

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Oral baclofen

Intervenous baclofen

About this trial

This is an interventional treatment trial for Baclofen Withdrawal Syndrome focused on measuring baclofen, withdrawal, interuption, spasticity, pharmacokinetics, tolerability, intravenous, oral

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

University of Minnesota

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Oral Baclofen

Intervenous baclofen

Arm Description

Crossover study that eacg subject is given both oral and intervenous baclofen

Outcomes

Primary Outcome Measures

oral bioavailability

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 - ∞)]

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)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Maximum concentration (Cmax)

The maximum concentration is the maximum baclofen concentration observed

Tmax

Tmax is the time at which the maximum baclofen concentration was observed

Secondary Outcome Measures

assessment of sedation

Sedation will be measured using the Stanford Sleepiness Scale.

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.

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

blood pressure

diastolic and systolic blood pressure will be measured

Full Information

NCT ID

NCT01749319

First Posted

December 4, 2012

Last Updated

August 4, 2014

Sponsor

University of Minnesota

Collaborators

Paralyzed Veterans of America Research Foundation

1. Study Identification

Unique Protocol Identification Number

NCT01749319

Brief Title

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

2. Study Status

Record Verification Date

August 2014

Overall Recruitment Status

Completed

Study Start Date

January 2013 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Minnesota

Collaborators

Paralyzed Veterans of America Research Foundation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Baclofen Withdrawal Syndrome

Keywords

baclofen, withdrawal, interuption, spasticity, pharmacokinetics, tolerability, intravenous, oral

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Oral Baclofen

Arm Type

Active Comparator

Arm Title

Intervenous baclofen

Arm Type

Experimental

Arm Description

Crossover study that eacg subject is given both oral and intervenous baclofen

Intervention Type

Drug

Intervention Name(s)

Oral baclofen

Intervention Description

Each subject will receive one dose of oral baclofen and one dose of intravenous baclofen on different study days.

Intervention Type

Drug

Intervention Name(s)

Intervenous baclofen

Primary Outcome Measure Information:

Title

oral bioavailability

Description

oral bioavailability is the fraction of an administered dose of unchanged drug that reaches the systemic circulation

Time Frame

5, 15, 30 minutes, and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration

Title

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]

Description

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 - ∞).

Time Frame

5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration

Title

Plasma Decay Half-Life (t1/2)

Description

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Time Frame

5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration

Title

Maximum concentration (Cmax)

Description

The maximum concentration is the maximum baclofen concentration observed

Time Frame

5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration

Title

Tmax

Description

Tmax is the time at which the maximum baclofen concentration was observed

Time Frame

5, 15, 30 min and 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration

Secondary Outcome Measure Information:

Title

assessment of sedation

Description

Sedation will be measured using the Stanford Sleepiness Scale.

Time Frame

up to 12 hours

Title

Ataxia

Description

Time Frame

up to 12 hours after infusion

Title

Nystagmus

Description

Nystagmus will be measured using the following scale. 0=none, 1=mild, 2=severe mild-present on extreme gaze; severe-present on midline gaze

Time Frame

up to 12 hours following drug administration

Title

blood pressure

Description

diastolic and systolic blood pressure will be measured

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

12. IPD Sharing Statement

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Oral and IV Baclofen in Adult Volunteers

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