Repeated Dose IV Baclofen Safety/Bioequivalence Study

Allaysis, LLC42 enrolled

Overview

The purpose of this study is to identify a suitable dosing regimen of IV baclofen to serve as a temporary substitute for an oral regimen.

Baclofen intravenous solution 2 mg/mL will be manufactured and provided by Allaysis, LLC. Prism Clinical Research will purchase oral baclofen tablets (10 mg) from a commercial supplier. Subject will start baclofen at a 5 mg oral dose every 8 hours. Oral baclofen will be increased incrementally and self-administered over 13 days to a maximum dose of 20 mg every 8 hours. Subjects will be crossed over to 16 mg intravenous baclofen infused over 120 (n=6) or 150 (n=6) minutes every 8 hours for 11 doses. Subjects will be changed back to oral baclofen at a 15 mg dose self-administered every 8 hours and tapered off of baclofen over 15 days. Following the completion of this group of 12 subjects, the remaining 30 subjects will receive IV baclofen at the infusion duration that best meets the criteria for bioequivalence.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Intravenous Baclofen

Interventions

IV BaclofenDRUG

Baclofen intravenous solution 2 mg/mL manufactured and provided by Allaysis, LLC

Oral BaclofenDRUG

10 mg tablet

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Males and females between the ages of 18-45. An attempt will be made to recruit an equal number of men and women into each dosing group; however a ratio of 2:4 in the initial run-in phase and 12:18, with either women or men in the majority is acceptable. * Subjects are capable of giving informed consent. * Females capable of bearing children should practice at least one or more of the following methods of contraception for at least one month prior to the and during the study: hormonal, intrauterine device (IUD), or barrier method in combination with a spermicide. Female subjects who are postmenopausal (no menses for greater than one year) or surgically incapable of bearing children may participate. * Subject should be medication free, other than hormonal birth control, for 48 hours before through 24 hours after completion of 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: * Women who are pregnant. * Women who are breastfeeding. * 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, other than hormonal birth control within 48 hours prior to baclofen administration, unless approved by the Principal Investigator. * 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.

Outcomes

Primary Outcomes

Bioequivalence of IV Baclofen Relative to Oral at Steady State

Evaluate and confirm selected infusion rates of IV baclofen which best achieve bioequivalence to oral baclofen at steady state in healthy adults.

Time frame: 2 dosing intervals (total of 16 hours)

Secondary Outcomes

Number of participants experiencing sedation due to the treatment measured by the sanford sleepiness scale

Over the course of the intervention (\~3 months) subjects will be assessed using the Modified Sanford sleepiness scale prior to the first and second intravenous drug administration then every 30 minutes for four hours after drug administration. If this assessment shows that the subject is not at their baseline, assessments will continue every 30 minutes until the subject has returned to the baseline function.

Time frame: 3 months

Number of participants experiencing nystagmus due to the treatment.

Over the course of the intervention (\~3 months) subjects will be assessed using the following rating scale and definitions of ataxia and nystagmus prior to the first and second intravenous drug administrations then every 30 minutes for four hours after drug administration. If this assessment shows that the subject is not at their baseline, assessments will continue every 30 minutes until the subject has returned to the baseline function. Nystagmus: 0 = None 1. mild - present only on extreme gaze (beyond 45 degrees lateral gaze) 2. severe - present on neutral to 45 degrees lateral gaze

Time frame: 3 months

Number of participants experiencing ataxia due to the treatment measured by tandem gait

Over the course of the intervention (\~3 months) subjects will be assessed using the following rating scale and definitions of ataxia and nystagmus prior to the first and second intravenous drug administrations then every 30 minutes for four hours after drug administration. If this assessment shows that the subject is not at their baseline, assessments will continue every 30 minutes until the subject has returned to the baseline function. Ataxia: For those who are ambulatory, this will be assessed by gait. Ratings will be: 0=none 1. Mild - unsteady with tandem gait testing, but able to perform without assistance 2. Severe - unable to perform gait testing without assistance. For non-ambulatory subjects, ataxia will be assessed by finger to nose and finger pursuit maneuvers.

Data from ClinicalTrials.gov

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