Dose Escalation Study of Intravenous Baclofen in Healthy Adult Volunteers
Dose Escalation Study of Intravenous Baclofen in Healthy Adult Volunteers
The objective of this study is to determine safety and characterize pharmacokinetics of
 higher doses of intravenous baclofen in healthy subjects.

 Thirty-six healthy adults received a single dose of PO baclofen (10mg, 15mg or 20mg) and a
 10-minute infusion of IV baclofen (7.5mg, 11.5mg or 15mg respectively) with a minimum 48-hour
 wash out period. Twelve subjects also received a 60-minute infusion of 15mg IV baclofen
 following an additional 48-hour wash out period.

 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.
This randomized, open-label, dose escalation, crossover study was conducted at a contract
 clinical research facility. Three single doses were evaluated using three cohorts (N=12 per
 cohort). Study doses were as follows: cohort 1 - 7.5mg IV and 10mg PO, cohort 2 - 11.5mg IV
 and 15mg PO, and cohort 3 - 15mg IV and 20mg PO. The IV baclofen doses for this trial were
 based on a 75% bioavailability observed in a previous low dose study.16 The oral formulation
 of the study drug used in this trial was 10mg baclofen tablet (Teva Pharmaceutical Industries
 Ltd.) and is commercially available. The intravenous formulation was 2mg/mL solution
 manufactured by Aptuit LLC. for this study. IV infusions were administered over 10 minutes.
 In addition, cohort 3 received 15mg over a 60-minute infusion. There was a minimum 48-hour
 washout period between doses. Initially, 3 subjects received study drug at a given dose,
 after assessing the safety and tolerance of baclofen the additional 9 subjects received study
 drug.
Inclusion Criteria:

 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 hormonal birth control, 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:

 1. Women who are pregnant.

 2. Women who are breastfeeding.

 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, other than hormonal birth
 control.

 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.

 10. Sleep deprivation (for example. working the night shift the evening prior to the
 study).