Efficacy Study of Arbaclofen to Treat Spasticity in Multiple Sclerosis

A Randomized, Double-Blind, Parallel Group Study to Compare the Safety and Efficacy Arbaclofen ER Tablets to Placebo and Baclofen Tablets, USP for the Treatment of Spasticity in Patients With Multiple Sclerosis

This is a multicenter, randomized (1:1:1), double-blind, active and placebo controlled, parallel group study to evaluate safety, tolerability and efficacy of oral arbaclofen in MS patients with spasticity.

Eligible subjects will be removed from anti-spasticity medications for at least one week and then begin study drug treatment with daily doses increasing up to the target dose which will then be maintained for at least 12 weeks. A down-titration will then occur over two weeks.

This is a multicenter, randomized (1:1:1), double-blind, active and placebo controlled, parallel group study to evaluate safety, tolerability and efficacy of oral arbaclofen in MS patients with spasticity.

Eligible subjects will be removed from anti-spasticity medications for at least one week and then begin study drug treatment with daily doses increasing up to the target dose which will then be maintained for at least 12 weeks. A down-titration will then occur over two weeks with the final study visit occurring at 19 weeks from start of achieving the target dose or 22 weeks from the Study Visit 1.

Inclusion Criteria:

• Patients (male or female) 18 to 65 years of age, inclusive, at the time of dosing
• Have an established diagnosis (per McDonald Criteria) of Multiple Sclerosis (either relapsing remitting or secondary progressive course), that manifests spasticity for at least 6 months
• Spasticity due to MS as shown by a TNmAS score equal or greater than six (≥6) in the most affected limb.
• EDSS equal or greater than 3.0
• If receiving disease-modifying medications, these must have been at a stable dose for at least three (3) months prior to screening, and the subject must be willing to maintain this treatment for the duration of the study
• Stable regimen for at least thirty (30) days prior to study entry for all medications and non-pharmacological therapies that are intended to alleviate spasticity
• Absence of infections, peripheral vascular disease, painful contractures, advanced arthritis, or other conditions that hinder evaluation of joint movement
• Have a creatinine clearance, as calculated by Glomerular Filtration Rate using the Modification of Diet in Renal Disease (MDRD) Study equation, greater than 60mL/min.
• Use of a medically highly effective of birth control during the study and for ninety (90) days thereafter for women of child-bearing potential (including female subjects and female partners of non-sterile male subjects)
• Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of participation in the study

Exclusion Criteria:

• Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity
• Inability to rate their level of spasticity or distinguish it from other MS symptoms
• Acute MS exacerbation requiring treatment within twelve (12) weeks of screening
• Use of intravenous methylprednisolone within the twelve (12) weeks before visit 1
• Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables
• Use of botulinum toxin A or B within six (6) months of visit 1
• History of allergy to baclofen or any inactive component of test or reference formulation
• Pregnancy, lactation or planned pregnancy during the course of the study and for three (3) months thereafter.
• History of unstable psychiatric disease, or current signs and symptoms of significant medical disorders such as severe, progressive, or uncontrolled pulmonary, cardiac, gastrointestinal, hepatic, renal, genitourinary, hematological, endocrine, immunologic, or neurological disease
• History of seizures
• Current significant cognitive deficit, severe or untreated anxiety, severe or untreated depression
• Subjects with abnormal micturition that requires indwelling or intermittent catheterization or with lower urinary tract symptoms (LUTS) that result in a score greater than twenty-six (>26) in the Baseline USP© questionnaire
• Current malignancy or history of malignancy that has not been in remission for more than five (5) years, except effectively treated basal cell skin carcinoma
• Any other significant disease, disorder or significant laboratory finding which, in the opinion of the investigator, put the subject at risk because of participation, influence the result of the study, or affect the subject's ability to participate
• Planned elective surgery or other procedures requiring general anesthesia during the study
• Subject who is inappropriate for placebo medication in the judgment of the Investigator
• History of substance abuse within the past twelve (12) months
• Current chronic use of long acting opioids or round the clock use of short acting opioids for the treatment of pain
• Participation in another research study within thirty (30) days of Screening
• Patients who are uncooperative or unwilling to sign consent form