Efficacy and Safety of Arbaclofen Placarbil in Subjects With Spasticity Due to Multiple Sclerosis

Study Overview
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Brief Summary
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To evaluate the efficacy of three doses of XP19986 (arbaclofen placarbil) compared to placebo for the treatment of spasticity in subjects with multiple sclerosis (MS).

Official Title
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A Randomized, Double Blind, Placebo-Controlled Efficacy and Safety Study of Arbaclofen Placarbil in Subjects With Spasticity Due to Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Arbaclofen placarbil 15 mg BID
* Drug: Placebo
* Drug: Arbaclofen placarbil 30 mg BID
* Drug: Arbaclofen placarbil 45 mg BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has multiple sclerosis (MS) based on Poser or McDonald Criteria (all subtypes of MS will be accepted, including relapsing remitting, primary or secondary progressive, if disease is stable per exclusion criteria). Maximum Ashworth Score Scale score of ≥ 2 in at least one of the following muscle groups on either side of the body: hip abductors/adductors, knee flexors/extensors, ankle flexors/extensors. Expanded Disability Status Scale (EDSS) rating between 3.0-8.0 inclusive. If a subject is on disease modifying MS treatment, the dosage, frequency, and route of administration must be stable for at least 30 days before screening and is expected to be stable throughout the study. Spasticity Disability Rating of 2 or higher at Baseline. Willing to discontinue and refrain from using for the duration of the study drugs for the treatment of spasticity or likely to affect spasticity (including, but not limited to, baclofen, tizanidine, diazepam, clonazepam, metaxalone, dantrolene, cyclobenzaprine, carisoprodol, clonidine, vigabatrin, valproic acid and cannabis). Exclusion Criteria: Spasticity due to neurological disorder other than MS or other conditions that may confound the assessment of spasticity. Subject has clinically evident muscle contractures resulting in irreversible spasticity in lower extremities. Subjects who have suffered an acute relapse of MS (as determined by the Investigator) within 90 days prior to Screening, or have had more than 1 relapse within the year prior to Screening Botulinum toxin injection within 6 months of Screening or has current residual associated side effects at Screening. Subjects receiving concomitant medication from more than one of the following three drug classes: (Antiepileptic drugs, Tricyclic anti-depressants and Opioids) Subjects on the following medications, at doses above the specified limits, are excluded if they cannot maintain a level within these limits Gabapentin ≤ 1800 mg per day or pregabalin ≤ 150 mg per day Amitriptyline ≤ 75 mg per day or nortriptyline ≤ 75 mg per day Opioids ≤ 30 mg morphine equivalents per day. Evidence of unstable or severe systemic illness, including but not limited to: Cardiovascular disease (e.g., chronic ventricular arrhythmia, unstable angina or CHF), respiratory disease (e.g., sleep apnea, COPD requiring oxygen therapy or hospitalization in last year), endocrine disease, hepatic disease (e.g., chronic active hepatitis), renal disease, or immunodeficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arbaclofen placarbil 15 mg BID<br>Arbaclofen placarbil (XP19986 SR4) 15 mg every morning and every evening | Drug: Arbaclofen placarbil 15 mg BID<br>* arbaclofen placarbil 15 mg BID<br>* Other names: XP19986 SR4;|
| Active Comparator: Arbaclofen placarbil 30 mg BID<br>Arbaclofen placarbil (XP19986 SR4) 30 mg every morning and every evening | Drug: Arbaclofen placarbil 30 mg BID<br>* arbaclofen placarbil 30 mg BID<br>* Other names: XP19986 SR4;|
| Active Comparator: Arbaclofen placarbil 45 mg BID<br>Arbaclofen placarbil (XP19986 SR4) 45 mg every morning and every evening | Drug: Arbaclofen placarbil 45 mg BID<br>* arbaclofen placarbil 45 mg BID<br>* Other names: XP19986 SR4;|
| Placebo Comparator: Placebo<br>Placebo every morning and every evening | Drug: Placebo<br>* Placebo for arbaclofen placarbil 15, 30 and 45 mg BID<br>* Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Maximum Ashworth Scale score (6 hour post-dose time point) | numerical score | 10-weeks | 
| Patient Global Impression of Change (PGIC) score | numerical score | 10-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the overall Modified PRISM score | Variables | Weeks 4, 6, 10 | 
| Change in weekly average severity of pain score associated with muscle spasm. | numerical score | Week 10 | 
| Change in weekly average VAS score of sleep quality | numerical score | Week 10 |