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

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

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).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Arbaclofen placarbil 15 mg BID; Drug: Arbaclofen placarbil 30 mg BID; Drug: Arbaclofen placarbil 45 mg BID; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 228
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • XenoPort Clinical Site
    • Tucson, Arizona, United States, 85701
      • XenoPort Clinical Site
  • California
    • Berkeley, California, United States, 94705
      • XenoPort Clinical Site
    • San Diego, California, United States, 92103
      • XenoPort Clinical Site
  • Colorado
    • Denver, Colorado, United States, 80012
      • XenoPort Clinical Site
  • Florida
    • Port Charlotte, Florida, United States, 33948
      • XenoPort Clinical Site
    • Saint Petersburg, Florida, United States, 33701
      • XenoPort Clinical Site
    • Sarasota, Florida, United States, 34231
      • XenoPort Clinical Site
    • Tampa, Florida, United States, 33604
      • XenoPort Clinical Site
  • Illinois
    • Lake Barrington, Illinois, United States, 60010
      • XenoPort Clinical Site
  • Indiana
    • Indianapolis, Indiana, United States, 46204
      • XenoPort Clinical Site
  • Kansas
    • Lenexa, Kansas, United States, 66210
      • XenoPort Clinical Site
  • Kentucky
    • Lexington, Kentucky, United States, 40505
      • XenoPort Clinical Site
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • XenoPort Clinical Site
    • Detroit, Michigan, United States, 48202
      • XenoPort Clinical Site
  • New Jersey
    • Toms River, New Jersey, United States, 08753
      • XenoPort Clinical Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • XenoPort Clinical Site
  • New York
    • Albany, New York, United States, 12208
      • XenoPort Clinical Site
    • Patchogue, New York, United States, 11772
      • XenoPort Clinical Site
    • Plainview, New York, United States, 11803
      • XenoPort Clinical Site
  • North Carolina
    • Asheville, North Carolina, United States, 28805
      • XenoPort Clinical Site
  • Ohio
    • Akron, Ohio, United States, 44320
      • XenoPort Clinical Site
  • Tennessee
    • Franklin, Tennessee, United States, 37064
      • XenoPort Clinical Site
    • Nashville, Tennessee, United States, 37205
      • XenoPort Clinical Site
  • Texas
    • San Antonio, Texas, United States, 78206
      • XenoPort Clinical Site
  • Virginia
    • Vienna, Virginia, United States, 22181
      • XenoPort Clinical Site
  • Washington
    • Seattle, Washington, United States, 98108
      • XenoPort Clinical Site
    • Tacoma, Washington, United States, 98404
      • XenoPort Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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).
2. 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.
3. Expanded Disability Status Scale (EDSS) rating between 3.0-8.0 inclusive.
4. 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.
5. Spasticity Disability Rating of 2 or higher at Baseline.
6. 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:

1. Spasticity due to neurological disorder other than MS or other conditions that may confound the assessment of spasticity.
2. Subject has clinically evident muscle contractures resulting in irreversible spasticity in lower extremities.
3. 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
4. Botulinum toxin injection within 6 months of Screening or has current residual associated side effects at Screening.
5. Subjects receiving concomitant medication from more than one of the following three drug classes: (Antiepileptic drugs, Tricyclic anti-depressants and Opioids)

6. 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.
7. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: XenoPort, Inc.

Publications and helpful links

Helpful Links

• The Command Clinical Research Trial Website

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: May 22, 2011
• First Submitted That Met QC Criteria: May 23, 2011
• First Posted (Estimate): May 24, 2011

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; GABA Agents; Neuromuscular Agents; Muscle Relaxants, Central; GABA Agonists; GABA-B Receptor Agonists; Baclofen; Arbaclofen placarbil
• Other Study ID Numbers: XP-B-089

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO