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

• ClinicalTrials.gov Identifier: NCT01359566
• Recruitment Status: Completed
• First Posted: May 24, 2011
• Last Update Posted: February 21, 2021
• Sponsor: XenoPort, Inc.
• Information provided by (Responsible Party): XenoPort, Inc.

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: Arbaclofen placarbil 15 mg BID; Drug: Placebo; Drug: Arbaclofen placarbil 30 mg BID; Drug: Arbaclofen placarbil 45 mg BID	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 228 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo-Controlled Efficacy and Safety Study of Arbaclofen Placarbil in Subjects With Spasticity Due to Multiple Sclerosis
• Study Start Date: May 2011
• Actual Primary Completion Date: February 2013
• Actual Study Completion Date: February 2013

Arms and Interventions

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 Name: 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 Name: 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 Name: XP19986 SR4
Placebo Comparator: Placebo; Placebo every morning and every evening	Drug: Placebo; Placebo for arbaclofen placarbil 15, 30 and 45 mg BID; Other Name: Sugar Pill

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in Maximum Ashworth Scale score (6 hour post-dose time point) [ Time Frame: 10-weeks ]
   numerical score
2. Patient Global Impression of Change (PGIC) score [ Time Frame: 10-weeks ]
   numerical score

Secondary Outcome Measures :

1. Change in the overall Modified PRISM score [ Time Frame: Weeks 4, 6, 10 ]
   Variables
2. Change in weekly average severity of pain score associated with muscle spasm. [ Time Frame: Week 10 ]
   numerical score
3. Change in weekly average VAS score of sleep quality [ Time Frame: Week 10 ]
   numerical score

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

XenoPort Clinical Site

Phoenix, Arizona, United States, 85004

XenoPort Clinical Site

Tucson, Arizona, United States, 85701

United States, California

XenoPort Clinical Site

Berkeley, California, United States, 94705

XenoPort Clinical Site

San Diego, California, United States, 92103

United States, Colorado

XenoPort Clinical Site

Denver, Colorado, United States, 80012

United States, Florida

XenoPort Clinical Site

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

United States, Illinois

XenoPort Clinical Site

Lake Barrington, Illinois, United States, 60010

United States, Indiana

XenoPort Clinical Site

Indianapolis, Indiana, United States, 46204

United States, Kansas

XenoPort Clinical Site

Lenexa, Kansas, United States, 66210

United States, Kentucky

XenoPort Clinical Site

Lexington, Kentucky, United States, 40505

United States, Michigan

XenoPort Clinical Site

Bingham Farms, Michigan, United States, 48025

XenoPort Clinical Site

Detroit, Michigan, United States, 48202

United States, New Jersey

XenoPort Clinical Site

Toms River, New Jersey, United States, 08753

United States, New Mexico

XenoPort Clinical Site

Albuquerque, New Mexico, United States, 87102

United States, New York

XenoPort Clinical Site

Albany, New York, United States, 12208

XenoPort Clinical Site

Patchogue, New York, United States, 11772

XenoPort Clinical Site

Plainview, New York, United States, 11803

United States, North Carolina

XenoPort Clinical Site

Asheville, North Carolina, United States, 28805

United States, Ohio

XenoPort Clinical Site

Akron, Ohio, United States, 44320

United States, Tennessee

XenoPort Clinical Site

Franklin, Tennessee, United States, 37064

XenoPort Clinical Site

Nashville, Tennessee, United States, 37205

United States, Texas

XenoPort Clinical Site

San Antonio, Texas, United States, 78206

United States, Virginia

XenoPort Clinical Site

Vienna, Virginia, United States, 22181

United States, Washington

XenoPort Clinical Site

Seattle, Washington, United States, 98108

XenoPort Clinical Site

Tacoma, Washington, United States, 98404

Sponsors and Collaborators

XenoPort, Inc.

Investigators

• Study Director: Study Director; Indivior Inc.

More Information

Additional Information:

The Command Clinical Research Trial Website 

• Responsible Party: XenoPort, Inc.
• ClinicalTrials.gov Identifier: NCT01359566
• Obsolete Identifiers: NCT01360489
• Other Study ID Numbers: XP-B-089
• First Posted: May 24, 2011
• Last Update Posted: February 21, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Arbaclofen placarbil; Baclofen; Muscle Relaxants, Central; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents; GABA-B Receptor Agonists; GABA Agonists; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action