Clinical trial NCT01359566: Efficacy and Safety of Arbaclofen Placarbil in Subjects With Spasticity Due to Multiple Sclerosis
Official title: A Randomized, Double Blind, Placebo-Controlled Efficacy and Safety Study of Arbaclofen Placarbil in Subjects With Spasticity Due to Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: XenoPort, Inc.
Sponsor class: INDUSTRY
First posted: 2011-05-24
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Change from Baseline in Maximum Ashworth Scale score (6 hour post-dose time point)
timeFrame: 10-weeks
measure: Patient Global Impression of Change (PGIC) score
timeFrame: 10-weeks
Secondary outcomes:
measure: Change in the overall Modified PRISM score
timeFrame: Weeks 4, 6, 10
measure: Change in weekly average severity of pain score associated with muscle spasm.
timeFrame: Week 10
measure: Change in weekly average VAS score of sleep quality
timeFrame: Week 10
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: XenoPort Clinical Site
state: Arizona
city: Tucson
country: United States
facility: XenoPort Clinical Site
state: Arizona
city: Berkeley
country: United States
facility: XenoPort Clinical Site
state: California
city: San Diego
country: United States
facility: XenoPort Clinical Site
state: California
city: Denver
country: United States
facility: XenoPort Clinical Site
state: Colorado
city: Port Charlotte
country: United States
facility: XenoPort Clinical Site
state: Florida
city: Saint Petersburg
country: United States
facility: XenoPort Clinical Site
state: Florida
city: Sarasota
country: United States
facility: XenoPort Clinical Site
state: Florida
city: Tampa
country: United States
facility: XenoPort Clinical Site
state: Florida
city: Lake Barrington
country: United States
facility: XenoPort Clinical Site
state: Illinois
city: Indianapolis
country: United States
facility: XenoPort Clinical Site
state: Indiana
city: Lenexa
country: United States
facility: XenoPort Clinical Site
state: Kansas
city: Lexington
country: United States
facility: XenoPort Clinical Site
state: Kentucky
city: Bingham Farms
country: United States
facility: XenoPort Clinical Site
state: Michigan
city: Detroit
country: United States
facility: XenoPort Clinical Site
state: Michigan
city: Toms River
country: United States
facility: XenoPort Clinical Site
state: New Jersey
city: Albuquerque
country: United States
facility: XenoPort Clinical Site
state: New Mexico
city: Albany
country: United States
facility: XenoPort Clinical Site
state: New York
city: Patchogue
country: United States
facility: XenoPort Clinical Site
state: New York
city: Plainview
country: United States
facility: XenoPort Clinical Site
state: New York
city: Asheville
country: United States
facility: XenoPort Clinical Site
state: North Carolina
city: Akron
country: United States
facility: XenoPort Clinical Site
state: Ohio
city: Franklin
country: United States
facility: XenoPort Clinical Site
state: Tennessee
city: Nashville
country: United States
facility: XenoPort Clinical Site
state: Tennessee
city: San Antonio
country: United States
facility: XenoPort Clinical Site
state: Texas
city: Vienna
country: United States
facility: XenoPort Clinical Site
state: Virginia
city: Seattle
country: United States
facility: XenoPort Clinical Site
state: Washington
city: Tacoma
country: United States
facility: XenoPort Clinical Site
state: Washington
Study officials:
affiliation: Indivior Inc.
name: Study Director
role: STUDY_DIRECTOR
References: