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

XenoPort

Status and phase: Completed; Phase 3

Conditions: Multiple Sclerosis

Treatments: Drug: Arbaclofen placarbil 45 mg BID; Drug: Placebo; Drug: Arbaclofen placarbil 15 mg BID; Drug: Arbaclofen placarbil 30 mg BID

Study type: Interventional

Funder types: Industry

Identifiers

NCT01359566

XP-B-089

Details and patient eligibility

About

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).

Enrollment: 228 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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228 participants in 4 patient groups, including a placebo group

Arbaclofen placarbil 15 mg BID

Active Comparator group

Description:

Arbaclofen placarbil (XP19986 SR4) 15 mg every morning and every evening

Treatment:

Drug: Arbaclofen placarbil 15 mg BID

Arbaclofen placarbil 30 mg BID

Active Comparator group

Description:

Arbaclofen placarbil (XP19986 SR4) 30 mg every morning and every evening

Treatment:

Drug: Arbaclofen placarbil 30 mg BID

Arbaclofen placarbil 45 mg BID

Active Comparator group

Description:

Arbaclofen placarbil (XP19986 SR4) 45 mg every morning and every evening

Treatment:

Drug: Arbaclofen placarbil 45 mg BID

Placebo

Placebo Comparator group

Description:

Placebo every morning and every evening

Treatment:

Drug: Placebo