Efficacy Study of Arbaclofen to Treat Spasticity in Multiple Sclerosis
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|ClinicalTrials.gov Identifier: NCT01743651|
Recruitment Status : Completed
First Posted : December 6, 2012
Last Update Posted : May 11, 2021
This is a multicenter, randomized (1:1:1), double-blind, active and placebo controlled, parallel group study to evaluate safety, tolerability and efficacy of oral arbaclofen in MS patients with spasticity.
Eligible subjects will be removed from anti-spasticity mediations for at least one week and then begin study drug treatment with daily doses increasing up to the target dose which will then be maintained for at least 12 weeks. A down-titration will then occur over two weeks with the final study visit occuring at 19 weeks from start of achieving the target dose or 22 weeks from the Study Visit 1.
|Condition or disease||Intervention/treatment||Phase|
|Spasticity Multiple Sclerosis||Drug: arbaclofen Drug: baclofen Drug: Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||353 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-Blind, Parallel Group Study to Compare the Safety and Efficacy Arbaclofen ER Tablets to Placebo and Baclofen Tablets, USP for the Treatment of Spasticity in Patients With Multiple Sclerosis|
|Study Start Date :||November 2012|
|Actual Primary Completion Date :||April 2014|
|Actual Study Completion Date :||April 2014|
Placebo Comparator: Placebo
arbaclofen image matched placebo tablets administered orally 2 times/day or baclofen image matched placebo capsules administered orally 4 times/day
Active Comparator: Baclofen
20 mg, 30 mg or 40 mg baclofen administered orally 4 times per day
10 mg, 15 mg or 20 mg arbaclofen ER tablets administered orally 2 times per day
- Efficacy as determined by Total Numeric Transformed Modified Ashworth scale (TNmAS) in the most affected limb. [ Time Frame: Change in baseline from Visit 1 through Visit 9 (120 days) or end of treatment ]Change from baseline through end of treatment in the pre-dose, morning TNmAS of the most affected limb. The most affected limb is determined at baseline using the sum of scores for three major motor groups. High scores indicate more severe spasticity.
- Clinical Global Impression of Change (CGIC) through end of treatment [ Time Frame: Visit 9 (120 days) or end of study ]The CGIC is a global rating scale that captures the investigator's assessment of the subject's change in overall functional performance since starting the study. Scores range from -3 (significant worsening) to +3 (significant improvement.
- Changes in the Multiple Sclerosis Spasticity Scale (MSSS-88) [ Time Frame: Baseline through Visit 9 (120 days) ]This MSSS-88 is a self-administered questionnaire for the subject to assess overall functional performance and sense of impairment with respect to the level of spasticity.
- Changes in the TNmAS for the most affected limb [ Time Frame: From baseline to visits 4 (22 days), 5 (36 days), 6 (50 days), 7 (71 days), and 9 (120 days) ]The modified Ashworth Scale is a six (6)-point rating scale that measures abnormality in tone or the resistance to passive movements. Measurements are made in three muscle groups of each limb. The most affect limb is determined at baseline, based on the sum of scores from each limb. Higher scores indicate more severe spasticity.
- Changes in the TNmAS for the sum of all limbs [ Time Frame: Baseline to visits 4 (22 days), 5 (36 days), 6 (50 days), 7 (71 days), and 9 (120 days) ]The sums of scores from all limbs are compared to the baseline sum. Higher scores indicate more severe spasticity.
- Changes in Expanded Disability Status Score (EDSS) [ Time Frame: Baseline to Visit 9 (120 Days) ]The EDSS is based on an examination by a neurologist with a scale that ranges from zero (0) to ten (10) in half point (0.5) unit increments. Higher scores represent higher levels of disability.
- Changes in the Lower Extremity Manual Muscle Testing (LEMMT) Scale [ Time Frame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days) ]The LEMMT Scale is an evaluation of the function and strength of individual muscles and muscle groups based on effective performance of limb movement in relation to the forces of gravity and manual resistance. Maximum muscular strength is the maximum amount of tension or force that a muscle or muscle group can voluntarily exert in one maximal effort. Scores for each muscle or muscle group range from 0 (no detectable activity) to 5 (normal activity).
- Changes in Epworth Sleepiness Scale (ESS) [ Time Frame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days) ]The ESS is used to determine the level of daytime sleepiness. The questionnaire asks the subject to rate his or her probability of falling asleep on a scale of increasing probability from 0 to 3 in eight different situations.
- Changes in the subject-recorded mean daily Drowsiness Numerical Rating Scale (DNRS)score for the day prior to each visit [ Time Frame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days) ]Drowsiness will be reported by the subject using a numerical rating scale with a range of zero (0; no drowsiness) to ten (10; worst possible drowsiness). Scores will be recorded every 3 hours during the day before each designated visit.
- Changes in the Urinary Symptom Profile (USP) Scale [ Time Frame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days) ]The USP is a Health-Related Quality of Life questionnaire composed of 13 items assessing urinary symptoms in adults with stress, urge, overactive bladder, or urinary obstructive symptoms.
- Clinical Global Impression of Change (CGIC) [ Time Frame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) ]The CGIC scores will be recorded at the designated intervals prior to Visit 9 (end of study)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01743651
|Study Chair:||Praveen Tyle, PhD||Osmotica Pharmaceutical|