Efficacy Study of Arbaclofen to Treat Spasticity in Multiple Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01743651
Recruitment Status : Completed
First Posted : December 6, 2012
Last Update Posted : May 28, 2014
Information provided by (Responsible Party):
Osmotica Pharmaceutical US LLC

Brief Summary:

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Drug Information available for: Baclofen
U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: Placebo
Drug: 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
Drug: arbaclofen
10 mg, 15 mg or 20 mg arbaclofen ER tablets administered orally 2 times per day
Drug: Placebo
arbaclofen image matched placebo tablets administered orally 2 times/day or baclofen image matched placebo capsules administered orally 4 times/day
Experimental: Arbaclofen
Drug: baclofen
20 mg, 30 mg or 40 mg baclofen administered orally 4 times per day
Drug: Placebo
arbaclofen image matched placebo tablets administered orally 2 times/day or baclofen image matched placebo capsules administered orally 4 times/day

Primary Outcome Measures :
  1. 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.

  2. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. 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)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients (male or female) 18 to 65 years of age, inclusive, at the time of dosing
  • Have an established diagnosis (per McDonald Criteria) of Multiple Sclerosis (either relapsing remitting or secondary progressive course), that manifests spasticity for at least 6 months
  • Spasticity due to MS as shown by a TNmAS score equal or greater than six (≥6) in the most affected limb.
  • EDSS equal or greater than 3.0
  • If receiving disease-modifying medications, these must have been at a stable dose for at least three (3) months prior to screening, and the subject must be willing to maintain this treatment for the duration of the study
  • Stable regimen for at least thirty (30) days prior to study entry for all medications and non-pharmacological therapies that are intended to alleviate spasticity
  • Absence of infections, peripheral vascular disease, painful contractures, advanced arthritis, or other conditions that hinder evaluation of joint movement
  • Have a creatinine clearance, as calculated by Glomerular Filtration Rate using the Modification of Diet in Renal Disease (MDRD) Study equation, greater than 60mL/min.
  • Use of a medically highly effective of birth control during the study and for ninety (90) days thereafter for women of child-bearing potential (including female subjects and female partners of non-sterile male subjects)
  • Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of participation in the study

Exclusion Criteria:

  • Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity
  • Inability to rate their level of spasticity or distinguish it from other MS symptoms
  • Acute MS exacerbation requiring treatment within twelve (12) weeks of screening
  • Use of intravenous methylprednisolone within the twelve (12) weeks before visit 1
  • Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables
  • Use of botulinum toxin A or B within six (6) months of visit 1
  • History of allergy to baclofen or any inactive component of test or reference formulation
  • Pregnancy, lactation or planned pregnancy during the course of the study and for three (3) months thereafter.
  • History of unstable psychiatric disease, or current signs and symptoms of significant medical disorders such as severe, progressive, or uncontrolled pulmonary, cardiac, gastrointestinal, hepatic, renal, genitourinary, hematological, endocrine, immunologic, or neurological disease
  • History of seizures
  • Current significant cognitive deficit, severe or untreated anxiety, severe or untreated depression
  • Subjects with abnormal micturition that requires indwelling or intermittent catheterization or with lower urinary tract symptoms (LUTS) that result in a score greater than twenty-six (>26) in the Baseline USP© questionnaire
  • Current malignancy or history of malignancy that has not been in remission for more than five (5) years, except effectively treated basal cell skin carcinoma
  • Any other significant disease, disorder or significant laboratory finding which, in the opinion of the investigator, put the subject at risk because of participation, influence the result of the study, or affect the subject's ability to participate
  • Planned elective surgery or other procedures requiring general anesthesia during the study
  • Subject who is inappropriate for placebo medication in the judgment of the Investigator
  • History of substance abuse within the past twelve (12) months
  • Current chronic use of long acting opioids or round the clock use of short acting opioids for the treatment of pain
  • Participation in another research study within thirty (30) days of Screening
  • Patients who are uncooperative or unwilling to sign consent form

Information from the National Library of Medicine

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 identifier (NCT number): NCT01743651

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United States, Alabama
Osmotica Study Site-138
Cullman, Alabama, United States, 35058
United States, California
Osmotica Site-143
Long Beach, California, United States, 92845
United States, Colorado
Osmotica Study Site-123
Aurora, Colorado, United States, 80045
United States, Florida
Osmotica Study Site-110
Bradenton, Florida, United States, 34205
Osmotica Study Site-142
Maitland, Florida, United States, 32751
Osmotica Study Site-119
Ormond Beach, Florida, United States, 32174
Osmotica Study Site-120
Pompano Beach, Florida, United States, 33060
Osmotica Study Site-109
Tampa, Florida, United States, 33606
United States, Illinois
Osmotica Study Site-126
Northbrook, Illinois, United States, 60096
United States, Indiana
Osmotica Study Site-108
Fort Wayne, Indiana, United States, 46805
United States, Kansas
Osmotica Study Site-116
Lenexa, Kansas, United States, 66214
United States, Maryland
Osmotica Study Site-124
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Osmotica Study Site-136
Springfield, Massachusetts, United States, 01104
United States, Michigan
Osmotica Study Site-101
Ann Arbor, Michigan, United States, 48104
United States, New York
Osmotica Study Site-115
Johnson City, New York, United States, 13790
Osmotica Study Site-113
New York, New York, United States, 10016
Osmotica Study Site-141
New York, New York, United States, 10019
Osmotica Study Site-125
New York, New York, United States, 10029
United States, North Carolina
Osmotica Study Site-106
Charlotte, North Carolina, United States, 28204
United States, Ohio
Osmotica Study Site-131
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
Osmotica Study Site-127
Pittsburgh, Pennsylvania, United States, 15212
United States, Texas
Osmotica Study Site-112
San Antonio, Texas, United States, 78229
United States, Utah
Osmotica Study Site-133
Salt Lake City, Utah, United States, 84103
United States, Washington
Osmotica Study Site-129
Seattle, Washington, United States, 98122
Osmotica SIte-144
Tacoma, Washington, United States, 98405
Russian Federation
Osmotica Site-511
Krasnoyarsk, Russian Federation
Osmotica Study Site-508
Krasnoyarsk, Russian Federation
Osmotica Study Site-510
Krasnoyarsk, Russian Federation
Osmotica Study Site-501
Moscow, Russian Federation
Osmotica Study Site-502
Moscow, Russian Federation
Osmotica Study Site-509
Pyatigorsk, Stavropol Region, Russian Federation
Osmotica Study Site-506
Sestroretsk, St. Petersburg, Russian Federation
Osmotica Study Site-507
St Petersburg, Russian Federation
Osmotica Study Site-503
St. Petersburg, Russian Federation
Osmotica Study Site-505
St. Petersburg, Russian Federation
Osmotica Study Site-510
Tonnelniy, Kochubeev District, Stavropol Region, Russian Federation
Osmotica Study Site 614
Chernigov, Ukraine, 14001
Osmotica Study Site-602
Dnipropetrovsk, Ukraine, 49005
Osmotica Study Site-603
Dnipropetrovsk, Ukraine, 49022
Osmotica Study Site-609
Dnipropetrovsk, Ukraine, 53012
Osmotica Study Site-611
Donetsk, Ukraine, 83003
Osmotica Study Site-613
Ivano-Frankivsk, Ukraine, 76008
Osmotica Site-605
Kharkov, Ukraine, 61068
Osmotica Study Site-610
Kharkov, Ukraine, 61103
Osmotica Study Site-604
Kharkov, Ukraine
Osmotica Study Site-606
Lviv, Ukraine
Osmotica Study Site-608
Odessa, Ukraine
Osmotica Study Site-615
Uzhgorod, Ukraine, 88018
Sponsors and Collaborators
Osmotica Pharmaceutical US LLC
Study Chair: Praveen Tyle, PhD Osmotica Pharmaceutical

Responsible Party: Osmotica Pharmaceutical US LLC Identifier: NCT01743651     History of Changes
Other Study ID Numbers: OS440-3002
First Posted: December 6, 2012    Key Record Dates
Last Update Posted: May 28, 2014
Last Verified: May 2014

Keywords provided by Osmotica Pharmaceutical US LLC:
multiple sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Muscle Spasticity
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Signs and Symptoms