Clinical trial NCT01743651: Efficacy Study of Arbaclofen to Treat Spasticity in Multiple Sclerosis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spasticity
Multiple Sclerosis
Keywords: spasticity
multiple sclerosis
arbaclofen
Lead sponsor: RVL Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Osmotica Pharmaceutical US LLC
First posted: 2012-12-06
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 medications 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.

Detailed description: 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 medications 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 occurring at 19 weeks from start of achieving the target dose or 22 weeks from the Study Visit 1.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy as determined by Total Numeric Transformed Modified Ashworth scale (TNmAS) in the most affected limb.
timeFrame: Change in baseline from Visit 1 through Visit 9 (120 days) or end of treatment
measure: Clinical Global Impression of Change (CGIC) through end of treatment
timeFrame: Visit 9 (120 days) or end of study
Secondary outcomes:
measure: Changes in the Multiple Sclerosis Spasticity Scale (MSSS-88)
timeFrame: Baseline through Visit 9 (120 days)
measure: Changes in the TNmAS for the most affected limb
timeFrame: From baseline to visits 4 (22 days), 5 (36 days), 6 (50 days), 7 (71 days), and 9 (120 days)
measure: Changes in the TNmAS for the sum of all limbs
timeFrame: Baseline to visits 4 (22 days), 5 (36 days), 6 (50 days), 7 (71 days), and 9 (120 days)
measure: Changes in Expanded Disability Status Score (EDSS)
timeFrame: Baseline to Visit 9 (120 Days)
measure: Changes in the Lower Extremity Manual Muscle Testing (LEMMT) Scale
timeFrame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days)
measure: Changes in Epworth Sleepiness Scale (ESS)
timeFrame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days)
measure: Changes in the subject-recorded mean daily Drowsiness Numerical Rating Scale (DNRS)score for the day prior to each visit
timeFrame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days)
measure: Changes in the Urinary Symptom Profile (USP) Scale
timeFrame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days)
measure: Clinical Global Impression of Change (CGIC)
timeFrame: Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days)
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Osmotica Study Site-138
state: Alabama
city: Long Beach
country: United States
facility: Osmotica Site-143
state: California
city: Aurora
country: United States
facility: Osmotica Study Site-123
state: Colorado
city: Bradenton
country: United States
facility: Osmotica Study Site-110
state: Florida
city: Maitland
country: United States
facility: Osmotica Study Site-142
state: Florida
city: Ormond Beach
country: United States
facility: Osmotica Study Site-119
state: Florida
city: Pompano Beach
country: United States
facility: Osmotica Study Site-120
state: Florida
city: Tampa
country: United States
facility: Osmotica Study Site-109
state: Florida
city: Northbrook
country: United States
facility: Osmotica Study Site-126
state: Illinois
city: Fort Wayne
country: United States
facility: Osmotica Study Site-108
state: Indiana
city: Lenexa
country: United States
facility: Osmotica Study Site-116
state: Kansas
city: Baltimore
country: United States
facility: Osmotica Study Site-124
state: Maryland
city: Springfield
country: United States
facility: Osmotica Study Site-136
state: Massachusetts
city: Ann Arbor
country: United States
facility: Osmotica Study Site-101
state: Michigan
city: Johnson City
country: United States
facility: Osmotica Study Site-115
state: New York
city: New York
country: United States
facility: Osmotica Study Site-113
state: New York
city: New York
country: United States
facility: Osmotica Study Site-141
state: New York
city: New York
country: United States
facility: Osmotica Study Site-125
state: New York
city: Charlotte
country: United States
facility: Osmotica Study Site-106
state: North Carolina
city: Cincinnati
country: United States
facility: Osmotica Study Site-131
state: Ohio
city: Pittsburgh
country: United States
facility: Osmotica Study Site-127
state: Pennsylvania
city: San Antonio
country: United States
facility: Osmotica Study Site-112
state: Texas
city: Salt Lake City
country: United States
facility: Osmotica Study Site-133
state: Utah
city: Seattle
country: United States
facility: Osmotica Study Site-129
state: Washington
city: Tacoma
country: United States
facility: Osmotica SIte-144
state: Washington
city: Pyatigorsk
country: Russian Federation
facility: Osmotica Study Site-509
state: Stavropol Krai
city: Tonnel'nyy
country: Russian Federation
facility: Osmotica Study Site-510
state: Stavropol Krai
city: Krasnoyarsk
country: Russian Federation
facility: Osmotica Site-511
city: Krasnoyarsk
country: Russian Federation
facility: Osmotica Study Site-508
city: Krasnoyarsk
country: Russian Federation
facility: Osmotica Study Site-510
city: Moscow
country: Russian Federation
facility: Osmotica Study Site-501
city: Moscow
country: Russian Federation
facility: Osmotica Study Site-502
city: Sestroretsk
country: Russian Federation
facility: Osmotica Study Site-506
city: St Petersburg
country: Russian Federation
facility: Osmotica Study Site-507
city: St. Petersburg
country: Russian Federation
facility: Osmotica Study Site-503
city: St. Petersburg
country: Russian Federation
facility: Osmotica Study Site-505
city: Chernigov
country: Ukraine
facility: Osmotica Study Site 614
city: Dnipropetrovsk
country: Ukraine
facility: Osmotica Study Site-602
city: Dnipropetrovsk
country: Ukraine
facility: Osmotica Study Site-603
city: Dnipropetrovsk
country: Ukraine
facility: Osmotica Study Site-609
city: Donetsk
country: Ukraine
facility: Osmotica Study Site-611
city: Ivano-Frankivsk
country: Ukraine
facility: Osmotica Study Site-613
city: Kharkov
country: Ukraine
facility: Osmotica Site-605
city: Kharkov
country: Ukraine
facility: Osmotica Study Site-610
city: Kharkov
country: Ukraine
facility: Osmotica Study Site-604
city: Lviv
country: Ukraine
facility: Osmotica Study Site-606
city: Odessa
country: Ukraine
facility: Osmotica Study Site-608
city: Uzhgorod
country: Ukraine
facility: Osmotica Study Site-615
Study officials:
affiliation: Osmotica Pharmaceutical
name: Praveen Tyle, PhD
role: STUDY_CHAIR
References: