Efficacy Study of Arbaclofen to Treat Spasticity in Multiple Sclerosis

NCT01743651 | Completed Phase 3 DMC

• 1 other identifier: OS440-3002
• Study Type: interventional
• Target: 353
• Locations: 3 countries
• Sites: 48

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.

Conditions

Spasticity; Multiple Sclerosis

Keywords

spasticity; multiple sclerosis; arbaclofen

Outcome Measures

Primary Outcomes (2)

• Efficacy as determined by Total Numeric Transformed Modified Ashworth scale (TNmAS) in the most affected limb.

  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.

  Change in baseline from Visit 1 through Visit 9 (120 days) or end of treatment

• Clinical Global Impression of Change (CGIC) through end of treatment

  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.

  Visit 9 (120 days) or end of study

Secondary Outcomes (9)

• Changes in the Multiple Sclerosis Spasticity Scale (MSSS-88)

  Baseline through Visit 9 (120 days)

• Changes in the TNmAS for the most affected limb

  From baseline to visits 4 (22 days), 5 (36 days), 6 (50 days), 7 (71 days), and 9 (120 days)

• Changes in the TNmAS for the sum of all limbs

  Baseline to visits 4 (22 days), 5 (36 days), 6 (50 days), 7 (71 days), and 9 (120 days)

• Changes in Expanded Disability Status Score (EDSS)

  Baseline to Visit 9 (120 Days)

• Changes in the Lower Extremity Manual Muscle Testing (LEMMT) Scale

  Baseline to Visit 4 (22 days), Visit 5 (36 days) Visit 6 (50 days) Visit 7 (71 days) and Visit 9 (120 days)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Baclofen

ACTIVE COMPARATOR

80 mg/day of Baclofen Tablets, USP

Drug: baclofen

Arbaclofen

EXPERIMENTAL

40 mg/day of Arbaclofen Tablets

Drug: arbaclofen

Interventions

arbaclofen DRUG

40 mg/day as 20 mg arbaclofen ER administered orally 2 times per day

Also known as: OS440, AERT

Arbaclofen

baclofen DRUG

80 mg/day as 20 mg baclofen administered orally 4 times per day

Baclofen

Placebo DRUG

arbaclofen image matched placebo tablets administered orally 2 times/day or baclofen image matched placebo capsules administered orally 4 times/day

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• RVL Pharmaceuticals, Inc.: lead
• Osmotica Pharmaceutical US LLC: collaborator

Study Sites (48)

Osmotica Study Site-138

Cullman, Alabama, 35058, United States

Location

Osmotica Site-143

Long Beach, California, 92845, United States

Location

Osmotica Study Site-123

Aurora, Colorado, 80045, United States

Location

Osmotica Study Site-110

Bradenton, Florida, 34205, United States

Location

Osmotica Study Site-142

Maitland, Florida, 32751, United States

Location

Osmotica Study Site-119

Ormond Beach, Florida, 32174, United States

Location

Osmotica Study Site-120

Pompano Beach, Florida, 33060, United States

Location

Osmotica Study Site-109

Tampa, Florida, 33606, United States

Location

Osmotica Study Site-126

Northbrook, Illinois, 60096, United States

Location

Osmotica Study Site-108

Fort Wayne, Indiana, 46805, United States

Location

Osmotica Study Site-116

Lenexa, Kansas, 66214, United States

Location

Osmotica Study Site-124

Baltimore, Maryland, 21201, United States

Location

Osmotica Study Site-136

Springfield, Massachusetts, 01104, United States

Location

Osmotica Study Site-101

Ann Arbor, Michigan, 48104, United States

Location

Osmotica Study Site-115

Johnson City, New York, 13790, United States

Location

Osmotica Study Site-113

New York, New York, 10016, United States

Location

Osmotica Study Site-141

New York, New York, 10019, United States

Location

Osmotica Study Site-125

New York, New York, 10029, United States

Location

Osmotica Study Site-106

Charlotte, North Carolina, 28204, United States

Location

Osmotica Study Site-131

Cincinnati, Ohio, 45219, United States

Location

Osmotica Study Site-127

Pittsburgh, Pennsylvania, 15212, United States

Location

Osmotica Study Site-112

San Antonio, Texas, 78229, United States

Location

Osmotica Study Site-133

Salt Lake City, Utah, 84103, United States

Location

Osmotica Study Site-129

Seattle, Washington, 98122, United States

Location

Osmotica SIte-144

Tacoma, Washington, 98405, United States

Location

Osmotica Study Site-509

Pyatigorsk, Stavropol Kray, Russia

Location

Osmotica Study Site-510

Tonnel’nyy, Stavropol Kray, Russia

Location

Osmotica Site-511

Krasnoyarsk, Russia

Location

Osmotica Study Site-508

Krasnoyarsk, Russia

Location

Osmotica Study Site-510

Krasnoyarsk, Russia

Location

Osmotica Study Site-501

Moscow, Russia

Location

Osmotica Study Site-502

Moscow, Russia

Location

Osmotica Study Site-503

Saint Petersburg, Russia

Location

Osmotica Study Site-505

Saint Petersburg, Russia

Location

Osmotica Study Site-507

Saint Petersburg, Russia

Location

Osmotica Study Site-506

Sestroretsk, Russia

Location

Osmotica Study Site 614

Chernihiv, 14001, Ukraine

Location

Osmotica Study Site-602

Dnipropetrovsk, 49005, Ukraine

Location

Osmotica Study Site-603

Dnipropetrovsk, 49022, Ukraine

Location

Osmotica Study Site-609

Dnipropetrovsk, 53012, Ukraine

Location

Osmotica Study Site-611

Donetsk, 83003, Ukraine

Location

Osmotica Study Site-613

Ivano-Frankivsk, 76008, Ukraine

Location

Osmotica Site-605

Kharkiv, 61068, Ukraine

Location

Osmotica Study Site-610

Kharkiv, 61103, Ukraine

Location

Osmotica Study Site-604

Kharkiv, Ukraine

Location

Osmotica Study Site-606

Lviv, Ukraine

Location

Osmotica Study Site-608

Odesa, Ukraine

Location

Osmotica Study Site-615

Uzhhorod, 88018, Ukraine

Location

MeSH Terms

Conditions

Muscle Spasticity; Multiple Sclerosis

Interventions

arbaclofen placarbil; Baclofen

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Praveen Tyle, PhD

  Osmotica Pharmaceutical

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: December 6, 2012
• Study Start: November 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 25, 2022

Record last verified: 2014-05

Locations

RU (11); US (25); UA (12)