Back to resultsA Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS (OS440-3004)
Primary Purpose
Multiple Sclerosis, Spasticity, Muscle
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Arbaclofen
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria Includes:
- Subjects 18 to 65 years of age, inclusive.
- An established diagnosis of MS that manifests a documented history of spasticity.
- If receiving disease-modifying medications (eg, interferons approved for MS, glatiramer acetate, natalizumab, fingolimod, or mitoxantrone), there must be no change in dose for at least 3 months prior to Visit 1 (Screening), and the subject must be willing to maintain this treatment dose for the duration of the study. If receiving AMPYRA® (dalfampridine, fampridine, 4-amino puridine), subject must be at a stable dose for at least 3 months prior to Visit 1.
- Stable regimen for at least 3 months prior to Visit 2 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.
- Use of a medically highly effective form of birth control (see Section 7.8) during the study and for 3 months thereafter for women of child-bearing potential (including female subjects and female partners of non-sterile male subjects).
- Willing to sign the informed consent form (ICF).
Exclusion Criteria Includes:
- Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity.
- Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables.
- Pregnancy, lactation, or planned pregnancy during the course of the study and for 3 months after the final study visit.
- Subject has clinically significant abnormal laboratory values, in the opinion of the investigator, at Visit 1 or Visit 2.
- Current malignancy or history of malignancy that has not been in remission for more than 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, puts the subject at risk because of participation, influences the result of the study, or affects the subject's ability to participate.
Sites / Locations
- Grodno Regional Clinical Hospital
- Minsk City Clinical Hospital #5
- Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
- Republican Research and Development Center for Neurology and Neurosurgery
- Vitebsk Regional Diagnostic Center
- University Clinical Centre of the Republic of Srpska, Clinic of Neurology
- University Clinical Hospital Mostar, Clinic of Neurology
- Multiprofile Hospital for Active Treatment - Pleven within the structure of Military Medical Academy, Sofia
- University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Clinic of Neurological Diseases
- Medical Center "Rusemed" EOOD
- Multiprofile Hospital for Active Treatment "ACIBADEM City Clinic Tokuda Hospital", Sofia, Neurology and Sleep Medicine Clinic
- Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia
- University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Neurology Diseases
- Clinical Hospital Center Osijek, Clinic of Neurology
- Clinical Hospital Center Rijeka, Department of Neurology
- General Hospital Varazdin, Department of Neurology
- Clinical Hospital Dubrava, Department of Neurology
- Institute for Emergency Medicine
- National Institute of Neurology and Neurosurgery
- Dendryt Medical Center
- Neuro-Medic
- Medical Practice Professor K. Rejdak
- MED-Polonia, Sp. z o.o. (LLC)
- "MEDYK" Stanislaw Mazur Sp. z o.o. (LLC) Medical Centre
- NeuroProtect Medical Center
- Neurology Center Krzysztof Selmaj
- Clinical Center of Serbia
- Clinical Hospital Center Zemun, Department of Neurology
- Clinical Hospital Center Zvezdara
- Clinical Center Kragujevac
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
AERT 40 mg
AERT 80 mg
Placebo
Arm Description
40 mg Arbaclofen Extended-Release Tablets
80 mg Arbaclofen Extended-Release Tablets
Placebo
Outcomes
Primary Outcome Measures
Change From Baseline in Total Numeric-transformed Modified Ashworth Scale Score of the Most Affected Limb (TNmAS-MAL)
Total Numeric-Transformed Modified Ashworth Scale (TNmAS) is a 6-point scale to measure abnormality in tone or the resistance to passive movements. Higher score is worse outcome.
For each joint, the minimum score is 0; maximum score is 5. The values for each of the 3 main joints are summed for the limb score. The limb with the highest score is the most affected limb (MAL). The highest possible score for a limb is 15. Limb range: 0 to 15.
To arrive at total limbs (TL) score the values for all 4 limbs are summed; maximum total limb score is 60. TL range: 0 to 60.
Clinical Global Impression of Change (CGIC)
The Clinical Global Impression of Change (CGIC) was developed to provide a brief, stand-alone assessment of the clinician's view of the subject's global functioning prior to and after initiating a study medication. The scale ranges from -3 to +3 judging whether the change is significantly worse (-3) to significantly improved (+3). Higher score is better outcome. The CGIC scale will be used to measure the overall change in the subject's condition since starting the study. There is no baseline value because the score is a measure of how the patient changed from baseline (treatment initiation).
Secondary Outcome Measures
Full Information
NCT ID
NCT03290131
First Posted
September 19, 2017
Last Updated
July 12, 2022
Sponsor
RVL Pharmaceuticals, Inc.
Collaborators
Osmotica Pharmaceutical US LLC
1. Study Identification
Unique Protocol Identification Number
NCT03290131
Brief Title
A Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS
Acronym
OS440-3004
Official Title
A Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Investigate the Safety and Efficacy of Arbaclofen Extended-Release Tablets for the Treatment of Spasticity in Patients With Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
January 28, 2018 (Actual)
Primary Completion Date
December 3, 2018 (Actual)
Study Completion Date
January 2, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RVL Pharmaceuticals, Inc.
Collaborators
Osmotica Pharmaceutical US LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Multiple Sclerosis (MS) is an acquired inflammatory demyelinating disease of the central nervous system (CNS) that is regarded as the foremost cause of non-traumatic neurologic disability in adults in North America. Spasticity is a common complication in MS and occurs in up to 84% of patients. The main sign of spasticity is resistance to passive limb movement characterized by increased resistance to stretching, clonus, and exaggerated deep reflexes. Osmotica Pharmaceutical is currently developing arbaclofen extended-release tablets (AERT) for the treatment of spasticity in patients with MS.
Detailed Description
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of oral AERT in MS patients with spasticity. Two doses of AERT, 40 mg and 80 mg, will be compared with placebo. The treatment groups will be randomized in a 1:1:1 ratio. Eligible patients will undergo a washout period for withdrawal of all medications used for anti-spasticity and/or muscle relaxation prior to randomization. A baseline clinical evaluation will be performed (Visit 2) to confirm eligibility for study randomization, and subjects will be randomly assigned to 1 of 3 treatment arms. Subjects will remain on maintenance treatment for approximately 3 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Spasticity, Muscle
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
536 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AERT 40 mg
Arm Type
Active Comparator
Arm Description
40 mg Arbaclofen Extended-Release Tablets
Arm Title
AERT 80 mg
Arm Type
Active Comparator
Arm Description
80 mg Arbaclofen Extended-Release Tablets
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Arbaclofen
Other Intervention Name(s)
AERT
Intervention Description
Arbaclofen Extended Release Tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo comparator
Primary Outcome Measure Information:
Title
Change From Baseline in Total Numeric-transformed Modified Ashworth Scale Score of the Most Affected Limb (TNmAS-MAL)
Description
Total Numeric-Transformed Modified Ashworth Scale (TNmAS) is a 6-point scale to measure abnormality in tone or the resistance to passive movements. Higher score is worse outcome.
For each joint, the minimum score is 0; maximum score is 5. The values for each of the 3 main joints are summed for the limb score. The limb with the highest score is the most affected limb (MAL). The highest possible score for a limb is 15. Limb range: 0 to 15.
To arrive at total limbs (TL) score the values for all 4 limbs are summed; maximum total limb score is 60. TL range: 0 to 60.
Time Frame
84 days
Title
Clinical Global Impression of Change (CGIC)
Description
The Clinical Global Impression of Change (CGIC) was developed to provide a brief, stand-alone assessment of the clinician's view of the subject's global functioning prior to and after initiating a study medication. The scale ranges from -3 to +3 judging whether the change is significantly worse (-3) to significantly improved (+3). Higher score is better outcome. The CGIC scale will be used to measure the overall change in the subject's condition since starting the study. There is no baseline value because the score is a measure of how the patient changed from baseline (treatment initiation).
Time Frame
84 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Includes:
Subjects 18 to 65 years of age, inclusive.
An established diagnosis of MS that manifests a documented history of spasticity.
If receiving disease-modifying medications (eg, interferons approved for MS, glatiramer acetate, natalizumab, fingolimod, or mitoxantrone), there must be no change in dose for at least 3 months prior to Visit 1 (Screening), and the subject must be willing to maintain this treatment dose for the duration of the study. If receiving AMPYRA® (dalfampridine, fampridine, 4-amino puridine), subject must be at a stable dose for at least 3 months prior to Visit 1.
Stable regimen for at least 3 months prior to Visit 2 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.
Use of a medically highly effective form of birth control (see Section 7.8) during the study and for 3 months thereafter for women of child-bearing potential (including female subjects and female partners of non-sterile male subjects).
Willing to sign the informed consent form (ICF).
Exclusion Criteria Includes:
Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity.
Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables.
Pregnancy, lactation, or planned pregnancy during the course of the study and for 3 months after the final study visit.
Subject has clinically significant abnormal laboratory values, in the opinion of the investigator, at Visit 1 or Visit 2.
Current malignancy or history of malignancy that has not been in remission for more than 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, puts the subject at risk because of participation, influences the result of the study, or affects the subject's ability to participate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Jacobs, MD
Organizational Affiliation
Vice President
Official's Role
Study Director
Facility Information:
Facility Name
Grodno Regional Clinical Hospital
City
Grodno
Country
Belarus
Facility Name
Minsk City Clinical Hospital #5
City
Minsk
Country
Belarus
Facility Name
Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
City
Minsk
Country
Belarus
Facility Name
Republican Research and Development Center for Neurology and Neurosurgery
City
Minsk
Country
Belarus
Facility Name
Vitebsk Regional Diagnostic Center
City
Vitebsk
Country
Belarus
Facility Name
University Clinical Centre of the Republic of Srpska, Clinic of Neurology
City
Banja Luka
Country
Bosnia and Herzegovina
Facility Name
University Clinical Hospital Mostar, Clinic of Neurology
City
Mostar
Country
Bosnia and Herzegovina
Facility Name
Multiprofile Hospital for Active Treatment - Pleven within the structure of Military Medical Academy, Sofia
City
Pleven
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Clinic of Neurological Diseases
City
Pleven
Country
Bulgaria
Facility Name
Medical Center "Rusemed" EOOD
City
Ruse
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment "ACIBADEM City Clinic Tokuda Hospital", Sofia, Neurology and Sleep Medicine Clinic
City
Sofia
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia
City
Sofia
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Neurology Diseases
City
Sofia
Country
Bulgaria
Facility Name
Clinical Hospital Center Osijek, Clinic of Neurology
City
Osijek
Country
Croatia
Facility Name
Clinical Hospital Center Rijeka, Department of Neurology
City
Rijeka
Country
Croatia
Facility Name
General Hospital Varazdin, Department of Neurology
City
Varaždin
Country
Croatia
Facility Name
Clinical Hospital Dubrava, Department of Neurology
City
Zagreb
Country
Croatia
Facility Name
Institute for Emergency Medicine
City
Chisinau
Country
Moldova, Republic of
Facility Name
National Institute of Neurology and Neurosurgery
City
Chisinau
Country
Moldova, Republic of
Facility Name
Dendryt Medical Center
City
Katowice
Country
Poland
Facility Name
Neuro-Medic
City
Katowice
Country
Poland
Facility Name
Medical Practice Professor K. Rejdak
City
Lublin
Country
Poland
Facility Name
MED-Polonia, Sp. z o.o. (LLC)
City
Poznań
Country
Poland
Facility Name
"MEDYK" Stanislaw Mazur Sp. z o.o. (LLC) Medical Centre
City
Rzeszów
Country
Poland
Facility Name
NeuroProtect Medical Center
City
Warsaw
Country
Poland
Facility Name
Neurology Center Krzysztof Selmaj
City
Łódź
Country
Poland
Facility Name
Clinical Center of Serbia
City
Belgrade
Country
Serbia
Facility Name
Clinical Hospital Center Zemun, Department of Neurology
City
Belgrade
Country
Serbia
Facility Name
Clinical Hospital Center Zvezdara
City
Belgrade
Country
Serbia
Facility Name
Clinical Center Kragujevac
City
Kragujevac
Country
Serbia
12. IPD Sharing Statement
Learn more about this trial
A Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS
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