Clinical trial NCT03290131: A Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Spasticity, Muscle
Lead sponsor: RVL Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Osmotica Pharmaceutical US LLC
First posted: 2017-09-21
Enrollment: 536
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: 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.

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.

Primary outcomes:
measure: Change From Baseline in Total Numeric-transformed Modified Ashworth Scale Score of the Most Affected Limb (TNmAS-MAL)
timeFrame: 84 days
measure: Clinical Global Impression of Change (CGIC)
timeFrame: 84 days
Secondary outcomes:
Other outcomes:
Locations:
city: Grodno
country: Belarus
facility: Grodno Regional Clinical Hospital
city: Minsk
country: Belarus
facility: Minsk City Clinical Hospital #5
city: Minsk
country: Belarus
facility: Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology
city: Minsk
country: Belarus
facility: Republican Research and Development Center for Neurology and Neurosurgery
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Diagnostic Center
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska, Clinic of Neurology
city: Mostar
country: Bosnia and Herzegovina
facility: University Clinical Hospital Mostar, Clinic of Neurology
city: Pleven
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Pleven within the structure of Military Medical Academy, Sofia
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Clinic of Neurological Diseases
city: Ruse
country: Bulgaria
facility: Medical Center "Rusemed" EOOD
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "ACIBADEM City Clinic Tokuda Hospital", Sofia, Neurology and Sleep Medicine Clinic
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Neurology Diseases
city: Osijek
country: Croatia
facility: Clinical Hospital Center Osijek, Clinic of Neurology
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka, Department of Neurology
city: Varaždin
country: Croatia
facility: General Hospital Varazdin, Department of Neurology
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava, Department of Neurology
city: Chisinau
country: Moldova, Republic of
facility: Institute for Emergency Medicine
city: Chisinau
country: Moldova, Republic of
facility: National Institute of Neurology and Neurosurgery
city: Katowice
country: Poland
facility: Dendryt Medical Center
city: Katowice
country: Poland
facility: Neuro-Medic
city: Lublin
country: Poland
facility: Medical Practice Professor K. Rejdak
city: Poznań
country: Poland
facility: MED-Polonia, Sp. z o.o. (LLC)
city: Rzeszów
country: Poland
facility: "MEDYK" Stanislaw Mazur Sp. z o.o. (LLC) Medical Centre
city: Warsaw
country: Poland
facility: NeuroProtect Medical Center
city: Łódź
country: Poland
facility: Neurology Center Krzysztof Selmaj
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zemun, Department of Neurology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
Study officials:
affiliation: Vice President
name: David Jacobs, MD
role: STUDY_DIRECTOR
References: