A Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS

NCT03290131 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: OS440-3004
• Study Type: interventional
• Target: 536
• Locations: 7 countries
• Sites: 30

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.

Conditions

Multiple Sclerosis; Spasticity, Muscle

Outcome Measures

Primary Outcomes (2)

• 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.

  84 days

• 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).

  84 days

Study Arms (3)

AERT 40 mg

ACTIVE COMPARATOR

40 mg Arbaclofen Extended-Release Tablets

Drug: Arbaclofen

AERT 80 mg

ACTIVE COMPARATOR

80 mg Arbaclofen Extended-Release Tablets

Drug: Arbaclofen

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Arbaclofen DRUG

Arbaclofen Extended Release Tablet

Also known as: AERT

AERT 40 mg; AERT 80 mg

Placebo DRUG

Placebo comparator

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:

• 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).

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.
• 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.

Sponsors & Collaborators

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

Study Sites (30)

Grodno Regional Clinical Hospital

Grodno, Belarus

Location

Minsk City Clinical Hospital #5

Minsk, Belarus

Location

Minsk Scientific and Practical Center of Surgery, Transplantology and Hematology

Minsk, Belarus

Location

Republican Research and Development Center for Neurology and Neurosurgery

Minsk, Belarus

Location

Vitebsk Regional Diagnostic Center

Vitebsk, Belarus

Location

University Clinical Centre of the Republic of Srpska, Clinic of Neurology

Banja Luka, Bosnia and Herzegovina

Location

University Clinical Hospital Mostar, Clinic of Neurology

Mostar, Bosnia and Herzegovina

Location

Multiprofile Hospital for Active Treatment - Pleven within the structure of Military Medical Academy, Sofia

Pleven, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Clinic of Neurological Diseases

Pleven, Bulgaria

Location

Medical Center "Rusemed" EOOD

Rousse, Bulgaria

Location

Multiprofile Hospital for Active Treatment "ACIBADEM City Clinic Tokuda Hospital", Sofia, Neurology and Sleep Medicine Clinic

Sofia, Bulgaria

Location

Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia

Sofia, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski", Sofia, Clinic of Neurology Diseases

Sofia, Bulgaria

Location

Clinical Hospital Center Osijek, Clinic of Neurology

Osijek, Croatia

Location

Clinical Hospital Center Rijeka, Department of Neurology

Rijeka, Croatia

Location

General Hospital Varazdin, Department of Neurology

Varaždin, Croatia

Location

Clinical Hospital Dubrava, Department of Neurology

Zagreb, Croatia

Location

Institute for Emergency Medicine

Chisinau, Moldova

Location

National Institute of Neurology and Neurosurgery

Chisinau, Moldova

Location

Dendryt Medical Center

Katowice, Poland

Location

Neuro-Medic

Katowice, Poland

Location

Neurology Center Krzysztof Selmaj

Lodz, Poland

Location

Medical Practice Professor K. Rejdak

Lublin, Poland

Location

MED-Polonia, Sp. z o.o. (LLC)

Poznan, Poland

Location

"MEDYK" Stanislaw Mazur Sp. z o.o. (LLC) Medical Centre

Rzeszów, Poland

Location

NeuroProtect Medical Center

Warsaw, Poland

Location

Clinical Center of Serbia

Belgrade, Serbia

Location

Clinical Hospital Center Zemun, Department of Neurology

Belgrade, Serbia

Location

Clinical Hospital Center Zvezdara

Belgrade, Serbia

Location

Clinical Center Kragujevac

Kragujevac, Serbia

Location

MeSH Terms

Conditions

Multiple Sclerosis; Muscle Spasticity

Interventions

arbaclofen placarbil

Condition Hierarchy (Ancestors)

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; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Vice President, Regulatory Affairs and Quality
• Organization: RVL Pharmaceuticals, Inc.

Regulatory@RVLpharma.com

908-809-1300

Study Officials

• David Jacobs, MD

  Vice President

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 21, 2017
• Study Start: January 28, 2018
• Primary Completion: December 3, 2018
• Study Completion: January 2, 2019
• Last Updated: July 15, 2022
• Results First Posted: July 15, 2022

Record last verified: 2022-05

Locations

PL (7); BE (5); BU (6); BO (2); CR (4); MO (2); SE (4)