A Study to Evaluate the Long-term Safety of Arbaclofen Extended-Release Tablets for Patients With Spasticity Due to MS

NCT03319732 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: OS440-3005
• Study Type: interventional
• Target: 323
• Locations: 1 country
• Sites: 1

Brief Summary

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 (1)

• Number of Participants With Adverse Events, Change in Vital Signs, Clinical Laboratory Test Results, 12-lead ECGs, USP Questionnaire, and C-SSRS Results

  Safety and tolerability will be assessed by the monitoring of adverse events volunteered, observed, and elicited by general questions in a non-suggestive manner. Changes in vital signs, clinical laboratory test results, 12-lead ECGs, the urinary symptom profile (USP) questionnaire, and the C-SSRS results will also be assessed.

  over 1 year

Secondary Outcomes (3)

• Patient Global Impression of Change (PGIC)

  week 60

• Total Numeric-transformed Modified Ashworth Scale Score or the Most Affected Limb (TNmAS-MAL)

  week 28

• Expanded Disability Status Scale (EDSS)

  week 60

Study Arms (1)

AERT 80 mg

EXPERIMENTAL

Arbaclofen extended release tablet, 20 mg

Drug: Arbaclofen

Interventions

Arbaclofen DRUG

Arbaclofen is the active R enantiomer of baclofen.

Also known as: AERT

AERT 80 mg

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 per McDonald Criteria (Polman et al 2011) of MS (either relapsing-remitting \[RR\] or secondary-progressive \[SP\] course) that manifests a documented history of spasticity for at least 6 months prior to Baseline.

You may not qualify if:

• Is willing to continue on open-label treatment with AERT as described in this protocol.
• 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 Baseline, and the subject must be willing to maintain this treatment dose for the duration of the study. If receiving AMPYRA® (dalfampridine, fampridine, 4 amino pyridine), subject must be at a stable dose for at least 3 months prior to Baseline.
• Stable regimen for at least 1 month prior to Baseline for all medications and non pharmacological therapies that are intended to alleviate spasticity.
• a. De novo subjects being considered for enrollment and taking medications indicated for the treatment of spasticity (ie, baclofen, benzodiazepines, cannabinoids, carisoprodol, dantrolene, tizanidine, cyclobenzaprine, any neuroleptic, ropinoprole, tolperisone, and clonidine) must wash out from these medications for a minimum of 21 days by Baseline in order to be eligible for study treatment. De novo subjects found not to meet this criterion will be withdrawn from the study and will be considered screen failures.
• Absence of infections, peripheral vascular disease, painful contractures, advanced arthritis, or other conditions that hinder evaluation of joint movement.
• Creatinine clearance, as calculated by the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease Study (MDRD) formula, of \>50 mL/minute.
• Use of a medically highly effective form of birth control (see Section 7.8 of the protocol) during the study and for 3 months thereafter for women of child-bearing potential (including female subjects).
• Willing to sign the informed consent form (ICF).
• 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.
• Use of high dose oral or intravenous methylprednisolone, or equivalent, within 3 months before Baseline.
• History of allergy to baclofen or any inactive components of the test formulation.
• Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables (Appendix 5).
• Pregnancy, lactation, or planned pregnancy during the course of the study and for 3 months after the final study visit.
• Recent history (within past 12 months) of any unstable psychiatric disease (or yes response to questions 1 or 2 on the Columbia Suicide Severity Rating Scale \[C SSRS\] at baseline), 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.

Sponsors & Collaborators

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

Study Sites (1)

Neuro Pain Medical Center

Fresno, California, 93710, United States

Location

Related Publications (1)

• Okuda DT, Kantor D, Jaros M, deVries T, Hunter S. Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study. Brain Commun. 2023 Feb 7;5(1):fcad026. doi: 10.1093/braincomms/fcad026. eCollection 2023.

  PMID: 36861013 DERIVED

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
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: October 24, 2017
• Study Start: April 3, 2018
• Primary Completion: January 27, 2020
• Study Completion: June 11, 2020
• Last Updated: August 9, 2022
• Results First Posted: July 15, 2022

Record last verified: 2022-02

Locations

US (1)