A Study to Evaluate the Long-term Safety of Arbaclofen Extended-Release Tablets for Patients With Spasticity Due to MS
Condition: Multiple Sclerosis; Spasticity, Muscle
MeSH terms: Muscle Spasticity; Multiple Sclerosis; Sclerosis
Intervention: Arbaclofen
Intervention description: Arbaclofen is the active R enantiomer of baclofen.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 323.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects 18 to 65 years of age, inclusive.

          2. 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.

          3. Has participated in Study OS440-3004 or is a new US subject (ie, a de novo subject)
             who fulfills the inclusion/exclusion criteria.

          4. Is willing to continue on open-label treatment with AERT as described in this
             protocol.

          5. 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.

          6. 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.

          7. Absence of infections, peripheral vascular disease, painful contractures, advanced
             arthritis, or other conditions that hinder evaluation of joint movement.

          8. 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.

          9. 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).

         10. Willing to sign the informed consent form (ICF).

        Exclusion Criteria:

          1. Any concomitant disease or disorder that has symptoms of spasticity or that may
             influence the subject's level of spasticity.

          2. Inability to rate their level of spasticity or distinguish it from other MS symptoms.

          3. Use of high dose oral or intravenous methylprednisolone, or equivalent, within 3
             months before Baseline.

          4. History of allergy to baclofen or any inactive components of the test formulation.

          5. Concomitant use of medications that would potentially interfere with the actions of
             the study medication or outcome variables (Appendix 5).

          6. Pregnancy, lactation, or planned pregnancy during the course of the study and for 3
             months after the final study visit.

          7. 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.

          8. History of epilepsy.

          9. Current significant cognitive deficit, severe or untreated anxiety, severe or
             untreated depression.

         10. Subjects with abnormal micturition that requires indwelling or intermittent
             catheterization or with lower urinary tract symptoms (LUTS) that result in a score >26
             in the Baseline Urinary Symptom Profile - USP© (USP) questionnaire (Appendix 6).
             Subjects who are proficient in self-catheterization may be included in the study at
             the investigator's discretion.

         11. Current malignancy or history of malignancy that has not been in remission for more
             than 5 years, except effectively treated basal cell skin carcinoma.

         12. Subject has clinically significant abnormal laboratory values, in the opinion of the
             investigator at Baseline (at Visit 6 for rollover subjects).

         13. Any other significant disease, disorder, or significant laboratory finding, including
             clinically significant abnormal laboratory values or ongoing serious adverse events
             (SAEs) at Visit 6 (Final Visit) of Study OS440-3004, 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.

         14. Planned elective surgery or other procedures requiring general anesthesia during the
             course of the study.

         15. History of any illicit substance abuse (eg, alcohol, marijuana, cocaine) or
             prescription for long-acting opioids within the past 12 months (tramadol use will be
             allowed).

         16. Participation in another clinical research study (with the exception of Study
             OS440-3004) within 1 month of Baseline.