One Year, Open Label, Dose Escalation Long-term Safety Study in Multiple Sclerosis (MS) Subjects With Spasticity
Condition: Multiple Sclerosis; Spasticity
MeSH terms: Muscle Spasticity; Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 3

Summary: 
      Clinical protocol OS440-3003 is a multicenter, open-label, non-randomized, uncontrolled, dose
      escalation study to evaluate the safety and tolerability of Arbaclofen Extended Release
      Tablets over 1 year in Multiple Sclerosis (MS) subjects with spasticity. All subjects in this
      study will receive arbaclofen in the extended release tablet formulation.
    

Detailed description: 
      Clinical protocol OS440-3003 is a multicenter, open-label, non-randomized, uncontrolled, dose
      escalation study to evaluate the safety and tolerability of Arbaclofen Extended Release
      Tablets (AERT) over 1 year in MS subjects with spasticity. All subjects in this study will
      receive arbaclofen in the extended release tablet formulation.

      All subjects will begin treatment with arbaclofen at 20 milligrams (mg) per day (2 X 10 mg)
      for two weeks, then increase to 30 mg per day (2 X 15 mg) for two weeks, and then increase to
      40 mg per day (2 X 20 mg) based on the Dose Escalation Criteria. Once the subject reaches the
      Maintenance Dose, they will remain on that dose for approximately 1 year. The Maintenance
      Dose is the highest tolerated dose, not to exceed 40 mg per day.

      In this study, the Up Titration Period begins with Visit 2 and ends when the Maintenance Dose
      is determined. The Maintenance Period is the time from establishment of the Maintenance Dose
      until the down-titration visit. For subjects that complete the study, the Maintenance Period
      is for approximately 1 year in duration. The Down Titration Period will be 2 weeks for
      subjects on the maintenance dose of 40 mg per day and 1 week for subjects on the maintenance
      dose of 30 mg per day. There is no down titration phase for subjects on a 20 mg per day
      maintenance dose.

      Subjects for whom the Maintenance Dose is 20 mg per day (i.e., subjects who did not tolerate
      the 30 mg/ day dose) will begin the 1 year Maintenance Period at Visit 4 and complete the
      study at Visit 8. Subjects for whom the Maintenance Dose is either 30 mg or 40 mg per day
      will begin the Maintenance Period at Visit 5 and complete the maintenance portion of the
      study at Visit 9.

      The next portion of the study is down titration. The subjects on the 20 mg per day
      Maintenance Dose will not have a down-titration. For subjects on the 30 mg per day
      Maintenance Dose, down-titration will begin at Visit 9 and continue for 1 week. These
      subjects will return for Visit 10 after the 1 week down-titration. For subjects on the 40 mg
      per day Maintenance Dose, down titration will begin at Visit 9 and continue for 2 weeks.
      These subjects will return for Visit 10 after the 2 week down-titration.

      Study visits will occur every two weeks until the Maintenance Dose is reached and then study
      visits will occur every three months with telephone follow-up calls monthly in between visits
    

Intervention name(s): arbaclofen
Intervention type(s): Drug
Intervention description(s): Arbaclofen ER tablets, 20 mg, 30 mg and 40 mg
Other intervention name(s): OS440
Intervention model: Sequential Assignment
Intervention model description: All subjects will begin treatment with arbaclofen at 20 milligrams (mg) per day (2 X 10 mg) for two weeks, then increase to 30 mg per day (2 X 15 mg) for two weeks, and then increase to 40 mg per day (2 X 20 mg) based on the Dose Escalation Criteria. Once the subject reaches the Maintenance Dose, they will remain on that dose for approximately 1 year. The Maintenance Dose is the highest tolerated dose, not to exceed 40 mg per day.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple sclerosis; spasticity; arbaclofen