One Year, Open Label, Dose Escalation Long-term Safety Study in Multiple Sclerosis (MS) Subjects With Spasticity

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

Inclusion Criteria:

- Patients (male or female) 18 to 70 years of age, inclusive, at the time of the first
dose.

- Have an established diagnosis (per McDonald 2005 Criteria, of Multiple Sclerosis
Appendix C (either relapsing remitting or secondary progressive course), that
manifests spasticity.

- If receiving disease-modifying medications (immunomodulatory treatment), these must
have been at a stable dose for at least one (1) months prior to screening, and the
subject must be willing to maintain this treatment for the duration of the study.

- If receiving botulinum toxin must be on a stable treatment regimen (e.g. every 12
weeks).

- If receiving phenol or alcohol injections, should have been received 60 days before
enrolment in the study.

- Absence of infections and peripheral vascular disease.

- Have a creatinine clearance, as calculated by Glomerular Filtration Rate using the
Modification of Diet in Renal Disease (MDRD) formula , greater than 60
milliliters/minute.

- Use of a medically highly effective form of birth control during the study and for 90
days thereafter for women of child-bearing potential (including female subjects and
female partners of non-sterile male subjects. .

- Willing to allow his or her general practitioner and consultant, if appropriate, to
be notified of participation in the study

Exclusion Criteria:

- 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.

- History of allergy to baclofen.

- Concomitant use of medications that would potentially interfere with the actions of
the study medication or outcome variables (Appendix D Prohibited Concomitant
Medications)

- Pregnancy, lactation or planned pregnancy during the course of the study and for
three months thereafter. (Confirmation that the subject is not pregnant must be
established by a negative serum pregnancy test at baseline).

- History of, or current unstable psychiatric disease, or signs and symptoms of
significant medical disorders such as severe, progressive, or uncontrolled renal,
hepatic, gastrointestinal, hematological, endocrine, immunologic, pulmonary, cardiac
or neurological disease which, in the opinion of the investigator, may; put the
subject at risk because of participation, influence the result of the study, or
affect the subject's ability to participate.

- Seizures requiring medication.

- Current significant cognitive deficit, severe or untreated anxiety, severe or
untreated depression.

- Subjects with abnormal micturition that requires indwelling or intermittent
catheterization or with lower urinary tract symptoms (LUTS) that result in a score
greater than twenty-six (>26) in the Baseline Urinary Symptom Profile©
questionnaire.

- Current malignancy or history of malignancy that has not been in remission for more
than five years, except effectively treated basal cell skin carcinoma.

- History of substance abuse within the past twelve (12) months.

- Participation in another interventional research study within thirty (30) days of
Screening except OS440-3002.

- Patients who are uncooperative or unwilling to sign consent form.