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

NCT ID: NCT01844232

Last Updated: 2022-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2015-01-31

Brief 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

Conditions

Multiple Sclerosis; Spasticity

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arbaclofen Extended Release (ER) Tablets

Arbaclofen Extended Release Tablets, 20 mg/day, 30 mg/day or 40 mg/day

Group Type: EXPERIMENTAL

arbaclofen

Intervention Type: DRUG

Arbaclofen ER tablets, 20 mg, 30 mg and 40 mg

Interventions

arbaclofen

Arbaclofen ER tablets, 20 mg, 30 mg and 40 mg

Intervention Type: DRUG

Other Intervention Names

OS440

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Osmotica Pharmaceutical US LLC

INDUSTRY

Sponsor Role: collaborator

RVL Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Praveen Tyle, Ph.D.

Role: STUDY_CHAIR

Osmotica Pharmaceutical

Locations

Osmotica Study Site-154

Gilbert, Arizona, United States

Osmotica Study Site-158

Phoenix, Arizona, United States

Osmotica Study Site-165

Pasadena, California, United States

Osmotica Study Site-164

Torrance, California, United States

Osomtica Study Site-164

Torrance, California, United States

Osmotica Study Site-173

Bradenton, Florida, United States

Osmotica Study Site-178

Pompano Beach, Florida, United States

Osmotica Study Site-170

Tampa, Florida, United States

Osmotica Study Site-179

Northbrook, Illinois, United States

Osmotica Study Site-174

Lenexa, Kansas, United States

Osmotica Study Site-175

Ann Arbor, Michigan, United States

Osmotica Study Site-161

Plainview, New York, United States

Osmotica Study Site-151

Charlotte, North Carolina, United States

Osmotica Study Site-157

High Point, North Carolina, United States

Osmotica Study Site-155

Raleigh, North Carolina, United States

Osmotica Study Site-152

Wilmington, North Carolina, United States

Osmotica Study Site-156

Dayton, Ohio, United States

Osmotica Study Site-163

Philadelphia, Pennsylvania, United States

Osmotica Study Site-162

Franklin, Tennessee, United States

Osmotica Study Site-171

San Antonio, Texas, United States

Osmotica Study Site-166

Vienna, Virginia, United States

Osmotica Study Site-554

Krasnoyarsk, , Russia

Osmotica Study Site-552

Krasnoyarsk, , Russia

Osmotica Study Site-557

Moscow, , Russia

Osmotica Study Site-556

Moscow, , Russia

Osmotica Study Site-553

Pyatigorsk, , Russia

Osmotica Study Site-551

Saint Petersburg, , Russia

Osmotica Study Site-560

Sestroretsk, , Russia

Osmotica Study Site-555

Tonnel'nyy, , Russia

Osmotica Study Site-653

Dnipropetrovsk, , Ukraine

Osmotica Study Site-655

Dnipropetrovsk, , Ukraine

Osmotica Study Site-651

Donetsk, , Ukraine

Osmotica Study Site-654

Kharkiv, , Ukraine

Osmotica Study Site-656

Lviv, , Ukraine

Osmotica Study Site-657

Poltava, , Ukraine

Countries

United States; Russia; Ukraine

Other Identifiers

Arbaclofen OS440-3003

Identifier Type: -

Identifier Source: org_study_id