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

Multiple Sclerosis Clinical Trial

Official title:

A One Year, Open Label, Dose Escalation Study To Evaluate the Long-Term Safety of Arbaclofen Extended Release Tablets (AERT) in Multiple Sclerosis Subjects With Spasticity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01844232
• Other study ID #: Arbaclofen OS440-3003
• Status: Completed
• Phase: Phase 3
• Start date: April 2013
• Est. completion date: January 2015

Study information

• Verified date: May 2015
• Source: RVL Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: January 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Muscle Spasticity
• Sclerosis
• Spasticity

Intervention

Drug:
• arbaclofen
Arbaclofen ER tablets, 20 mg, 30 mg and 40 mg

Locations

Country	Name	City	State
Russian Federation	Osmotica Study Site-552	Krasnoyarsk
Russian Federation	Osmotica Study Site-554	Krasnoyarsk
Russian Federation	Osmotica Study Site-556	Moscow
Russian Federation	Osmotica Study Site-557	Moscow
Russian Federation	Osmotica Study Site-553	Pyatigorsk
Russian Federation	Osmotica Study Site-560	Sestroretsk
Russian Federation	Osmotica Study Site-551	St. Petersburg
Russian Federation	Osmotica Study Site-555	Tonnel'nyy
Ukraine	Osmotica Study Site-653	Dnipropetrovsk
Ukraine	Osmotica Study Site-655	Dnipropetrovsk
Ukraine	Osmotica Study Site-651	Donetsk
Ukraine	Osmotica Study Site-654	Kharkov
Ukraine	Osmotica Study Site-656	Lviv
Ukraine	Osmotica Study Site-657	Poltava
United States	Osmotica Study Site-175	Ann Arbor	Michigan
United States	Osmotica Study Site-173	Bradenton	Florida
United States	Osmotica Study Site-151	Charlotte	North Carolina
United States	Osmotica Study Site-156	Dayton	Ohio
United States	Osmotica Study Site-162	Franklin	Tennessee
United States	Osmotica Study Site-154	Gilbert	Arizona
United States	Osmotica Study Site-157	High Point	North Carolina
United States	Osmotica Study Site-174	Lenexa	Kansas
United States	Osmotica Study Site-179	Northbrook	Illinois
United States	Osmotica Study Site-165	Pasadena	California
United States	Osmotica Study Site-163	Philadelphia	Pennsylvania
United States	Osmotica Study Site-158	Phoenix	Arizona
United States	Osmotica Study Site-161	Plainview	New York
United States	Osmotica Study Site-178	Pompano Beach	Florida
United States	Osmotica Study Site-155	Raleigh	North Carolina
United States	Osmotica Study Site-171	San Antonio	Texas
United States	Osmotica Study Site-170	Tampa	Florida
United States	Osmotica Study Site-164	Torrance	California
United States	Osomtica Study Site-164	Torrance	California
United States	Osmotica Study Site-166	Vienna	Virginia
United States	Osmotica Study Site-152	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
RVL Pharmaceuticals, Inc.	Osmotica Pharmaceutical US LLC

Countries where clinical trial is conducted

United States,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Adverse Events	Determination of incidence and severity of Adverse Events (AEs), discontinuations due to AEs and discontinuations due to failure of AERT to alleviate spasticity	From the beginning of dose titration to end of study (day 393 of dosing)
Secondary	Determination of Change in Spasticity by Total Number-transformed Modified Ashworth Scale (TNmAS)	Change in the total Numeric-transformed Modified Ashworth Scale from baseline to the end of the study (Day 393)	From baseline (Day1, Visit 2) to end of treatment (Day 393)