Long-Term Study of Arbaclofen Extended-Release Tablets in Multiple Sclerosis Patients with Spasticity

• Register: EUCTR
• Last refreshed on: 4 May 2020
• Main ID: EUCTR2017-004101-40-PL
• Date of registration: 12/02/2018
• Prospective Registration: Yes
• Primary sponsor: Osmotica Pharmaceutical US LLC
• Public title: Long-Term Study of Arbaclofen Extended-Release Tablets in Multiple Sclerosis Patients with Spasticity
• Scientific title: An Open-Label Study to Evaluate the Long-Term Safety of Arbaclofen Extended-Release Tablets in Multiple Sclerosis Patients with Spasticity (Study OS440-3005).
• Date of first enrolment: 21/03/2018
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004101-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Moldova, Republic of, Poland, Russian Federation, Serbia, Ukraine, United States

Contacts

• Name: David Jacobs
• Affiliation: Osmotica Pharmaceutical US LLC

• Name: David Jacobs
• Affiliation: Osmotica Pharmaceutical US LLC

Key inclusion & exclusion criteria

Inclusion criteria:
Male and female subjects will be considered eligible for participation in the study if all the
following inclusion criteria are satisfied at Visit 1 (Baseline).
1. Subjects 18 to 65 years of age, inclusive.
2. An established diagnosis per McDonald Criteria (Polman et al 2011) of MS (either RR or 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 puridine), 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,1 of >50 mL/minute.
9. Use of a medically highly effective form of birth control 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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 288
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion criteria:
Subjects who meet any of the following criteria will not qualify for the study.
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.
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. 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Spasticity in patients with multiple sclerosis
MedDRA version: 20.0 Level: LLT Classification code 10041416 Term: Spasticity System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Arbaclofen Extended Release Tablets
Product Code: OS440
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Arbaclofen
CAS Number: 69308-37-8
Current Sponsor code: OS440
Other descriptive name: AERT, (R)-Baclofen
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: The secondary objectives are to:
• Assess the Patient Global Impression of Change (PGIC) over 1 year.
• Assess the Total Numeric-transformed modified Ashworth Scale score of the most affected limb (TNmAS-MAL) over 1 year.
• Assess the Expanded Disability Status Scale (EDSS) over 1 year.

Main Objective: The primary objective of this study is to evaluate the long-term safety and tolerability of AERT in patients with spasticity due to MS.

Primary end point(s): Efficacy Endpoints:
Patient Global Impression of Change
Total Numeric-Transformed Modified Ashworth Scale
Expanded Disability Status Scale

Safety endpoints will be reported on the Safety population. Subjects will be reported according to the treatment they actually received. Safety assessment will be based on descriptive statistics and individual subject listings.

Timepoint(s) of evaluation of this end point: Efficacy endpoints are evaluated at baseline, Visit 4 and at the final Visit.
Safety endpoints: AEs are assessed on an ongoing basis throughout the study.

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

2017-004101-40-BG

NCT03319732

OS440-3005

Source(s) of Monetary Support

Osmotica Pharmaceutical US LLC

Ethics review

Status: Approved
Approval date: 05/03/2018
Contact: