Arbaclofen Extended-Release Tablets for Treatment of Spasticity in Patients with Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2017-004100-22-PL
• Date of registration: 09/02/2018
• Prospective Registration: Yes
• Primary sponsor: Osmotica Pharmaceutical US LLC
• Public title: Arbaclofen Extended-Release Tablets for Treatment of Spasticity in Patients with Multiple Sclerosis
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled Parallel Group Study to Investigate the Safety and Efficacy of Arbaclofen Extended-Release Tablets for the Treatment of Spasticity in Patients with Multiple Sclerosis (Study OS440-3004)
• Date of first enrolment: 21/03/2018
• Target sample size: 510
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004100-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• 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 (Screening).
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 screening.
3. Spasticity due to MS as shown by a TNmAS-MAL score =2.
4. Expanded Disability Status Scale (EDSS) score =3.0.
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 Visit 1 (Screening), 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 Visit 1 (Screening).
6. Stable regimen for at least 3 months prior to Visit 2 (Baseline) for all medications and non-pharmacological therapies that are intended to alleviate spasticity.
a. Subjects taking medications indicated for the treatment of spasticity (eg, baclofen,benzodiazepines, cannabinoids, carisoprodol, dantrolene, tizanidine, cyclobenzaprine, any neuroleptic, ropinoprole, tolperisone, and clonidine) at Visit 1 (Screening) must wash out from these medications for at most 21 days by Visit 2 (Baseline) in order to be eligible for randomization (see Section 7.7 for washout periods for specific medications). 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, of >50 mL/minute.
9. Use of a medically highly effective form of birth control (see Section 7.8) during the study and for 3 months thereafter for women of child-bearing potential (including female subjects and female partners of non-sterile male subjects). Use of a medically highly effective form of birth control (see Section 7.8) during the study and for 3 months thereafter for any subject whose partner is not sterilized or post menopausal.
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 490
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

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. Acute MS exacerbation/relapse requiring treatment or disease modifying drug dose alteration within 3 months of Visit 1 (Screening).
4. Use of high dose (120 mg daily) oral or intravenous methylprednisolone, or equivalent, within 3 months before Visit 1 (Screening).
5. Concomitant use of medications that would potentially interfere with the actions of the study medication or outcome variables.
6. Use of botulinum toxin A or B for spasticity within 6 months of Visit 1 (Screening).
7. Pregnancy, lactation, or planned pregnancy during the course of the study and for 3 months after the final study visit.
8. Recent history (within past 12 months) of any unstable psychiatric disease (or any yes response to questions 1 or 2 on the Columbia–Suicide Severity Rating Scale [C-SSRS] at Screening), 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.
9. History of epilepsy.
10. Current significant cognitive deficit, severe or untreated anxiety, severe or untreated depression.
11. 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 Visit 2 (Baseline) Urinary Symptom Profile – USP© (USP) questionnaire. Subjects who are proficient in selfcatheterization may be included in the study at investigator discretion.
12. Subject has clinically significant abnormal laboratory values, in the opinion of the investigator, at Visit 1 (Screening).
13. Current malignancy or history of malignancy that has not been in remission for more than 5 years, except effectively treated basal cell skin carcinoma.
14. Any other significant disease, disorder, or significant laboratory finding 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.
15. Planned elective surgery or other procedures requiring general anesthesia during the course of the study.
16. History of any illicit substance abuse (eg, alcohol, cocaine) or prescription for long-acting opioids within the past 12 months (tramadol use will be allowed).
17. Participation in another clinical research study within 1 month of Visit 1 (Screening).


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-
Pharmaceutical form of the placebo: Prolonged-release tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to demonstrate the safety and efficacy of Arbaclofen Extended-Release Tablets (AERT) for treatment of spasticity in patients with Multiple Sclerosis (MS)

Timepoint(s) of evaluation of this end point: Day 84

Primary end point(s): Co-Primary Efficacy Endpoints:

The AERT 40 mg dose will be compared with placebo first (for both TNmAS-MAL and CGIC). If both comparisons are significant at the 0.05 level then the AERT 80 mg dose will be tested at the 0.05 level (both TNmAS-MAL and CGIC). Both co-primary efficacy endpoints need to meet the 0.05 level for the AERT 40 mg dose comparison with placebo for the study to be considered a success. Therefore, no adjustment for multiplicity is needed. The Day 84 comparison is the primary time point for both co-primary endpoints.

Secondary Objective: Not applicable

Secondary Outcome(s)

Secondary end point(s): Secondary Efficacy Endpoints

Secondary efficacy endpoints include:
?* EDSS
?* PGIC
?* TNmAS – Total Limbs

Timepoint(s) of evaluation of this end point: Pairwise comparisons between the AERT doses and placebo will be provided at each visit where data are collected.
?* EDSS – assessed at screening, baseline and final visits
?* PGIC – assessed at final visit
?* TNmAS – assessed at screening, baseline, Visit 4, Visit 5 and final visits

Secondary ID(s)

NCT03290131

2017-004100-22-BG

OS440-3004

Source(s) of Monetary Support

Osmotica Pharmaceutical US LLC

Ethics review

Status: Approved
Approval date:
Contact: