Multiple SclerosisPhase 3NCT01844232
One Year, Open Label, Dose Escalation Long-term Safety Study in Multiple Sclerosis (MS) Subjects With Spasticity
A Phase 3 study testing arbaclofen in people with Multiple Sclerosis and Spasticity, run by RVL Pharmaceuticals, Inc. at 35 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis, Spasticity
- What is being tested?
- arbaclofen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 35 sitesin 3 countries
- Study dates
- Apr 2013to Jan 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
35 sites in 3 countries.
35 sites in 3 countries
United States21 sites
Osmotica Study Site-175
Ann Arbor, Michigan, 48104
Osmotica Study Site-173
Bradenton, Florida, 34205
Osmotica Study Site-151
Charlotte, North Carolina, 28203
Osmotica Study Site-156
Dayton, Ohio, 45417
Osmotica Study Site-162
Franklin, Tennessee, 37064
Osmotica Study Site-154
Gilbert, Arizona, 85234
Osmotica Study Site-157
High Point, North Carolina, 27262
Osmotica Study Site-174
Lenexa, Kansas, 66214
Osmotica Study Site-179
Northbrook, Illinois, 60096
Osmotica Study Site-165
Pasadena, California, 91105
Osmotica Study Site-163
Philadelphia, Pennsylvania, 19107
Osmotica Study Site-158
Phoenix, Arizona, 85032
Osmotica Study Site-161
Plainview, New York, 11803
Osmotica Study Site-178
Pompano Beach, Florida, 33060
Osmotica Study Site-155
Raleigh, North Carolina, 27607
Osmotica Study Site-171
San Antonio, Texas, 78229
Osmotica Study Site-170
Tampa, Florida, 33606
Osmotica Study Site-164
Torrance, California, 90505
Osomtica Study Site-164
Torrance, California, 90505
Osmotica Study Site-166
Vienna, Virginia, 22182
Osmotica Study Site-152
Wilmington, North Carolina, 28401
Russia8 sites
Osmotica Study Site-554
Krasnoyarsk, 660022
Osmotica Study Site-552
Krasnoyarsk
Osmotica Study Site-557
Moscow, 107150
Osmotica Study Site-556
Moscow, 127018
Osmotica Study Site-553
Pyatigorsk
Osmotica Study Site-551
Saint Petersburg, 190000
Osmotica Study Site-560
Sestroretsk, 197706
Osmotica Study Site-555
Tonnel'nyy, 357034
Ukraine6 sites
Osmotica Study Site-653
Dnipropetrovsk, 49022
Osmotica Study Site-655
Dnipropetrovsk, 53012
Osmotica Study Site-651
Donetsk, 83003
Osmotica Study Site-654
Kharkiv, 61103
Osmotica Study Site-656
Lviv, 79010
Osmotica Study Site-657
Poltava, 36011
About this study
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 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.
Read the 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
- Being tested
- arbaclofen
- Keywords
- Multiple sclerosis, spasticity, arbaclofen
- Medical subject headings
- Multiple Sclerosis, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
arbaclofenDrug
Also called OS440
Arbaclofen ER tablets, 20 mg, 30 mg and 40 mg
| Study group | Role | What they receive |
|---|---|---|
| Arbaclofen Extended Release (ER) Tablets | Experimental | Arbaclofen Extended Release Tablets, 20 mg/day, 30 mg/day or 40 mg/day Receives: Drug: arbaclofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From the beginning of dose titration to end of study (day 393 of dosing)
Secondary outcomes (1)
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)
Measured: From baseline (Day1, Visit 2) to end of treatment (Day 393)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2013 (estimated)
- Study startApr 2013
- Primary completionDec 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- RVL Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Osmotica Pharmaceutical US LLC
- Responsible party
- Sponsor
- Investigators
- Praveen Tyle, Ph.D., Study chair, Osmotica Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01844232
- Sponsor's protocol ID
- Arbaclofen OS440-3003
- Status last verified
- May 2015
- First submitted
- 24 Apr 2013
- Last updated
- 25 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01844232
- Acronym / sponsor ID
- Arbaclofen OS440-3003
- Conditions
- Multiple Sclerosis, Spasticity
- Keywords
- Multiple sclerosis, spasticity, arbaclofen
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- RVL Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Osmotica Pharmaceutical US LLC
- Study start
- Apr 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 1 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Arbaclofen Extended Release (ER) Tablets | Experimental | Drug: arbaclofenArbaclofen Extended Release Tablets, 20 mg/day, 30 mg/day or 40 mg/day |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (13 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| arbaclofenAlso: OS440Arbaclofen ER tablets, 20 mg, 30 mg and 40 mg | Drug | Arbaclofen Extended Release (ER) Tablets |
Primary outcome
Assessment of Adverse Events
Time frame: From the beginning of dose titration to end of study (day 393 of dosing)
Determination of incidence and severity of Adverse Events (AEs), discontinuations due to AEs and discontinuations due to failure of AERT to alleviate spasticity
1 secondary outcome
Determination of Change in Spasticity by Total Number-transformed Modified Ashworth Scale (TNmAS)
Time frame: From baseline (Day1, Visit 2) to end of treatment (Day 393)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Praveen Tyle, Ph.D. study chair
Osmotica Pharmaceutical
35 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing arbaclofen in people with Multiple Sclerosis and Spasticity, run by RVL Pharmaceuticals, Inc. at 35 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in United States, Russia, Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Adverse Events (time frame: From the beginning of dose titration to end of study (day 393 of dosing)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2022.