Multiple Sclerosis
Conditions
Keywords
multiple sclerosis, MS, walking, leg strength, demyelination
Brief summary
The purpose of the study is to evaluate the safety, tolerability and activity of Fampridine-SR when administered for up to 36 additional months in patients who previously participated in the MS-F204 study or until it becomes commercially available, whichever comes first.
Detailed description
Multiple sclerosis (MS) is a disorder of the body's immune system that affects the central nervous system (CNS). Normally, nerve fibers carry electrical impulses through the spinal cord, providing communication between the brain and the arms and legs. In people with MS, the fatty sheath that surrounds and insulates the nerve fibers (called myelin) deteriorates, causing nerve impulses to be slowed or stopped. As a result, patients with MS may experience periods of muscle weakness and other symptoms such as numbness, loss of vision, loss of coordination, paralysis, spasticity, mental and physical fatigue and a decrease in the ability to think and/or remember. These periods of illness may come (exacerbations) and go (remissions). Fampridine-SR is an experimental drug that has been reported to possibly improve muscle strength and walking ability for some people with MS. This study will evaluate the effects and possible risks of taking Fampridine-SR in MS patients over a long period of time.
Interventions
DRUGFampridine-SR
Tablets, 10 mg, BID (twice daily)
Sponsors
Acorda Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patient must have been previously enrolled in the Acorda Therapeutics MS-F204 study and received either Fampridine-SR or placebo * Patient with clinically defined multiple sclerosis (the diagnostic criteria based on: McDonald WI, et al. Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Annals of Neurology. 2001; 50: 121-127) * Patient must be at least 18 years of age. Any patient who is now over the age of 70 must be in good overall health in the judgment of the investigator * Patient must be of adequate cognitive function, as judged by the Investigator * Patients who are women of childbearing potential must have a negative urine pregnancy test at the screening visit
Exclusion criteria
* Female patients who are either pregnant or breastfeeding. * Women of childbearing potential who are not using a specified birth control method * Patients discontinued prematurely from the MS-F204 study * Patients with a history of seizures or with evidence of past, or possible epileptiform activity on an EEG * Patient with either a clinically significant abnormal ECG or laboratory values at the MS-F204 EXT screening visit * Patient with severe renal impairment * Patient with angina, uncontrolled hypertension, clinically significant cardiac arrhythmias, or any other clinically significant cardiovascular abnormality, as judged by the Investigator * Patient with a known allergy to pyridine-containing substances or any of the inactive ingredients of the Fampridine-SR tablet * Patient who has received an investigational drug (other than Fampridine-SR or placebo under MS-F204 study) within 30 days of the MS-F204EXT screening visit or a patient who is scheduled to enroll in an investigational drug trial at any time during this study * Patient who has a history of drug or alcohol abuse within the past year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Treatment Emergent Adverse Events (TEAE). | up to 40 months | All adverse events reported were treatment emergent. Therefore, events that had a date of onset, or worsening, on or after the start of the open-label drug and up to 14 days after the last dose (for non-serious events) or up to 30 days after the last dose (for SAEs) were summarized. Any abnormal clinically significant changes in physical examination, medical history, clinical laboratory testing, 12-lead ECG, and standard EEG testing were captured as adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Timed 25-Foot Walk (T25FW) | Week 2, 14, 26, continuing every 26 weeks until the Final Visit | — |
| Subject Global Impression (SGI) | Visit 1 and every clinic visit thereafter (other than the follow-up visit) | For the SGI, the potential responses to the effects of the investigational drug during the preceding week were 1=terrible, 2=unhappy, 3=mostly dissatisfied, 4=neutral/ mixed, 5=mostly satisfied, 6=pleased, and 7=delighted. |
| Clinician's Global Impression (CGI) | Visit 1 and every clinic visit thereafter | The potential responses were 1=very much improved, 2=much improved, 3=somewhat improved, 4=no change, 5=somewhat worse, 6=much worse, and 7=very much worse. |
| Expanded Disability Status Scale (EDSS) | The Screening Visit, Visit 6, Final Visit or Early Termination Visit (if applicable) | The EDSS was used to grade patient disability on a scale from 0.0 (normal neurological exam) to 10.0 (death) |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fampridine-SR Tablets, 10 mg, BID | 214 |
| Total | 214 |
Baseline characteristics
| Characteristic | Fampridine-SR |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 201 Participants |
| Age Continuous | 52.0 years STANDARD_DEVIATION 9.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 201 Participants |
| Sex: Female, Male Female | 144 Participants |
| Sex: Female, Male Male | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 205 / 214 |
| serious Total, serious adverse events | 39 / 214 |
Outcome results
Primary
Summary of Treatment Emergent Adverse Events (TEAE).
All adverse events reported were treatment emergent. Therefore, events that had a date of onset, or worsening, on or after the start of the open-label drug and up to 14 days after the last dose (for non-serious events) or up to 30 days after the last dose (for SAEs) were summarized. Any abnormal clinically significant changes in physical examination, medical history, clinical laboratory testing, 12-lead ECG, and standard EEG testing were captured as adverse events.
Time frame: up to 40 months
Population: Safety Population. No imputation for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fampridine-SR | Summary of Treatment Emergent Adverse Events (TEAE). | Patients with Any TEAE | 205 participants |
| Fampridine-SR | Summary of Treatment Emergent Adverse Events (TEAE). | Patients with Any Serious TEAE | 39 participants |
| Fampridine-SR | Summary of Treatment Emergent Adverse Events (TEAE). | Patients with Any Treatment-Related AE | 46 participants |
| Fampridine-SR | Summary of Treatment Emergent Adverse Events (TEAE). | Patients Withdrawn due to AE | 7 participants |
| Fampridine-SR | Summary of Treatment Emergent Adverse Events (TEAE). | Patients who Died | 1 participants |
| Fampridine-SR | Summary of Treatment Emergent Adverse Events (TEAE). | Maximum Severity/Paitents with Any TEAE - Mild | 29 participants |
| Fampridine-SR | Summary of Treatment Emergent Adverse Events (TEAE). | Maximum Severity/Patients with Any TEAE - Moderate | 120 participants |
| Fampridine-SR | Summary of Treatment Emergent Adverse Events (TEAE). | Maximum Severity/Patients with Any TEAE - Severe | 56 participants |
Secondary
Clinician's Global Impression (CGI)
The potential responses were 1=very much improved, 2=much improved, 3=somewhat improved, 4=no change, 5=somewhat worse, 6=much worse, and 7=very much worse.
Time frame: Visit 1 and every clinic visit thereafter
Population: ITT Population. No imputation for missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=213) >0-8 Weeks | 3.38 1-7 scale rating | Standard Deviation 0.84 |
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=202) >8-16 Weeks | 3.27 1-7 scale rating | Standard Deviation 0.9 |
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=208) >16-42 Weeks | 3.48 1-7 scale rating | Standard Deviation 0.98 |
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=181) >42-68 Weeks | 3.42 1-7 scale rating | Standard Deviation 0.92 |
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=172) >68-94 Weeks | 3.58 1-7 scale rating | Standard Deviation 1.14 |
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=168) >94-120 Weeks | 3.66 1-7 scale rating | Standard Deviation 1.19 |
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=154) >120-146 Weeks | 3.65 1-7 scale rating | Standard Deviation 1.16 |
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=35) >146-172 Weeks | 3.96 1-7 scale rating | Standard Deviation 1.17 |
| Fampridine-SR | Clinician's Global Impression (CGI) | (N=2) >172-198 Weeks | 2.50 1-7 scale rating | Standard Deviation 0.71 |
Secondary
Expanded Disability Status Scale (EDSS)
The EDSS was used to grade patient disability on a scale from 0.0 (normal neurological exam) to 10.0 (death)
Time frame: The Screening Visit, Visit 6, Final Visit or Early Termination Visit (if applicable)
Population: ITT Population. No imputation for missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fampridine-SR | Expanded Disability Status Scale (EDSS) | (N=213) Baseline | 5.64 0-10 rating scale | Standard Deviation 1.11 |
| Fampridine-SR | Expanded Disability Status Scale (EDSS) | (N=163) >94-120 Weeks | 5.86 0-10 rating scale | Standard Deviation 1.05 |
Secondary
Subject Global Impression (SGI)
For the SGI, the potential responses to the effects of the investigational drug during the preceding week were 1=terrible, 2=unhappy, 3=mostly dissatisfied, 4=neutral/ mixed, 5=mostly satisfied, 6=pleased, and 7=delighted.
Time frame: Visit 1 and every clinic visit thereafter (other than the follow-up visit)
Population: ITT Population. No imputation for missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fampridine-SR | Subject Global Impression (SGI) | (N=214) >0-8 Weeks | 4.67 1-7 scale rating | Standard Deviation 1.15 |
| Fampridine-SR | Subject Global Impression (SGI) | (N=200) >8-16 Weeks | 4.70 1-7 scale rating | Standard Deviation 1.28 |
| Fampridine-SR | Subject Global Impression (SGI) | (N=199) >16-42 Weeks | 4.77 1-7 scale rating | Standard Deviation 1.29 |
| Fampridine-SR | Subject Global Impression (SGI) | (N=183) >42-68 Weeks | 5.04 1-7 scale rating | Standard Deviation 1.19 |
| Fampridine-SR | Subject Global Impression (SGI) | (N=173) >68-94 Weeks | 4.95 1-7 scale rating | Standard Deviation 1.2 |
| Fampridine-SR | Subject Global Impression (SGI) | (N=167) >94-120 Weeks | 4.97 1-7 scale rating | Standard Deviation 1.27 |
| Fampridine-SR | Subject Global Impression (SGI) | (N=153) >120-146 Weeks | 5.15 1-7 scale rating | Standard Deviation 1.11 |
| Fampridine-SR | Subject Global Impression (SGI) | (N=35) >146-172 Weeks | 4.94 1-7 scale rating | Standard Deviation 1.39 |
| Fampridine-SR | Subject Global Impression (SGI) | (N=2) >172-198 Weeks | 5.50 1-7 scale rating | Standard Deviation 0.71 |
Secondary
Timed 25-Foot Walk (T25FW)
Time frame: Week 2, 14, 26, continuing every 26 weeks until the Final Visit
Population: ITT Population. No imputation for missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=172) >42-68 Weeks | 2.46 feet/seconds | Standard Deviation 1.02 |
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=209) >0-8 Weeks | 2.60 feet/seconds | Standard Deviation 0.86 |
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=197) >8-16 Weeks | 2.53 feet/seconds | Standard Deviation 0.93 |
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=201) >16-42 Weeks | 2.52 feet/seconds | Standard Deviation 0.96 |
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=160) >68-94 Weeks | 2.37 feet/seconds | Standard Deviation 1.04 |
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=151) >94-120 Weeks | 2.35 feet/seconds | Standard Deviation 1.1 |
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=143) >120-146 Weeks | 2.27 feet/seconds | Standard Deviation 1.06 |
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=33) >146-172 Weeks | 2.17 feet/seconds | Standard Deviation 1.07 |
| Fampridine-SR | Timed 25-Foot Walk (T25FW) | (N=2) >172-198 Weeks | 1.85 feet/seconds | Standard Deviation 0.56 |