Multiple Sclerosis
Conditions
Keywords
multiple sclerosis, MS, walking, leg strength, demyelination
Brief summary
The purpose of this study is to evaluate the safety, tolerability and activity of Fampridine-SR when administered for up to 36 additional months, or until it becomes commercially available whichever comes first, in subjects who previously participated in Acorda Therapeutics Protocol MS-F203.
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
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
* subject must have been previously enrolled in Acorda Therapeutics MS-F203 study for multiple sclerosis and received either Fampridine-SR or placebo * subject is a man or woman with clinical definite multiple sclerosis as defined by McDonald (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) * subject must be at least 18 years of age. Any subject who is now over the age of 70 must be in good overall health in the judgment of the Investigator * subject must be of adequate cognitive function, as judged by the Investigator, to understand and sign the IRB/REB-approved informed consent form prior to the performance of any study-specific procedures and is willing to comply with the required scheduling and assessments of the protocol * subjects who are women of childbearing potential, regardless of sexual activity, must have a negative urine pregnancy test at the Screening Visit.
Exclusion criteria
* women who are either pregnant or breastfeeding, and women of childbearing potential (defined as not surgically sterile or at least two years post menopausal) who are engaged in active heterosexual relations and, are not using one of the following birth control methods: tubal ligation, implantable contraception device, oral, patch, injectable or transdermal contraceptive, barrier method or sexual activity restricted to vasectomized partner. * subject discontinued prematurely from the MS-F203 study * subject has a history of seizures or has evidence of past, or possible, epileptiform activity on an EEG * subject has either a clinically significant abnormal ECG or laboratory value(s) at the Screening visit, as judged by the Investigator that would preclude entry into the study. ECG and laboratory results from Visit 6 or repeat results from Visit 7 of the MS-F203 study may be used as the baseline for the current study * subject has angina, uncontrolled hypertension, clinically significant cardiac arrhythmias, or any other clinically significant cardiovascular abnormality, as judged by the Investigator * subject has a known allergy to pyridine-containing substances or any of the inactive ingredients of the Fampridine-SR tablet (hydroxypropyl methylcellulose, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate, opadry white (tablet film coating)) * subject has received an investigational drug, except for Fampridine-SR or matching placebo under protocol MS-F203, within 30 days of the Screening Visit. Subject is scheduled to enroll in an investigational drug trial at any time during this study. * subject 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 5 years | 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 | Patients asked to complete a Subject Impression questionnaire rating his/her impression of the effects of study drug during the preceding week, specifically in regards to signs and symptoms associated with Multiple Sclerosis (MS). 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 Global Impression of Change (CGIC) | visit 1 and every clinic visit | Investigator's overall impression of the patients neurological status and general state of health related to his/her participation in the study; specifically signs and symptoms associated with MS. 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) | Screening visit, visit 6 and every 24 months thereafter | Each patient, based on their baseline neurological exam, are scored according to the EDSS The EDSS was used to grade patient disability on a scale from 0.0 (normal neurological exam) to 10.0 (death) at the Screening Visit, Visit 6, and Final Visit or Early Termination Visit if applicable. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fampridine-SR Tablets, 10mg twice daily | 269 |
| Total | 269 |
Baseline characteristics
| Characteristic | Fampridine-SR |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 256 Participants |
| Age Continuous Age (years) | 52.1 Years STANDARD_DEVIATION 8.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 251 Participants |
| Sex: Female, Male Female | 182 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 264 / 269 |
| serious Total, serious adverse events | 94 / 269 |
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 5 years
Population: Safety Population. No imputation for missing data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fampridine-SR 10mg (Twice a Day) | Summary of Treatment Emergent Adverse Events (TEAE). | Patients with Any TEAE | 264 Participants |
| Fampridine-SR 10mg (Twice a Day) | Summary of Treatment Emergent Adverse Events (TEAE). | Patients with Any Serious AE | 94 Participants |
| Fampridine-SR 10mg (Twice a Day) | Summary of Treatment Emergent Adverse Events (TEAE). | Patients with Any Possibly/Probably Related AE | 77 Participants |
| Fampridine-SR 10mg (Twice a Day) | Summary of Treatment Emergent Adverse Events (TEAE). | Patients Withdrawn due to AE | 37 Participants |
| Fampridine-SR 10mg (Twice a Day) | Summary of Treatment Emergent Adverse Events (TEAE). | Patients who Died | 4 Participants |
| Fampridine-SR 10mg (Twice a Day) | Summary of Treatment Emergent Adverse Events (TEAE). | Maximum Severity /Patients with Any Mild TEAE | 16 Participants |
| Fampridine-SR 10mg (Twice a Day) | Summary of Treatment Emergent Adverse Events (TEAE). | Maximum Severity /Patients with Any Moderate TEAE | 137 Participants |
| Fampridine-SR 10mg (Twice a Day) | Summary of Treatment Emergent Adverse Events (TEAE). | Maximum Severity /Patients with Any Severe TEAE | 111 Participants |
Secondary
Clinician Global Impression of Change (CGIC)
Investigator's overall impression of the patients neurological status and general state of health related to his/her participation in the study; specifically signs and symptoms associated with MS. 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
Population: ITT Population. No imputation for missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=248) >8-16 Weeks | 3.56 units on a scale | Standard Deviation 0.98 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=267) >0-8 Weeks | 3.38 units on a scale | Standard Deviation 0.88 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=256) >16-42 Weeks | 3.55 units on a scale | Standard Deviation 0.87 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=233) >42-68 Weeks | 3.63 units on a scale | Standard Deviation 0.99 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=215) >68-94 Weeks | 3.66 units on a scale | Standard Deviation 0.98 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=203) >94-120 Weeks | 3.59 units on a scale | Standard Deviation 0.99 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=194) >120-146 Weeks | 3.69 units on a scale | Standard Deviation 1.01 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=179) >146-172 Weeks | 3.85 units on a scale | Standard Deviation 1.02 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=167) >172-198 Weeks | 3.75 units on a scale | Standard Deviation 1.08 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=160) >198-224 Weeks | 3.93 units on a scale | Standard Deviation 1.13 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=76) >224-250 Weeks | 3.97 units on a scale | Standard Deviation 1.34 |
| Fampridine-SR 10mg (Twice a Day) | Clinician Global Impression of Change (CGIC) | (N=13) >250-276 Weeks | 3.39 units on a scale | Standard Deviation 1.12 |
Secondary
Expanded Disability Status Scale (EDSS)
Each patient, based on their baseline neurological exam, are scored according to the EDSS The EDSS was used to grade patient disability on a scale from 0.0 (normal neurological exam) to 10.0 (death) at the Screening Visit, Visit 6, and Final Visit or Early Termination Visit if applicable.
Time frame: Screening visit, visit 6 and every 24 months thereafter
Population: ITT Population. No imputation for missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fampridine-SR 10mg (Twice a Day) | Expanded Disability Status Scale (EDSS) | (N=268) Baseline | 5.78 units on a scale | Standard Deviation 1.07 |
| Fampridine-SR 10mg (Twice a Day) | Expanded Disability Status Scale (EDSS) | (N=192) >94-120 Weeks | 5.95 units on a scale | Standard Deviation 1.13 |
| Fampridine-SR 10mg (Twice a Day) | Expanded Disability Status Scale (EDSS) | (N= 148) >198-224 Weeks | 6.16 units on a scale | Standard Deviation 0.94 |
Secondary
Subject Global Impression (SGI)
Patients asked to complete a Subject Impression questionnaire rating his/her impression of the effects of study drug during the preceding week, specifically in regards to signs and symptoms associated with Multiple Sclerosis (MS). 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
Population: ITT Population. No imputation for missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=268) >0-8 Weeks | 4.85 units on a scale | Standard Deviation 1.1 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=247) >8-16 Weeks | 4.79 units on a scale | Standard Deviation 1.12 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=247) >16-42 Weeks | 4.86 units on a scale | Standard Deviation 1.19 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=230) >42-68 Weeks | 4.80 units on a scale | Standard Deviation 1.28 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=214) >68-94 Weeks | 4.95 units on a scale | Standard Deviation 1.2 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=203) >94-120 Weeks | 5.03 units on a scale | Standard Deviation 1.18 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=191) >120-146 Weeks | 5.14 units on a scale | Standard Deviation 1.14 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=182) >146-172 Weeks | 5.09 units on a scale | Standard Deviation 1.05 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=168) >172-198 Weeks | 5.13 units on a scale | Standard Deviation 1.11 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=159) >198-224 Weeks | 5.16 units on a scale | Standard Deviation 1.07 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=77) >224-250 Weeks | 5.20 units on a scale | Standard Deviation 1.01 |
| Fampridine-SR 10mg (Twice a Day) | Subject Global Impression (SGI) | (N=13) >250-276 Weeks | 5.46 units on a scale | Standard Deviation 1.13 |
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 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=265) >0-8 Weeks | 2.35 feet/second | Standard Deviation 0.96 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=242) >8-16 Weeks | 2.27 feet/second | Standard Deviation 0.95 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=249) >16-42 Weeks | 2.28 feet/second | Standard Deviation 1.02 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=222) >42-68 Weeks | 2.23 feet/second | Standard Deviation 1.1 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=204) >68-94 Weeks | 2.18 feet/second | Standard Deviation 1.05 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=190) >94-120 Weeks | 2.15 feet/second | Standard Deviation 1 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=177) >120-146 Weeks | 2.14 feet/second | Standard Deviation 1.03 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=156) >146-172 Weeks | 2.14 feet/second | Standard Deviation 0.99 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=143) >172-198 Weeks | 2.14 feet/second | Standard Deviation 1.06 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=137) >198-224 Weeks | 2.15 feet/second | Standard Deviation 1.05 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=58) >224-250 Weeks | 1.98 feet/second | Standard Deviation 1.09 |
| Fampridine-SR 10mg (Twice a Day) | Timed 25 Foot Walk (T25FW) | (N=7) >250-276 Weeks | 1.56 feet/second | Standard Deviation 0.97 |