Multiple Sclerosis
Conditions
Keywords
Ambulation
Brief summary
A randomized placebo controlled double-blind cross-over trial of Dalfampridine ER for effect on ambulatory activity in people with multiple sclerosis
Detailed description
This is a parallel-group, double-blind, randomized controlled crossover trial with a 1:1 randomization. There are two treatment periods of 4 weeks and a two-week off treatment washout period. Treatment periods are DER (dalfampridine ER) followed by placebo (group A) and placebo followed by DER (group B), respectively. All dosages will be administered twice a week. Purpose of the study is to see if using the study drug(dalfampridine Er) for a short period of time will improve the way subjects with multiple sclerosis (MS) walk.
Interventions
DRUGdalfampridine ER
dalfampridine ER 10mg bid for 4 weeks
DRUGplacebo
identical placebo tablet administered bid for four weeks
Sponsors
Acorda Therapeutics
Brown, Theodore R., M.D., MPH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of MS made at least 3 months prior to based McDonald or Proser criteria. * Age 18-75 years old inclusive. * Expanded Disability Status Scale (EDS) 0-6.5 * Clinical stability defined as no MS exacerbation or change in disease modifying therapy for 60 days prior to screening. * Screening 6-minute walking test distance between 50m-500m, inclusive. * Written informed consent.
Exclusion criteria
* use of 4-aminopyridine within 6 months of screening * Any contraindication to DER: * Allergy to DER * history of seizure disorder or history of EEG showing epileptiform activity * Renal insufficiency (estimated GFR \< 60. * Any condition that would exclude 6 minute walking testing: * Cardiac surgery or myocardial infarction within the last 3 months. * Severe aortic stenosis or hypertropic cardiomyopathy. * Pulmonary embolus or infarction in the last 6 months. * Uncontrolled hypertension by history or by screening or baseline diastolic blood pressure \> 170, or systolic blood pressure \> 105. * Use of oxygen at home for 24 hours/day or severe lung disease. * History of ventricular arrhythmia or finding of significant ventricular arrhythmia. atrial arrhythmia or 2nd or 3rd degree heart block on screening ECG. * Concomitant neurological disease, such as ALS, Parkinson Disease, stroke. * Hospitalization in the last 6 months for psychiatric illness. * Alcohol or drug abuse within the past year. * Females who are breast-feeding, pregnant or have potential to become pregnant during the course of the study( fertile and unwilling/unable to use effective contraceptive measures) * Cognitive deficits that would interfere with the subject's ability to give informed consent or preform study testing. * Any other serious and/or unstable medical condition. * Use of mitoxantrone (Novantrone) within 6 months of baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Activity Index | 10 weeks | peak activity index is a measure of the 30 fastest minutes of walking over a 24 hour period, averaged over one week of accelerometer wear. Measurement is change from baseline to 4 weeks on intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stepcount | 10 weeks | change in daily stepcount recorded by an accelerometer and averaged over 1 week of wear baseline vs 4 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalfampridine ER 10mg Bid Followed by Placebo • Age 18-75 inclusive, Male or Female 4 week administration of dalfampridine ER 10mg bid
Group A: dalfampridine ER 10mg bid for 4 weeks, 2 week washout, then matching placebo for 4 weeks | 22 |
| Placebo Followed by Dalfampridine ER 10mg Bid • Age 18-75 inclusive, Male or Female identical placebo tablet administered bid for four weeks
Group B: identical placebo tablet administered bid for four weeks, 2 week washout, then dalfampridine ER 10mg bid for 4 weeks | 21 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (28 Days) | Adverse Event | 1 | 0 |
| Second Intervention (28 Days) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Dalfampridine ER 10mg Bid Followed by Placebo | Placebo Followed by Dalfampridine ER 10mg Bid | Total |
|---|---|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 2.5 | 53.3 years STANDARD_DEVIATION 2.2 | 54.2 years STANDARD_DEVIATION 2.3 |
| Sex/Gender, Customized female patients | 19 participants | 11 participants | 30 participants |
| Sex/Gender, Customized male patients | 3 participants | 10 participants | 13 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 43 | 0 / 42 |
| serious Total, serious adverse events | 0 / 43 | 0 / 42 |
Outcome results
Primary
Peak Activity Index
peak activity index is a measure of the 30 fastest minutes of walking over a 24 hour period, averaged over one week of accelerometer wear. Measurement is change from baseline to 4 weeks on intervention
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine ER 10mg Bid | Peak Activity Index | 0.6 change in strides per minute | Standard Deviation 0.54 |
| Placebo | Peak Activity Index | 0.3 change in strides per minute | Standard Deviation 0.55 |
p-value: 0.586Mixed Models Analysis
Secondary
Stepcount
change in daily stepcount recorded by an accelerometer and averaged over 1 week of wear baseline vs 4 weeks
Time frame: 10 weeks
Population: total subject population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine ER 10mg Bid | Stepcount | 148.7 steps per day | Standard Deviation 222 |
| Placebo | Stepcount | 128 steps per day | Standard Deviation 225 |