Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, MS
Brief summary
The purpose of this study is to determine changes on overall gait as well as in multiple gait and balance parameters after withdrawal of dalfampridine-ER 10mg in MS subjects who are receiving the medication consistently for at least two weeks prior to screening.
Detailed description
Longitudinal study design
Interventions
OTHERWithdrawal of dalfampridine-ER 10mg
Withdrawal of dalfampridine-ER 10mg (7 days on study drug followed by withdrawal period of 10 days, followed by on study drug until study completion) * On drug Day-7 (visit 1) through Day 1 (visit 2) * Off drug Day 5±2 days (visit 3) through Day 11±2 days (visit 4) * On drug Day 15±2 days (visit 5)
Sponsors
Prometrika, LLC
BCS Consulting, Inc.
Acorda Therapeutics
Study design
Observational model
COHORT
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of multiple sclerosis * Receiving Ampyra® consistently for at least 2 weeks prior to the screening visit * No history of seizures except simple febrile seizures
Exclusion criteria
* Sexually active woman of childbearing potential who is not surgically sterile, \<two years post-menopause or is not using effective birth control methods * Subject who is pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Score Overall Gait After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | The co-primary efficacy variable was overall gait. This novel composite score was created from standardized individual NeuroCom test results (Z-scores). ZGAIT (Z-Score Gait) is the average of Walk Across (WA) measuring step width, step length, speed; Tandem Walk (TW) measuring step width, speed and end sway, and Step/Quick turn (SQT) measuring turn time and turn sway). Overall gait was calculated by transforming ZGAIT into a percentile using the standard normal distribution. This rescales the Z-score to a scale from 0 to 100. A higher score is indicative of better performance. |
| Composite Score Overall Balance After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | The co-primary efficacy variable was overall balance. This novel composite score was created from standardized individual NeuroCom test results (Z-scores). Overall balance is a weighted average of Sensory Organization Test (SOT) fixed surface eyes open, fixed surface eyes closed, walls moving eyes open, surface moving eyes open, surface moving eyes closed, surface and walls moving eyes open; Limits of Stability Test (LOS) measuring reaction time, movement velocity, endpoint excursion, maximum excursion and directional control; and Adaptation Test (ADT) measuring the averaged, raw sway and center of force during rotational disturbances. ZBAL (Z-Score Balance)= (ZSOT\*0.5) + (ZADT\*0.2) + (ZLOS\*0.3) Overall balance was calculated by transforming ZBAL into a percentile using the standard normal distribution. This rescales the Z-score to a scale from 0 to 100. A higher score is indicative of better performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change on the Berg's Balance Scale (BBS) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | The BBS is a 14-item scale that evaluates subjects ability to sit, stand, reach, maintain single-leg stance, and turn. The scoring is rated from 0 (cannot perform task) to 4 (normal performance of task) for each of 14 items. The maximum possible score is 56 and the lowest 0. A higher total score is indicative of better performance. |
| Change on the Two Minute Walk Test (2MWT) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | Subjects will walk without assistance for 2 minutes and the distance will be measured and timed by the use of a stop watch. A larger walking distance is indicative of better performance. |
| Change on the Timed 25 Foot Walk Test (T25FW) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11) | The T25FW test is a measure of ambulatory function that provides quantitative data and is used widely in the MS population A higher walking speed is indicative of better performance |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalfampridine-ER 10mg Subjects with MS taking dalfampridine-ER 10mg and considered to be responders
Withdrawal of dalfampridine-ER 10mg : Withdrawal of dalfampridine-ER 10mg (7 days on study drug followed by withdrawal period of 10 days, followed by on study drug until study completion) | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Dalfampridine-ER 10mg |
|---|---|
| Age Continuous | 53.1 years STANDARD_DEVIATION 10.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 20 | 5 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Composite Score Overall Balance After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
The co-primary efficacy variable was overall balance. This novel composite score was created from standardized individual NeuroCom test results (Z-scores). Overall balance is a weighted average of Sensory Organization Test (SOT) fixed surface eyes open, fixed surface eyes closed, walls moving eyes open, surface moving eyes open, surface moving eyes closed, surface and walls moving eyes open; Limits of Stability Test (LOS) measuring reaction time, movement velocity, endpoint excursion, maximum excursion and directional control; and Adaptation Test (ADT) measuring the averaged, raw sway and center of force during rotational disturbances. ZBAL (Z-Score Balance)= (ZSOT\*0.5) + (ZADT\*0.2) + (ZLOS\*0.3) Overall balance was calculated by transforming ZBAL into a percentile using the standard normal distribution. This rescales the Z-score to a scale from 0 to 100. A higher score is indicative of better performance.
Time frame: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)
Population: Full Analysis Population (FAP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine-ER Withdrawn | Composite Score Overall Balance After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 55.10 units on a scale | Standard Deviation 27.15 |
| Dalfampridine-ER 10 mg | Composite Score Overall Balance After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 54.98 units on a scale | Standard Deviation 24.16 |
Comparison: The co-primary efficacy variable was overall balance. This novel composite score was created from standardized individual NeuroCom test results (Z-scores). Overall balance was a weighted average of SOT, LOS, and ADT.p-value: 0.43495% CI: [-8.6, 3.84]Mixed Models Analysis
Primary
Composite Score Overall Gait After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
The co-primary efficacy variable was overall gait. This novel composite score was created from standardized individual NeuroCom test results (Z-scores). ZGAIT (Z-Score Gait) is the average of Walk Across (WA) measuring step width, step length, speed; Tandem Walk (TW) measuring step width, speed and end sway, and Step/Quick turn (SQT) measuring turn time and turn sway). Overall gait was calculated by transforming ZGAIT into a percentile using the standard normal distribution. This rescales the Z-score to a scale from 0 to 100. A higher score is indicative of better performance.
Time frame: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)
Population: Full Analysis Population (FAP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine-ER Withdrawn | Composite Score Overall Gait After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 46.01 units on a scale | Standard Deviation 23.716 |
| Dalfampridine-ER 10 mg | Composite Score Overall Gait After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 51.40 units on a scale | Standard Deviation 21.582 |
Comparison: The co-primary efficacy variable was overall gait. This novel composite score was created from standardized individual NeuroCom test results (Z-scores). Overall gait was the average of WA, TW, and SQT; a higher score is indicative of better performance.p-value: 0.01595% CI: [0.87, 7.2]Mixed Models Analysis
Secondary
Change on the Berg's Balance Scale (BBS) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
The BBS is a 14-item scale that evaluates subjects ability to sit, stand, reach, maintain single-leg stance, and turn. The scoring is rated from 0 (cannot perform task) to 4 (normal performance of task) for each of 14 items. The maximum possible score is 56 and the lowest 0. A higher total score is indicative of better performance.
Time frame: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)
Population: Full Analysis Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine-ER Withdrawn | Change on the Berg's Balance Scale (BBS) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 45.7 units on a scale | Standard Deviation 7.26 |
| Dalfampridine-ER 10 mg | Change on the Berg's Balance Scale (BBS) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 47.3 units on a scale | Standard Deviation 6.71 |
p-value: 0.00395% CI: [0.7, 2.8]Mixed Models Analysis
Secondary
Change on the Timed 25 Foot Walk Test (T25FW) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
The T25FW test is a measure of ambulatory function that provides quantitative data and is used widely in the MS population A higher walking speed is indicative of better performance
Time frame: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)
Population: Full Analysis Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine-ER Withdrawn | Change on the Timed 25 Foot Walk Test (T25FW) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 3.42 Feet per second (ft/s) | Standard Deviation 1.062 |
| Dalfampridine-ER 10 mg | Change on the Timed 25 Foot Walk Test (T25FW) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 3.78 Feet per second (ft/s) | Standard Deviation 0.901 |
p-value: <0.00195% CI: [0.19, 0.54]Mixed Models Analysis
Secondary
Change on the Two Minute Walk Test (2MWT) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg
Subjects will walk without assistance for 2 minutes and the distance will be measured and timed by the use of a stop watch. A larger walking distance is indicative of better performance.
Time frame: 11 days on drug (day-7 to day 1 + day 11 to day 15) and 10 days withdrawn (day 1 to day 11)
Population: Full Analysis Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalfampridine-ER Withdrawn | Change on the Two Minute Walk Test (2MWT) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 119.381 Meters | Standard Deviation 35.9033 |
| Dalfampridine-ER 10 mg | Change on the Two Minute Walk Test (2MWT) After Withdrawal and Reinitiation of Dalfampridine-ER 10mg | 129.044 Meters | Standard Deviation 28.8752 |
p-value: 0.00695% CI: [2.507, 12.95]Mixed Models Analysis