Cerebral Palsy (CP)
Conditions
Brief summary
A double-blind, placebo-controlled, crossover study in subjects with cerebral palsy (CP) to evaluate the safety and tolerability and the effect of dalfampridine extended release (ER) tablets on sensorimotor function
Interventions
OTHERPlacebo
Sponsors
Acorda Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* A diagnosis of CP * No previous use of any dalfampridine formulation * Ability to perform all the required study procedures. Subjects should be capable of fully extending and flexing both hands
Exclusion criteria
* Presence of any progressive neurological disease * Severe CP defined as the requirement to use a wheelchair at all times and a care taker for constant assistance in daily activities. This definition includes spastic quadriplegia * Pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | up to 31 days | Safety and tolerability will be assessed primarily by monitoring Treatment Emergent Adverse Events (TEAEs) TEAEs are defined as Adverse Events (AEs) with date of onset (or worsening) on or after the start-date of double-blind treatment and no more than 5 days after the last dose of double-blind treatment for Part A of the study and no more than 9 days for Part B of the study. The severity categories of mild, moderate or severe, are defined below: * Mild is defined as causing no limitation of usual activities * Moderate is defined as causing some limitation of usual activities * Severe is defined as causing inability to carry out usual activities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure the Effects of Both Single and Multiple Doses of Dalfampridine-ER 10 mg on Sensorimotor Function | up to 31 days | * Hand strength as measured by a composite Z-score derived from the grip test, and key, tip and palmar pinch tests * Manual dexterity as measured by the Box and Block Test * Walking speed as measured by the Timed 25 Foot Walk (T25FW) * Gait as measured by gait analysis equipment (to be performed by sites that have the capability to perform it) * For Part B only, subjective impressions of treatment as measured by: * Subject Global Impression (SGI) * Clinician Global Impression (CGI) |
Countries
United States
Participant flow
Pre-assignment details
Part A, 11 subjects enrolled and randomized. 6 subjects randomized into Sequence BA (placebo - dalfampridine-ER) and 5 randomized into Sequence AB (dalfampridine-ER - placebo). Part B, 24 subjects enrolled and randomized. 12 subjects randomized into Sequence BA (placebo - dalfampridine-ER) and 12 into Sequence AB (dalfampridine-ER - placebo).
Participants by arm
| Arm | Count |
|---|---|
| (PART A) Placebo Then Dalfampridine-ER 10mg Each subject randomized to the BA arm will receive a single witnessed dose of (B) placebo, and a single witnessed dose of (A) dalfampridine-ER 10 mg, two days apart
Day 1, visit 2, subjects will receive placebo. Day 3, visit 3, subjects will receive dalfampridine-ER 10mg | 6 |
| (PART A) Dalfampridine-ER 10mg Then Placebo Each subject randomized to the AB arm will receive a single witnessed dose of (A) dalfampridine-ER 10 mg, and a single witnessed dose of (B) placebo, two days apart
Day 1, visit 2, subjects will receive dalfampridine-ER 10mg. Day 3, visit 3 subjects will receive placebo | 5 |
| (PART B) Placebo Then Dalfampridine-ER 10mg Each subject randomized to the BA arm will receive multiple doses of (B) placebo, and multiple doses of (A) dalfampridine-ER 10mg
Day 1, visit 2, subjects will be given 15 tablets of placebo taken twice daily for 7 days and an additional 1 tablet for 1 day. Day 15, visit 4, subjects will be given 15 tablets dalfampridine-ER taken twice daily for 7 days and an additional 1 tablet for 1 day | 12 |
| (PART B) Dalfampridine-ER 10mg Then Placebo Each subject randomized to the AB arm will receive multiple doses of (A) dalfampridine-ER 10mg and multiple doses of (B) placebo
Day 1, visit 2, subjects will be given 15 tablets dalfampridine-ER taken twice daily for 7 days and an additional 1 dose for 1 day. Day 15, visit 4, subjects will be given 15 tablets of placebo taken twice daily for 7 days and an additional 1 tablet for 1 day | 12 |
| Total | 35 |
Baseline characteristics
| Characteristic | (PART A) Placebo Then Dalfampridine-ER 10mg | Total | (PART B) Dalfampridine-ER 10mg Then Placebo | (PART B) Placebo Then Dalfampridine-ER 10mg | (PART A) Dalfampridine-ER 10mg Then Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 33.8 years STANDARD_DEVIATION 14.29 | 37.05 years STANDARD_DEVIATION 12.99 | 36.1 years STANDARD_DEVIATION 14.04 | 41.1 years STANDARD_DEVIATION 14.25 | 37.2 years STANDARD_DEVIATION 9.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 28 Participants | 10 Participants | 11 Participants | 4 Participants |
| Sex: Female, Male Female | 4 Participants | 21 Participants | 7 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 14 Participants | 5 Participants | 6 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 11 | 2 / 11 | 6 / 24 | 9 / 24 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP)
Safety and tolerability will be assessed primarily by monitoring Treatment Emergent Adverse Events (TEAEs) TEAEs are defined as Adverse Events (AEs) with date of onset (or worsening) on or after the start-date of double-blind treatment and no more than 5 days after the last dose of double-blind treatment for Part A of the study and no more than 9 days for Part B of the study. The severity categories of mild, moderate or severe, are defined below: * Mild is defined as causing no limitation of usual activities * Moderate is defined as causing some limitation of usual activities * Severe is defined as causing inability to carry out usual activities
Time frame: up to 31 days
Population: Safety Population (Took at least one dose)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PART A: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs | 1 participants |
| PART A: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Possibly Related to Study Drug | 1 participants |
| PART A: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Severe | 0 participants |
| PART A: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | Serious TEAEs | 0 participants |
| PART A: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Leading to Withdrawal of Study Drug | 0 participants |
| PART A: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Mild | 1 participants |
| PART A: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Moderate | 0 participants |
| PART A: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Possibly Related to Study Drug | 0 participants |
| PART A: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Moderate | 0 participants |
| PART A: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Mild | 2 participants |
| PART A: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Severe | 0 participants |
| PART A: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Leading to Withdrawal of Study Drug | 0 participants |
| PART A: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | Serious TEAEs | 0 participants |
| PART A: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs | 2 participants |
| PART B: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Moderate | 1 participants |
| PART B: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs | 6 participants |
| PART B: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | Serious TEAEs | 0 participants |
| PART B: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Mild | 5 participants |
| PART B: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Severe | 0 participants |
| PART B: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Possibly Related to Study Drug | 3 participants |
| PART B: Placebo | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Leading to Withdrawal of Study Drug | 0 participants |
| PART B: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Mild | 8 participants |
| PART B: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Leading to Withdrawal of Study Drug | 0 participants |
| PART B: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Possibly Related to Study Drug | 7 participants |
| PART B: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | Serious TEAEs | 0 participants |
| PART B: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs | 9 participants |
| PART B: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Severe | 0 participants |
| PART B: Dalfampridine-ER 10mg | Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) | TEAEs Maximum Severity - Moderate | 1 participants |
Secondary
Measure the Effects of Both Single and Multiple Doses of Dalfampridine-ER 10 mg on Sensorimotor Function
* Hand strength as measured by a composite Z-score derived from the grip test, and key, tip and palmar pinch tests * Manual dexterity as measured by the Box and Block Test * Walking speed as measured by the Timed 25 Foot Walk (T25FW) * Gait as measured by gait analysis equipment (to be performed by sites that have the capability to perform it) * For Part B only, subjective impressions of treatment as measured by: * Subject Global Impression (SGI) * Clinician Global Impression (CGI)
Time frame: up to 31 days