Trial Outcomes & Findings for Safety and Tolerability of Dalfampridine in Subjects With Cerebral Palsy (NCT NCT01468350)

Last Updated: 2014-06-24

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

up to 31 days

Results posted on

2014-06-24

Participant Flow

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).

Participant milestones

Participant milestones
Measure	(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	(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	(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	(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
(PART A) Day 1, Day 3 STARTED	6	5	0	0
(PART A) Day 1, Day 3 COMPLETED	6	5	0	0
(PART A) Day 1, Day 3 NOT COMPLETED	0	0	0	0
(PART B) Day 1, Day 15 STARTED	0	0	12	12
(PART B) Day 1, Day 15 COMPLETED	0	0	12	12
(PART B) Day 1, Day 15 NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Tolerability of Dalfampridine in Subjects With Cerebral Palsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	(PART A) Placebo Then Dalfampridine-ER 10mg n=6 Participants 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	(PART A) Dalfampridine-ER 10mg Then Placebo n=5 Participants 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	(PART B) Placebo Then Dalfampridine-ER 10mg n=12 Participants 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	(PART B) Dalfampridine-ER 10mg Then Placebo n=12 Participants 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	Total n=35 Participants Total of all reporting groups
Age, Continuous	33.8 years STANDARD_DEVIATION 14.29 • n=5 Participants	37.2 years STANDARD_DEVIATION 9.39 • n=7 Participants	41.1 years STANDARD_DEVIATION 14.25 • n=5 Participants	36.1 years STANDARD_DEVIATION 14.04 • n=4 Participants	37.05 years STANDARD_DEVIATION 12.99 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	21 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	14 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants	10 Participants n=4 Participants	28 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: up to 31 days

Population: Safety Population (Took at least one dose)

Outcome measures

Outcome measures
Measure	PART A: Placebo n=11 Participants 6 subjects randomized into Sequence BA (placebo - dalfampridine-ER) 5 subjects randomized into Sequence AB (dalfampridine-ER - placebo) A single witnessed dose of placebo and a single witnessed dose of dalfampridine-ER 10 mg, two days apart	PART A: Dalfampridine-ER 10mg n=11 Participants 6 subjects randomized into Sequence BA (placebo - dalfampridine-ER) 5 subjects randomized into Sequence AB (dalfampridine-ER - placebo) A single witnessed dose of placebo and a single witnessed dose of dalfampridine-ER 10 mg, two days apart	PART B: Placebo n=24 Participants 12 subjects randomized into Sequence BA (placebo - dalfampridine-ER) 12 subjects randomized into Sequence AB (dalfampridine-ER - placebo) Subjects received multiple doses of placebo and multiple doses of dalfampridine-ER 10mg	PART B: Dalfampridine-ER 10mg n=24 Participants 12 subjects randomized into Sequence BA (placebo - dalfampridine-ER) 12 subjects randomized into Sequence AB (dalfampridine-ER - placebo) Subjects received multiple doses of placebo and multiple doses of dalfampridine-ER 10mg
Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) TEAEs	1 participants	2 participants	6 participants	9 participants
Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) Serious TEAEs	0 participants	0 participants	0 participants	0 participants
Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) TEAEs Maximum Severity - Mild	1 participants	2 participants	5 participants	8 participants
Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) TEAEs Maximum Severity - Moderate	0 participants	0 participants	1 participants	1 participants
Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) TEAEs Maximum Severity - Severe	0 participants	0 participants	0 participants	0 participants
Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) TEAEs Possibly Related to Study Drug	1 participants	0 participants	3 participants	7 participants
Safety and Tolerability of Dalfampridine-ER 10mg in Subjects With Cerebral Palsy (CP) TEAEs Leading to Withdrawal of Study Drug	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome data not reported

Adverse Events

PART A: Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

PART A: Dalfampridine-ER 10mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

PART B: Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

PART B: Dalfampridine-ER 10mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Vice President - Clinical Development & Medical Affairs

Acorda Therapeutics, Inc.

Phone: 914-347-4300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor (Acorda) has the right to review and comment on proposed publications within a specified time frame, up to 60 days; multi-center trials require joint publication unless specifically permitted otherwise.
Publication restrictions are in place

Restriction type: OTHER

Measure	PART A: Placebo n=11 participants at risk 6 subjects randomized into Sequence BA (placebo - dalfampridine-ER) 5 subjects randomized into Sequence AB (dalfampridine-ER - placebo) A single witnessed dose of placebo and a single witnessed dose of dalfampridine-ER 10 mg, two days apart	PART A: Dalfampridine-ER 10mg n=11 participants at risk 6 subjects randomized into Sequence BA (placebo - dalfampridine-ER) 5 subjects randomized into Sequence AB (dalfampridine-ER - placebo) A single witnessed dose of placebo and a single witnessed dose of dalfampridine-ER 10 mg, two days apart	PART B: Placebo n=24 participants at risk 12 subjects randomized into Sequence BA (placebo - dalfampridine-ER) 12 subjects randomized into Sequence AB (dalfampridine-ER - placebo) Subjects received multiple doses of placebo and multiple doses of dalfampridine-ER 10mg	PART B: Dalfampridine-ER 10mg n=24 participants at risk 12 subjects randomized into Sequence BA (placebo - dalfampridine-ER) 12 subjects randomized into Sequence AB (dalfampridine-ER - placebo) Subjects received multiple doses of placebo and multiple doses of dalfampridine-ER 10mg
Nervous system disorders Headache	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	18.2% 2/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	12.5% 3/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
General disorders Fatigue	9.1% 1/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	12.5% 3/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Psychiatric disorders Insomnia	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	8.3% 2/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Gastrointestinal disorders Diarrhoea	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Injury, poisoning and procedural complications Fall	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Nervous system disorders Hypoaesthesia	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Gastrointestinal disorders Nausea	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Gastrointestinal disorders Dyspepsia	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Musculoskeletal and connective tissue disorders Joint crepitation	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Skin and subcutaneous tissue disorders Rash	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Nervous system disorders Somnolence	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days
Gastrointestinal disorders Vomiting	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/11 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	4.2% 1/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days	0.00% 0/24 • Up to 31 days Part A: up to 8 days Part B: up to 31 days