Trial Outcomes & Findings for Effect of Dalfampridine (4-AP) on Genioglossus Muscle Activity in Healthy Adults (NCT NCT02656160)

Results Overview

The EMG GG was quantified in arbitrary units derived from signal processing of the raw signal and as a percentage of wakefulness (%wake) for between-nights comparison of baseline sleep EMG GG activity. EMG GG analysis was performed on a breath-by-breath basis to identify a maximum value and a minimum value during inspiration and expiration, respectively (EMG GG peak and tonic). The difference between peak and tonic values was used to estimate respiratory related phasic activity. Wakefulness EMG GG values were obtained from a minimum of 10 epochs (30 s each) with the subject lying in the lateral position. Criteria for breath selection during wakefulness were (1) stable breathing (constant epiglottic pressure swings) and (2) absence of movement artifacts (i.e., swallowing, speech, yawns).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

1 night

Results posted on

2017-08-15

Participant Flow

Participant milestones

Participant milestones
Measure	4-AP First, Placebo Second 4-AP 10 mg administered 3 hours before normal sleep time on first study night, then a 1-week non-treatment period, then placebo-matching 4-AP administered 3 hours before normal sleep time on second study night.	Placebo First, 4-AP Second Placebo-matching 4-AP administered 3 hours before normal sleep time on first study night, then a 1-week non-treatment period, then 4-AP administered 3 hours before normal sleep time on second study night.
First Study Night STARTED	7	6
First Study Night COMPLETED	7	6
First Study Night NOT COMPLETED	0	0
Second Study Night STARTED	4	6
Second Study Night COMPLETED	4	6
Second Study Night NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Dalfampridine (4-AP) on Genioglossus Muscle Activity in Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Analyzed Participants n=10 Participants All participants who were randomized, completed both study nights, and were included in the analysis.
Age, Continuous	28 years n=93 Participants
Sex: Female, Male Female	6 Participants n=93 Participants
Sex: Female, Male Male	4 Participants n=93 Participants

PRIMARY outcome

Timeframe: 1 night

The EMG GG was quantified in arbitrary units derived from signal processing of the raw signal and as a percentage of wakefulness (%wake) for between-nights comparison of baseline sleep EMG GG activity. EMG GG analysis was performed on a breath-by-breath basis to identify a maximum value and a minimum value during inspiration and expiration, respectively (EMG GG peak and tonic). The difference between peak and tonic values was used to estimate respiratory related phasic activity. Wakefulness EMG GG values were obtained from a minimum of 10 epochs (30 s each) with the subject lying in the lateral position. Criteria for breath selection during wakefulness were (1) stable breathing (constant epiglottic pressure swings) and (2) absence of movement artifacts (i.e., swallowing, speech, yawns).

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Placebo: Placebo 3 hrs before sleep	Dalfampridine n=10 Participants Dalfampridine: Dalfampridine 10 mg extended release 3 hrs before sleep
Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration). Tonic genioglossus activity during sleep	166 percentage of wakefulness value Interval 101.0 to 333.0	136 percentage of wakefulness value Interval 90.0 to 576.0
Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration). Phasic genioglossus activity during sleep	245 percentage of wakefulness value Interval 88.0 to 428.0	163 percentage of wakefulness value Interval 109.0 to 793.0

SECONDARY outcome

Timeframe: 1 night

Effect of dalfampridine on genioglossus muscle responsiveness to increased epiglottic pressure swings during sleep in healthy controls during NREM sleep. The variation of EMG GG is expressed here as % of maximal activation.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Placebo: Placebo 3 hrs before sleep	Dalfampridine n=10 Participants Dalfampridine: Dalfampridine 10 mg extended release 3 hrs before sleep
Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O)	-0.23 %max/cmH2O Interval -0.57 to -0.09	-0.36 %max/cmH2O Interval -1.06 to -0.1

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dalfampridine

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=10 participants at risk Placebo: Placebo 3 hrs before sleep	Dalfampridine n=10 participants at risk Dalfampridine: Dalfampridine 10 mg extended release 3 hrs before sleep
Nervous system disorders Headache	0.00% 0/10 • 2 weeks	10.0% 1/10 • Number of events 1 • 2 weeks

Additional Information

Andrew Wellman, MD, PhD

Brigham and women's Hospital

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place