Trial Outcomes & Findings for A Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder (NCT NCT03141086)

NCT ID: NCT03141086

Last Updated: 2021-01-05

Results Overview

The Multiple Sleep Latency Test (MSLT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. Mean sleep latency from MSLT was measured for four MSLT naps performed at scheduled timepoints (01:30, 03:30, 05:30, and 07:30). The primary efficacy variable was the mean MSLT sleep latency assessed at Day 1 and Day 2 of each treatment period.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 24 participants
• Primary outcome timeframe: Day 1 and Day 2 of each treatment period (midnight until 8:00)
• Results posted on: 2021-01-05

Participant Flow

Originally 46 subjects were planned to be enrolled in the study. However, 24 subjects were actually enrolled in the study and randomized as the study was prematurely terminated for business reasons.

Participant milestones

Measure	Group 1: LML134, Then Placebo LML134, then placebo	Group 2: Placebo, Then LML134 Placebo, then LML134
Overall Study STARTED	7	17
Overall Study COMPLETED	6	12
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Measure	Group 1: LML134, Then Placebo LML134, then placebo	Group 2: Placebo, Then LML134 Placebo, then LML134
Overall Study Study Terminated By Sponsor	1	1
Overall Study Withdrawal by Subject	0	1
Overall Study Protocol Violation	0	1
Overall Study Adverse Event	0	2

Baseline Characteristics

A Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder

Baseline characteristics by cohort

Measure	Group 1: LML134, Then Placebo n=7 Participants LML134, then placebo	Group 2: Placebo, Then LML134 n=17 Participants Placebo, then LML134	Total n=24 Participants Total of all reporting groups
Age, Continuous	44.0 Years STANDARD_DEVIATION 10.42 • n=5 Participants	39.3 Years STANDARD_DEVIATION 10.00 • n=7 Participants	40.7 Years STANDARD_DEVIATION 10.13 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	14 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Black Or African American	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized White	1 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 and Day 2 of each treatment period (midnight until 8:00)

Population: Full Analysis Set

The Multiple Sleep Latency Test (MSLT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. Mean sleep latency from MSLT was measured for four MSLT naps performed at scheduled timepoints (01:30, 03:30, 05:30, and 07:30). The primary efficacy variable was the mean MSLT sleep latency assessed at Day 1 and Day 2 of each treatment period.

Outcome measures

Measure	LML134 5mg n=20 Participants LML134 5mg	Placebo n=23 Participants Placebo
Mean Sleep Latency Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)	6.76 min Standard Deviation 4.154	4.12 min Standard Deviation 2.993

SECONDARY outcome

Timeframe: Day 1 and Day 2 of each treatment period (midnight until 8:00)

Population: Full analysis set

The Multiple Sleep Latency Test (MSLT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. Mean sleep latency from MSLT was measured for four MSLT naps performed at scheduled timepoints (01:30, 03:30, 05:30, and 07:30). The outcome measure is the mean value of Day 1 and Day 2 assessments for each timepoint.

Outcome measures

Measure	LML134 5mg n=20 Participants LML134 5mg	Placebo n=23 Participants Placebo
Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT) 01:30 (3.5 hours post dose)	8.73 min Standard Deviation 6.191	5.27 min Standard Deviation 5.065
Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT) 03:30 (5.5 hours post dose)	7.13 min Standard Deviation 5.188	4.57 min Standard Deviation 4.494
Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT) 05:30 (7.5 hours post dose)	5.18 min Standard Deviation 5.160	3.38 min Standard Deviation 3.398
Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT) 07:30 (9.5 hours post dose)	5.29 min Standard Deviation 4.772	3.25 min Standard Deviation 2.726

SECONDARY outcome

Timeframe: 0 to 34.5 hours post first treatment.

Population: Pharmacokinetic analysis set (only analyzed for LML134 treatment period - not analyzed for Placebo period)

Plasma PK concentration. Due to sparse sampling, only plasma concentrations were calculated and no PK parameter was evaluated by non-compartmental analysis.

Outcome measures

Measure	LML134 5mg n=21 Participants LML134 5mg	Placebo Placebo
Plasma PK Concentration pre-dose	0 ng/mL Standard Deviation 0	—
Plasma PK Concentration 0.25 hours post dose	0.184 ng/mL Standard Deviation 0.406	—
Plasma PK Concentration 3 hours post dose	24.1 ng/mL Standard Deviation 11.3	—
Plasma PK Concentration 12 hours post dose	6.53 ng/mL Standard Deviation 5.25	—
Plasma PK Concentration 24 hours post dose	1.31 ng/mL Standard Deviation 1.59	—
Plasma PK Concentration 34.5 hrs post 1st dose (10.5 hrs post 2nd dose)	7.55 ng/mL Standard Deviation 5.72	—

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis Set

PSG encompasses the monitoring of subjects in a sleep facility using an array of medical equipment with simultaneously recording on a multi-channel analog or digital system. PSG was performed in the study to record and evaluate various aspects of sleep.

Total time in bed is the time spent in bed during recording.

Outcome measures

Measure	LML134 5mg n=19 Participants LML134 5mg	Placebo n=23 Participants Placebo
Total Time in Bed Measured by Polysomnography (PSG)	479.9 min Standard Deviation 0.16	480.0 min Standard Deviation 0.14

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis Set

PSG encompasses the monitoring of subjects in a sleep facility using an array of medical equipment with simultaneously recording on a multi-channel analog or digital system. PSG was performed in the study to record and evaluate various aspects of sleep.

Total sleep time is the overall duration of sleep during the entire PSG recording.

Outcome measures

Measure	LML134 5mg n=19 Participants LML134 5mg	Placebo n=23 Participants Placebo
Sleep Time Measured by Polysomnography (PSG)	253.8 min Standard Deviation 102.53	294.8 min Standard Deviation 87.94

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis Set

PSG encompasses the monitoring of subjects in a sleep facility using an array of medical equipment with simultaneously recording on a multi-channel analog or digital system. PSG was performed in the study to record and evaluate various aspects of sleep.

Sleep efficiency is the percentage of time spent asleep during the entire PSG recording.

Outcome measures

Measure	LML134 5mg n=19 Participants LML134 5mg	Placebo n=23 Participants Placebo
Sleep Efficiency Measured by Polysomnography (PSG)	53.1 percentage of time Standard Deviation 21.17	61.4 percentage of time Standard Deviation 18.32

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis Set

PSG encompasses the monitoring of subjects in a sleep facility using an array of medical equipment with simultaneously recording on a multi-channel analog or digital system. PSG was performed in the study to record and evaluate various aspects of sleep.

Wake time after persistent sleep is a measure of time spent awake after a defined onset of sleep.

Outcome measures

Measure	LML134 5mg n=19 Participants LML134 5mg	Placebo n=23 Participants Placebo
Wake Time After Persistent Sleep Measured by Polysomnography (PSG)	214.9 min Standard Deviation 101.88	174.2 min Standard Deviation 87.48

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis Set

PSG encompasses the monitoring of subjects in a sleep facility using an array of medical equipment with simultaneously recording on a multi-channel analog or digital system. PSG was performed in the study to record and evaluate various aspects of sleep. Latency to onset of persistent sleep is defined as latency from Lights-Off to the first epoch (30 seconds) of 20 consecutive epochs of non-Wake.

Outcome measures

Measure	LML134 5mg n=19 Participants LML134 5mg	Placebo n=23 Participants Placebo
Latency to Onset of Persistent Sleep Measured by Polysomnography (PSG)	8.1 min Standard Deviation 8.92	11.0 min Standard Deviation 12.63

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis Set

PSG encompasses the monitoring of subjects in a sleep facility using an array of medical equipment with simultaneously recording on a multi-channel analog or digital system. PSG was performed in the study to record and evaluate various aspects of sleep.

Number of awakenings is defined as the number of times of entering wake stage after onset of sleep during the PSG recording.

Outcome measures

Measure	LML134 5mg n=19 Participants LML134 5mg	Placebo n=23 Participants Placebo
Number of Awakenings Measured by Polysomnography (PSG)	11.7 awakenings Standard Deviation 5.29	12.2 awakenings Standard Deviation 7.45

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis Set

PSG encompasses the monitoring of subjects in a sleep facility using an array of medical equipment with simultaneously recording on a multi-channel analog or digital system. PSG was performed in the study to record and evaluate various aspects of sleep.

Sleep latency to REM Sleep is defined as the time from Lights-Off to reaching the first epoch (i.e. 30 seconds) of REM sleep.

Outcome measures

Measure	LML134 5mg n=19 Participants LML134 5mg	Placebo n=23 Participants Placebo
Latency to Rapid Eye Movement (REM) Sleep Measured by Polysomnography (PSG)	89.7 min Standard Deviation 53.09	44.9 min Standard Deviation 38.05

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis set - this outcome measure was not recorded in the Polysomnography testing

PSG encompasses the monitoring of subjects in a sleep facility using an array of medical equipment with simultaneously recording on a multi-channel analog or digital system. PSG was performed in the study to record and evaluate various aspects of sleep.

Number of sleep cycles measured by Polysomnography (PSG).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 2 (10:00 until 18:00) of each treatment period

Population: Safety Analysis Set

N1: is defined by a relatively low amplitude, mixed frequency EEG. N2: is defined by the presence of sleep spindles and/or K complexes and the absence of sufficient high-amplitude, slow activity to define the presence of stage N3 sleep.

N3: is defined as an EEG with at least 20% of an epoch consisting of slow, high amplitude waveforms of .5 - 2 Hz and peak-to-peak amplitude of greater than 75mV.

REM: is defined by the concomitant appearance of relatively low amplitude, mixed frequency EEG activity and episodes of rapid eye movement. Sawtooth waves may be present. Chin EMG activity is typically low.

Outcome measures

Measure	LML134 5mg n=19 Participants LML134 5mg	Placebo n=23 Participants Placebo
Time Spent in Each Sleep Stage Measured by Polysomnography (PSG) N1	21.6 min Standard Deviation 13.95	25.1 min Standard Deviation 16.37
Time Spent in Each Sleep Stage Measured by Polysomnography (PSG) N2	145.7 min Standard Deviation 55.68	155.2 min Standard Deviation 58.84
Time Spent in Each Sleep Stage Measured by Polysomnography (PSG) N3	43.6 min Standard Deviation 32.70	51.1 min Standard Deviation 29.99
Time Spent in Each Sleep Stage Measured by Polysomnography (PSG) REM	42.9 min Standard Deviation 30.21	63.3 min Standard Deviation 26.52

Adverse Events

LML134 5mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	LML134 5mg n=21 participants at risk LML134 5mg	Placebo n=23 participants at risk Placebo
Gastrointestinal disorders Nausea	4.8% 1/21 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.	0.00% 0/23 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
Gastrointestinal disorders Vomiting	4.8% 1/21 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.	0.00% 0/23 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
Infections and infestations Viral infection	4.8% 1/21 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.	0.00% 0/23 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 1/21 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.	0.00% 0/23 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
Nervous system disorders Headache	14.3% 3/21 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.	13.0% 3/23 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
Psychiatric disorders Anxiety	4.8% 1/21 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.	0.00% 0/23 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/21 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.	4.3% 1/23 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.8% 1/21 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.	0.00% 0/23 • Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER