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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03141086
• Collaborator: (none)
• Enrollment: 24
• Locations: 8
• Arms: 2
• Actual Duration (Months): 13.6
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study was to demonstrate that LML134 can increase wakefulness compared to placebo in patients with shift work disorder (SWD) measured by objective and subjective endpoints of wakefulness, i.e. the sleep latency in the multiple sleep latency test (MSLT) and the Karolinska Sleepiness Scale (KSS), respectively. Safety and PK of LML134 were also evaluated. In addition, novel methodologies to measure wakefulness and sleep were also to be tested and compared to gold standard methods like the MSLT and polysomnography (PSG) (at sites where staff have appropriate equipment and training). The aim of such comparisons was to evaluate the usefulness of the new technologies in clinical studies and provide preliminary validation data.

This was a randomized, subject and investigator-blinded, placebo controlled, crossover, multi-center Proof of Concept (PoC) study with in-house simulated laboratory night shifts in patients with SWD. This non-confirmatory study included two treatment arms: LML134 and placebo. After a screening period, the treatment phase of the study consisted of two overnight stays in a sleep lab in each of two treatment periods, with a minimum one week wash-out in between.

Condition or Disease	Intervention/Treatment	Phase
Circadian Rhythm Disorders	Drug: LML134; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Subject and Investigator-blinded, Placebo Controlled, Cross-over, Multi-center Proof of Concept (PoC) Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and PK of LML134 in Shift Work Disorder (SWD) Patients
• Actual Study Start Date: Jul 26, 2017
• Actual Primary Completion Date: Aug 30, 2018
• Actual Study Completion Date: Sep 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 LML134, then placebo	Drug: LML134; LML134; Drug: Placebo; placebo
Experimental: Group 2 Placebo, then LML134	Drug: LML134; LML134; Drug: Placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Mean Sleep Latency Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT) [Day 1 and Day 2 of each treatment period (midnight until 8:00)]

   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.

Secondary Outcome Measures

1. Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT) [Day 1 and Day 2 of each treatment period (midnight until 8:00)]

   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.

2. Plasma PK Concentration [0 to 34.5 hours post first treatment.]

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

3. Total Time in Bed Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

   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.

4. Sleep Time Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

   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.

5. Sleep Efficiency Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

   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.

6. Wake Time After Persistent Sleep Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

   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.

7. Latency to Onset of Persistent Sleep Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

   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.

8. Number of Awakenings Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

   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.

9. Latency to Rapid Eye Movement (REM) Sleep Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

   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.

10. Number of Sleep Cycles Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

    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).

11. Time Spent in Each Sleep Stage Measured by Polysomnography (PSG) [Day 2 (10:00 until 18:00) of each treatment period]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and female subjects 18 to 65 years of age included.

• Confirmed diagnosis of SWD according to ICSD-3 criteria at Screening.

• Subjects who are at least moderately ill with respect to sleepiness on work nights, including commute to and from work, as assessed by the Clinical Global Impression-Severity scale (CGI-S, score ≥4) at Screening.

• Subjects must work 5 or more night shifts per month, and 2 or more shifts must occur on consecutive nights, with 6 or more hours worked between 10 pm and 8 am, as confirmed by subject at Screening.

• Subjects must have mean sleep latency ≤8 minutes on nighttime MSLT at Screening.

• Subjects must weigh at least 50 kg at Screening to participate in the study, and must have a body mass index (BMI) within the range of 18 - 35 kg/m2. BMI = Body weight (kg) / [Height (m)]2

Exclusion Criteria:

• Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) unless they are using highly effective methods of contraception from start of taking the study medication in the first period until stopping the medication in the second treatment period and for 3 additional days after AND an additional barrier method of contraception will be used while taking the study medication and for 3 additional days in both treatment periods.

• Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 3 days after stopping investigational drug. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of the investigational drug via seminal fluid to their partner.

• Heavy smokers who smoke more than 10 cigarettes a day and occasional or light smokers (not more than 10 cigarettes per day) who are not willing to, or in their own or the investigators opinion are not able to refrain from tobacco/nicotine use for at least 12 hours without nicotine craving or other withdrawal symptoms

• Subjects for whom it is not safe to discontinue or who are unwilling to discontinue use of modafinil, hypnotics, and antihistamines for the periods specified in the prohibited medication section.

• Heavy caffeine consumers, i.e. subjects who consume greater than 850 mg of caffeine per day (approximate equivalent of three tall cups of Starbucks coffee) in coffee, tea, or other caffeine-containing drinks.

• Subjects who have high risk of obstructive sleep apnea, indicated by score of 5 or more on the STOP-BANG questionnaire.

• Presence of any sleep disorder other than SWD, as confirmed by PSG at screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Los Angeles	California	United States	92868
2	Novartis Investigative Site	San Diego	California	United States	92103
3	Novartis Investigative Site	Miami	Florida	United States	33173
4	Novartis Investigative Site	Oakland Park	Florida	United States	33334
5	Novartis Investigative Site	Atlanta	Georgia	United States	30342
6	Novartis Investigative Site	Chevy Chase	Maryland	United States	20815
7	Novartis Investigative Site	New York	New York	United States	10019
8	Novartis Investigative Site	Cincinnati	Ohio	United States	45255

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 9, 2018
• Statistical Analysis Plan - Dec 12, 2018

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03141086
• Other Study ID Numbers: CLML134X2201
• First Posted: May 4, 2017
• Last Update Posted: Jan 5, 2021
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: shift work disorder
• Additional relevant MeSH terms: Chronobiology Disorders; Disease

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Group 1: LML134, Then Placebo	Group 2: Placebo, Then LML134
Arm/Group Description	LML134, then placebo	Placebo, then LML134
Period Title: Overall Study
STARTED	7	17
COMPLETED	6	12
NOT COMPLETED	1	5

Baseline Characteristics

Arm/Group Title	Group 1: LML134, Then Placebo	Group 2: Placebo, Then LML134	Total
Arm/Group Description	LML134, then placebo	Placebo, then LML134	Total of all reporting groups
Overall Participants	7	17	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.0 (10.42)	39.3 (10.00)	40.7 (10.13)
Sex: Female, Male (Count of Participants)
Female	1 14.3%	3 17.6%	4 16.7%
Male	6 85.7%	14 82.4%	20 83.3%
Race/Ethnicity, Customized (Count of Participants)
Black Or African American	6 85.7%	6 35.3%	12 50%
White	1 14.3%	11 64.7%	12 50%

Outcome Measures

1. Primary Outcome

Title	Mean Sleep Latency Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
Description	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.
Time Frame	Day 1 and Day 2 of each treatment period (midnight until 8:00)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	20	23
Mean (Standard Deviation) [min]	6.76 (4.154)	4.12 (2.993)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LML134 5mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1272
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.711
	Confidence Interval	(2-Sided) 95%; -1.340 to 4.762
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
Description	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.
Time Frame	Day 1 and Day 2 of each treatment period (midnight until 8:00)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	20	23
01:30 (3.5 hours post dose)	8.73 (6.191)	5.27 (5.065)
03:30 (5.5 hours post dose)	7.13 (5.188)	4.57 (4.494)
05:30 (7.5 hours post dose)	5.18 (5.160)	3.38 (3.398)
07:30 (9.5 hours post dose)	5.29 (4.772)	3.25 (2.726)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LML134 5mg, Placebo
	Comments	3.5 hours post dose
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0607
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.866
	Confidence Interval	(2-Sided) 95%; -0.821 to 6.553
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LML134 5mg, Placebo
	Comments	5.5 hours post dose
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0919
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.975
	Confidence Interval	(2-Sided) 95%; -1.024 to 4.973
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LML134 5mg, Placebo
	Comments	7.5 hours post dose
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0811
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.576
	Confidence Interval	(2-Sided) 95%; -0.697 to 3.848
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LML134 5mg, Placebo
	Comments	9.5 hours post dose
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2026
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.879
	Confidence Interval	(2-Sided) 95%; -1.268 to 3.026
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Plasma PK Concentration
Description	Plasma PK concentration. Due to sparse sampling, only plasma concentrations were calculated and no PK parameter was evaluated by non-compartmental analysis.
Time Frame	0 to 34.5 hours post first treatment.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LML134 5mg
Arm/Group Description	LML134 5mg
Measure Participants	21
pre-dose	0 (0)
0.25 hours post dose	0.184 (0.406)
3 hours post dose	24.1 (11.3)
12 hours post dose	6.53 (5.25)
24 hours post dose	1.31 (1.59)
34.5 hrs post 1st dose (10.5 hrs post 2nd dose)	7.55 (5.72)

4. Secondary Outcome

Title	Total Time in Bed Measured by Polysomnography (PSG)
Description	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.
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	19	23
Mean (Standard Deviation) [min]	479.9 (0.16)	480.0 (0.14)

5. Secondary Outcome

Title	Sleep Time Measured by Polysomnography (PSG)
Description	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.
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	19	23
Mean (Standard Deviation) [min]	253.8 (102.53)	294.8 (87.94)

6. Secondary Outcome

Title	Sleep Efficiency Measured by Polysomnography (PSG)
Description	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.
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	19	23
Mean (Standard Deviation) [percentage of time]	53.1 (21.17)	61.4 (18.32)

7. Secondary Outcome

Title	Wake Time After Persistent Sleep Measured by Polysomnography (PSG)
Description	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.
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	19	23
Mean (Standard Deviation) [min]	214.9 (101.88)	174.2 (87.48)

8. Secondary Outcome

Title	Latency to Onset of Persistent Sleep Measured by Polysomnography (PSG)
Description	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.
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	19	23
Mean (Standard Deviation) [min]	8.1 (8.92)	11.0 (12.63)

9. Secondary Outcome

Title	Number of Awakenings Measured by Polysomnography (PSG)
Description	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.
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	19	23
Mean (Standard Deviation) [awakenings]	11.7 (5.29)	12.2 (7.45)

10. Secondary Outcome

Title	Latency to Rapid Eye Movement (REM) Sleep Measured by Polysomnography (PSG)
Description	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.
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	19	23
Mean (Standard Deviation) [min]	89.7 (53.09)	44.9 (38.05)

11. Secondary Outcome

Title	Number of Sleep Cycles Measured by Polysomnography (PSG)
Description	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).
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	0	0

12. Secondary Outcome

Title	Time Spent in Each Sleep Stage Measured by Polysomnography (PSG)
Description	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.
Time Frame	Day 2 (10:00 until 18:00) of each treatment period

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LML134 5mg	Placebo
Arm/Group Description	LML134 5mg	Placebo
Measure Participants	19	23
N1	21.6 (13.95)	25.1 (16.37)
N2	145.7 (55.68)	155.2 (58.84)
N3	43.6 (32.70)	51.1 (29.99)
REM	42.9 (30.21)	63.3 (26.52)

Adverse Events

Time Frame	Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
Arm/Group Title	LML134 5mg		Placebo
Arm/Group Description	LML134 5mg		Placebo
All Cause Mortality
	LML134 5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/23 (0%)
Serious Adverse Events
	LML134 5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	LML134 5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/21 (23.8%)		3/23 (13%)
Gastrointestinal disorders
Nausea	1/21 (4.8%)		0/23 (0%)
Vomiting	1/21 (4.8%)		0/23 (0%)
Infections and infestations
Viral infection	1/21 (4.8%)		0/23 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/21 (4.8%)		0/23 (0%)
Nervous system disorders
Headache	3/21 (14.3%)		3/23 (13%)
Psychiatric disorders
Anxiety	1/21 (4.8%)		0/23 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/21 (0%)		1/23 (4.3%)
Oropharyngeal pain	1/21 (4.8%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.