Back to resultsA Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder
Primary Purpose
Circadian Rhythm Disorders
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LML134
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Circadian Rhythm Disorders focused on measuring shift work disorder
Eligibility Criteria
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.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group 1
Group 2
Arm Description
LML134, then placebo
Placebo, then LML134
Outcomes
Primary Outcome Measures
Mean Sleep Latency Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
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
Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
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.
Plasma PK Concentration
Plasma PK concentration. Due to sparse sampling, only plasma concentrations were calculated and no PK parameter was evaluated by non-compartmental analysis.
Total Time in Bed Measured by Polysomnography (PSG)
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.
Sleep Time Measured by Polysomnography (PSG)
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.
Sleep Efficiency Measured by Polysomnography (PSG)
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.
Wake Time After Persistent Sleep Measured by Polysomnography (PSG)
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.
Latency to Onset of Persistent Sleep Measured by Polysomnography (PSG)
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.
Number of Awakenings Measured by Polysomnography (PSG)
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.
Latency to Rapid Eye Movement (REM) Sleep Measured by Polysomnography (PSG)
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.
Number of Sleep Cycles Measured by Polysomnography (PSG)
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 Spent in Each Sleep Stage Measured by Polysomnography (PSG)
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.
Full Information
NCT ID
NCT03141086
First Posted
April 28, 2017
Last Updated
December 9, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03141086
Brief Title
A Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
CLML134X2201 was terminated due to business reasons and not to safety findings
Study Start Date
July 26, 2017 (Actual)
Primary Completion Date
August 30, 2018 (Actual)
Study Completion Date
September 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Circadian Rhythm Disorders
Keywords
shift work disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
LML134, then placebo
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Placebo, then LML134
Intervention Type
Drug
Intervention Name(s)
LML134
Intervention Description
LML134
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo
Primary Outcome Measure Information:
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)
Secondary Outcome Measure Information:
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)
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.
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
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
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
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
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
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Novartis Investigative Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Novartis Investigative Site
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Novartis Investigative Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33173
Country
United States
Facility Name
Novartis Investigative Site
City
Oakland Park
State/Province
Florida
ZIP/Postal Code
33334
Country
United States
Facility Name
Novartis Investigative Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Novartis Investigative Site
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Novartis Investigative Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45255
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=406
Description
A Plain Language Trial Summary is available on novartisclinicatrials.com
Learn more about this trial
A Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder
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