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CLML134X2201 was terminated due to business reasons and not to safety findings
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | LML134, then placebo |
|
| Group 2 | Experimental | Placebo, then LML134 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LML134 | Drug | LML134 |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 and Day 2 of each treatment period (midnight until 8:00) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Los Angeles | California | 92868 | United States | ||
| Novartis Investigative Site |
Not provided
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicatrials.com | View source |
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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
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1: LML134, Then Placebo | LML134, then placebo |
| FG001 | Group 2: Placebo, Then LML134 | Placebo, then LML134 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 9, 2018 | Sep 3, 2019 |
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| Drug |
placebo |
|
| Day 1 and Day 2 of each treatment period (midnight until 8:00) |
| 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. | 0 to 34.5 hours post first treatment. |
| 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. | Day 2 (10:00 until 18:00) of each treatment period |
| 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. | Day 2 (10:00 until 18:00) of each treatment period |
| 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. | Day 2 (10:00 until 18:00) of each treatment period |
| 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. | Day 2 (10:00 until 18:00) of each treatment period |
| 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. | Day 2 (10:00 until 18:00) of each treatment period |
| 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. | Day 2 (10:00 until 18:00) of each treatment period |
| 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. | Day 2 (10:00 until 18:00) of each treatment period |
| 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). | Day 2 (10:00 until 18:00) of each treatment period |
| 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. | Day 2 (10:00 until 18:00) of each treatment period |
| San Diego |
| California |
| 92103 |
| United States |
| Novartis Investigative Site | Miami | Florida | 33173 | United States |
| Novartis Investigative Site | Oakland Park | Florida | 33334 | United States |
| Novartis Investigative Site | Atlanta | Georgia | 30342 | United States |
| Novartis Investigative Site | Chevy Chase | Maryland | 20815 | United States |
| Novartis Investigative Site | New York | New York | 10019 | United States |
| Novartis Investigative Site | Cincinnati | Ohio | 45255 | United States |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1: LML134, Then Placebo | LML134, then placebo |
| BG001 | Group 2: Placebo, Then LML134 | Placebo, then LML134 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Full Analysis Set | Posted | Mean | Standard Deviation | min | Day 1 and Day 2 of each treatment period (midnight until 8:00) |
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| Secondary | 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. | Full analysis set | Posted | Mean | Standard Deviation | min | Day 1 and Day 2 of each treatment period (midnight until 8:00) |
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| Secondary | 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. | Pharmacokinetic analysis set (only analyzed for LML134 treatment period - not analyzed for Placebo period) | Posted | Mean | Standard Deviation | ng/mL | 0 to 34.5 hours post first treatment. |
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| Secondary | 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. | Safety Analysis Set | Posted | Mean | Standard Deviation | min | Day 2 (10:00 until 18:00) of each treatment period |
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| Secondary | 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. | Safety Analysis Set | Posted | Mean | Standard Deviation | min | Day 2 (10:00 until 18:00) of each treatment period |
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| Secondary | 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. | Safety Analysis Set | Posted | Mean | Standard Deviation | percentage of time | Day 2 (10:00 until 18:00) of each treatment period |
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| Secondary | 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. | Safety Analysis Set | Posted | Mean | Standard Deviation | min | Day 2 (10:00 until 18:00) of each treatment period |
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| Secondary | 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. | Safety Analysis Set | Posted | Mean | Standard Deviation | min | Day 2 (10:00 until 18:00) of each treatment period |
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| Secondary | 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. | Safety Analysis Set | Posted | Mean | Standard Deviation | awakenings | Day 2 (10:00 until 18:00) of each treatment period |
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| Secondary | 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. | Safety Analysis Set | Posted | Mean | Standard Deviation | min | Day 2 (10:00 until 18:00) of each treatment period |
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| Secondary | 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). | Safety Analysis set - this outcome measure was not recorded in the Polysomnography testing | Posted | Day 2 (10:00 until 18:00) of each treatment period |
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| Secondary | 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. | Safety Analysis Set | Posted | Mean | Standard Deviation | min | Day 2 (10:00 until 18:00) of each treatment period |
|
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Adverse events were collected for up to 24 days from first dose of study treatment in each treatment period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LML134 5mg | LML134 5mg | 0 | 21 | 0 | 21 | 5 | 21 |
| EG001 | Placebo | Placebo | 0 | 23 | 0 | 23 | 3 | 23 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA (21.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 12, 2018 | Sep 3, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D021081 | Chronobiology Disorders |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
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| Male |
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| White |
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| Title | Denominators | Categories | ||||
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| 0.25 hours post dose |
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| 24 hours post dose |
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| 34.5 hrs post 1st dose (10.5 hrs post 2nd dose) |
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