Circadian Rhythm DisordersPhase 2NCT03141086
A Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder
A Phase 2 study testing LML134 in people with Circadian Rhythm Disorders, run by Novartis Pharmaceuticals at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Circadian Rhythm Disorders
- What is being tested?
- LML134
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 8 sitesUnited States
- Study dates
- 26 Jul 2017to 12 Sep 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Novartis Investigative Site
Atlanta, Georgia, 30342
Novartis Investigative Site
Chevy Chase, Maryland, 20815
Novartis Investigative Site
Cincinnati, Ohio, 45255
Novartis Investigative Site
Los Angeles, California, 92868
Novartis Investigative Site
Miami, Florida, 33173
Novartis Investigative Site
New York, New York, 10019
Novartis Investigative Site
Oakland Park, Florida, 33334
Novartis Investigative Site
San Diego, California, 92103
About this study
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
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.
- Conditions
- Circadian Rhythm Disorders
- Being tested
- LML134, Placebo
- Keywords
- shift work disorder
- Medical subject headings
- Chronobiology Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LML134Drug
LML134
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | LML134, then placebo Receives: Drug: LML134; Drug: Placebo |
| Group 2 | Experimental | Placebo, then LML134 Receives: Drug: LML134; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 and Day 2 of each treatment period (midnight until 8:00)
Secondary outcomes (11)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Day 2 (10:00 until 18:00) of each treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2017
- Study start26 Jul 2017
- Primary completion30 Aug 2018
- Study completion12 Sep 2018
Why it stopped: CLML134X2201 was terminated due to business reasons and not to safety findings
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Circadian Rhythm DisordersStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03141086
- Sponsor's protocol ID
- CLML134X2201
- Status last verified
- Jun 2020
- First submitted
- 28 Apr 2017
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03141086
- Acronym / sponsor ID
- CLML134X2201
- Conditions
- Circadian Rhythm Disorders
- Keywords
- shift work disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: CLML134X2201 was terminated due to business reasons and not to safety findings
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Jul 2017 (actual)
- Primary completion
- 30 Aug 2018 (actual)
- Study completion
- 12 Sep 2018 (actual)
- First posted
- 4 May 2017 (actual)
- Results
- Posted 24 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: LML134, Drug: PlaceboLML134, then placebo |
| Group 2 | Experimental | Drug: LML134, Drug: PlaceboPlacebo, then LML134 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LML134LML134 | Drug | Group 1, Group 2 |
| Placeboplacebo | Drug | Group 1, Group 2 |
Primary outcome
Mean Sleep Latency Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
Time frame: 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.
11 secondary outcomes
Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
Time frame: Day 1 and Day 2 of each treatment period (midnight until 8:00)
Plasma PK Concentration
Time frame: 0 to 34.5 hours post first treatment.
Total Time in Bed Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Sleep Time Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Sleep Efficiency Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Wake Time After Persistent Sleep Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Latency to Onset of Persistent Sleep Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Number of Awakenings Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Latency to Rapid Eye Movement (REM) Sleep Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Number of Sleep Cycles Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Time Spent in Each Sleep Stage Measured by Polysomnography (PSG)
Time frame: Day 2 (10:00 until 18:00) of each treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LML134 in people with Circadian Rhythm Disorders, run by Novartis Pharmaceuticals at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Sleep Latency Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT) (time frame: Day 1 and Day 2 of each treatment period (midnight until 8:00)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2021; AzTrials last refreshed its copy on 26 Oct 2026.