Clinical trial NCT03141086: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Circadian Rhythm Disorders
Keywords: shift work disorder
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-05-04
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Mean Sleep Latency Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
timeFrame: Day 1 and Day 2 of each treatment period (midnight until 8:00)
Secondary outcomes:
measure: Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
timeFrame: Day 1 and Day 2 of each treatment period (midnight until 8:00)
measure: Plasma PK Concentration
timeFrame: 0 to 34.5 hours post first treatment.
measure: Total Time in Bed Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
measure: Sleep Time Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
measure: Sleep Efficiency Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
measure: Wake Time After Persistent Sleep Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
measure: Latency to Onset of Persistent Sleep Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
measure: Number of Awakenings Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
measure: Latency to Rapid Eye Movement (REM) Sleep Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
measure: Number of Sleep Cycles Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
measure: Time Spent in Each Sleep Stage Measured by Polysomnography (PSG)
timeFrame: Day 2 (10:00 until 18:00) of each treatment period
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Oakland Park
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Chevy Chase
country: United States
facility: Novartis Investigative Site
state: Maryland
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
Study officials:
References: