A Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder
Condition: Circadian Rhythm Disorders
MeSH terms: Chronobiology Disorders
Intervention: LML134; Placebo
Intervention description: LML134; placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: shift work disorder

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.