A Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder

NCT03141086 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CLML134X2201
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

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.

Conditions

Circadian Rhythm Disorders

Keywords

shift work disorder

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (11)

• Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)

  Day 1 and Day 2 of each treatment period (midnight until 8:00)

• Plasma PK Concentration

  0 to 34.5 hours post first treatment.

• Total Time in Bed Measured by Polysomnography (PSG)

  Day 2 (10:00 until 18:00) of each treatment period

• Sleep Time Measured by Polysomnography (PSG)

  Day 2 (10:00 until 18:00) of each treatment period

• Sleep Efficiency Measured by Polysomnography (PSG)

  Day 2 (10:00 until 18:00) of each treatment period

Study Arms (2)

Group 1

EXPERIMENTAL

LML134, then placebo

Drug: LML134; Drug: Placebo

Group 2

EXPERIMENTAL

Placebo, then LML134

Drug: LML134; Drug: Placebo

Interventions

LML134 DRUG

LML134

Group 1; Group 2

Placebo DRUG

placebo

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Novartis Investigative Site

Los Angeles, California, 92868, United States

Location

Novartis Investigative Site

San Diego, California, 92103, United States

Location

Novartis Investigative Site

Miami, Florida, 33173, United States

Location

Novartis Investigative Site

Oakland Park, Florida, 33334, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30342, United States

Location

Novartis Investigative Site

Chevy Chase, Maryland, 20815, United States

Location

Novartis Investigative Site

New York, New York, 10019, United States

Location

Novartis Investigative Site

Cincinnati, Ohio, 45255, United States

Location

Related Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

MeSH Terms

Conditions

Chronobiology Disorders

Condition Hierarchy (Ancestors)

Nervous System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 4, 2017
• Study Start: July 26, 2017
• Primary Completion: August 30, 2018
• Study Completion: September 12, 2018
• Last Updated: January 5, 2021
• Results First Posted: September 24, 2019

Record last verified: 2020-06

Locations

US (8)