A Study to Assess the Wakefulness Promoting Effect, Safety, Tolerability, and Pharmacokinetics (PK) of LML134 in Shift Work Disorder
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.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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California
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Los Angeles、California、美国、92868
- Novartis Investigative Site
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San Diego、California、美国、92103
- Novartis Investigative Site
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Florida
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Miami、Florida、美国、33173
- Novartis Investigative Site
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Oakland Park、Florida、美国、33334
- Novartis Investigative Site
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Georgia
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Atlanta、Georgia、美国、30342
- Novartis Investigative Site
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Maryland
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Chevy Chase、Maryland、美国、20815
- Novartis Investigative Site
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New York
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New York、New York、美国、10019
- Novartis Investigative Site
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Ohio
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Cincinnati、Ohio、美国、45255
- Novartis Investigative Site
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：交叉作业
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Group 1
LML134, then placebo
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安慰剂
LML134
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实验性的：Group 2
Placebo, then LML134
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安慰剂
LML134
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Mean Sleep Latency Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
大体时间：Day 1 and Day 2 of each treatment period (midnight until 8:00)
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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.
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Day 1 and Day 2 of each treatment period (midnight until 8:00)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Sleep Latency at Separate Naps Over Two Consecutive Test Nights as Measured by the the Multiple Sleep Latency Test (MSLT)
大体时间：Day 1 and Day 2 of each treatment period (midnight until 8:00)
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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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Day 1 and Day 2 of each treatment period (midnight until 8:00)
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Plasma PK Concentration
大体时间：0 to 34.5 hours post first treatment.
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Plasma PK concentration.
Due to sparse sampling, only plasma concentrations were calculated and no PK parameter was evaluated by non-compartmental analysis.
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0 to 34.5 hours post first treatment.
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Total Time in Bed Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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
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Sleep Time Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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
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Sleep Efficiency Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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
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Wake Time After Persistent Sleep Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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
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Latency to Onset of Persistent Sleep Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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.
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Day 2 (10:00 until 18:00) of each treatment period
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Number of Awakenings Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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
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Latency to Rapid Eye Movement (REM) Sleep Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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
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Number of Sleep Cycles Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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
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Time Spent in Each Sleep Stage Measured by Polysomnography (PSG)
大体时间：Day 2 (10:00 until 18:00) of each treatment period
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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
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
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
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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Mila (bMotion Technologies)完全的
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Universidad Autonoma de MadridCentro Universitario La Salle完全的