NCT00893789终止3 期
A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dosage Study to Evaluate the Efficacy and Safety of Armodafinil (50, 150, and 250 mg/Day) as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 117
- 试验地点
- 73
- 主要终点
- Change From Baseline in Multiple Sleep Latency Test (MSLT) at Endpoint (Last Postbaseline Observation Up to Week 12)
研究概览
简要总结
The primary objective of the study is to determine whether armodafinil treatment is more effective than placebo treatment in patients with excessive sleepiness associated with mild or moderate closed traumatic brain injury (TBI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient had a mild (Glasgow Coma Scale [GCS] score 13-15) or moderate (GCS score 9-12) closed TBI at the time of the injury, and the injury occurred 1 to 10 years prior to screening.
- •The patient had a Glasgow Outcome Scale score of 5 at the screening visit.
- •The patient had an Epworth Sleepiness Scale (ESS) score of at least 10 at screening.
- •The patient had a mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of 4 naps) of less than 8 minutes at baseline.
- •The patient had a Clinical Global Impression of Severity of Illness (CGI-S) rating relating to their excessive sleepiness of 4 or more at the screening and baseline visits.
- •The patient had a complaint of excessive sleepiness (at least 5 days/week on average) for at least 3 months, and the excessive sleepiness began within 12 months of the TBI.
- •Written informed consent was obtained.
- •The patient was a man or woman of any ethnic origin 18 to 65 years of age.
- •If admitted to an inpatient treatment facility, the patient was discharged at least 1 month prior to the screening visit.
- •The patient did not have any medical or psychiatric disorders that could account for the excessive sleepiness.
- •Women of childbearing potential (not surgically sterile or 2 years postmenopausal), used a medically accepted method of contraception, and continued use of one of these methods for the duration of the study (and for 30 days after participation in the study). Acceptable methods of contraception included: abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method, or intrauterine device (IUD).
- •The patient was in otherwise good health, as judged by the investigator, on the basis of a medical and psychiatric history, physical examination, electrocardiogram (ECG), serum chemistry, hematology, and urinalysis.
- •The patient was willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.
- •The patient had a Mini Mental State Examination (MMSE) score of more than 26 at the screening visit.
- •The patient was on stable dosages of medications (allowed by the protocol) for a minimum of 3 months (selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), 8 weeks (contraceptives), or 4 weeks (all other allowed medication) before the screening visit and was not likely to require a change in therapy for at least 12 weeks on the basis of the investigators' assessment.
- •The patient had a habitual bedtime between 2100 and
- •The patient had no other head injuries that, based on medical record documentation or history from the patient and reliable informant (if available), were temporally related to the onset or to any worsening of excessive sleepiness.
- •The patient had no other head injury fulfilling the criteria for TBI within ±1 year of the TBI identified according to criterion (a1).
排除标准
- •The patient had a history of 2 or more episodes of transient loss of consciousness (LOC) without clear medical explanation, or had a history of known or suspected pseudo seizure (psychogenic seizure). Patients with a history of seizure or epilepsy may have been eligible following discussion with the medical monitor.
- •The patient required, or was likely to require, treatment with anticonvulsant medication during the study, or had taken anticonvulsant medication within 6 months before the screening visit.
- •The patient had an unstable or uncontrolled medical (including illnesses related to the cardiovascular [including patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who had experienced the mitral valve prolapse syndrome], renal, or hepatic systems or surgical) condition (treated or untreated) or was not a suitable candidate for treatment with armodafinil, as judged by the investigator.
- •The patient had neurosurgery involving the brain or brainstem.
- •The patient had a history of schizophrenia, bipolar disorder, psychotic depression, or other psychotic episode.
- •The patient had any current Axis I disorder (including depression and posttraumatic stress disorder [PTSD]), as assessed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (SCID). The patient had any Axis II disorder (as assessed by SCID) that, in the opinion of the investigator, would affect patient participation in the study or full compliance with study procedures.
- •The patient had a history of, or currently met The International Classification of Sleep Disorders, Edition 2 (ICSD 2) (American Academy of Sleep Medicine 2005) criteria for narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), shift work sleep disorder (SWSD), or any other sleep disorder associated with excessive daytime sleepiness; or the patient had a history of idiopathic hypersomnia, insomnia (requiring treatment), or sleep disorder before the development of the TBI.
- •The patient had 85% or less sleep efficiency (sleep duration ÷ time in bed x 100%) as determined from nocturnal polysomnography (NPSG).
- •The patient had any disorder that may interfere with drug absorption, distribution, metabolism, or excretion.
- •The patient used any medications, including over-the-counter (OTC) medicines disallowed by the protocol, within 7 days or 5 half lives (medication or its active metabolites), whichever was longer, before the screening visit.
- •The patient had a need for chronic pain medications.
- •In the judgment of the investigator, the patient had a clinically significant deviation from normal in the physical examination.
- •In the judgment of the investigator, the patient had any clinically significant ECG finding.
- •The patient had a diagnosis of any type of dementia.
- •The patient had a history of suicidal ideation (considered by the investigator to be of current clinical significance), or was currently suicidal.
- •The patient had a known hypersensitivity to armodafinil, racemic modafinil, or any component of the study drug tablets. Armodafinil tablets contain the following inactive ingredients: croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, and pregelatinized starch.
- •The patient had a history of any clinically significant cutaneous drug reaction, or a history of clinically significant hypersensitivity reaction, including multiple allergies or drug reactions.
- •The patient had a clinical laboratory test value(s) outside the range(s) specified by protocol (or any other clinically significant laboratory abnormality), and the medical monitor had not provided written approval for study participation.
- •The patient had a history (within the past 5 years) of alcohol, narcotic, or any other drug abuse (with the exception of nicotine) as defined by the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, 4th Edition, Text Revision (DSM-IV-TR), or the patient had current evidence of substance use, without medical explanation, confirmed by results of a urine drug screen (UDS).
- •The patient had taken armodafinil, modafinil or other stimulant medication for excessive sleepiness within 1 month of the screening visit.
- •The patient was a pregnant or lactating woman. (Any women becoming pregnant during the study were to be withdrawn from the study.)
- •The patient was known to have tested positive for human immunodeficiency virus (HIV).
- •The patient consumed an average of more than 600 mg of caffeine per day, including coffee, tea and/or other caffeine-containing beverages or food.
- •The patient used any investigational drug within 1 month before the screening visit.
- •The patient was receiving workmen's compensation or was in active litigation with regard to TBI.
- •The patient had a self-reported Hamilton Depression Rating Scale, 6 Item Version (S HAM D6) score of more than 4 at the screening visit.
研究组 & 干预措施
1
Experimental
Armodafinil 50 mg/day
干预措施: Armodafinil (Drug)
2
Experimental
Armodafinil 150 mg/day
干预措施: Armodafinil (Drug)
3
Experimental
Armodafinil 250 mg/day
干预措施: Armodafinil (Drug)
4
Placebo Comparator
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in Multiple Sleep Latency Test (MSLT) at Endpoint (Last Postbaseline Observation Up to Week 12)
时间窗: Baseline, last postbaseline observation up to Week 12
The MSLT is an objective assessment of sleepiness that measures the likelihood of falling asleep. Four 20-minute (maximum) MSLT naps were performed at 0900, 1100, 1300, and 1500. The participant, dressed in nonconstricting clothes, was instructed to lie quietly and attempt sleep. Each MSLT nap continued until: (a) 3 consecutive 30-second epochs of stage 1 sleep were reached or (b) any single, 30-second epoch of stage 2, 3, 4, or rapid eye movement (REM) sleep was reached. Sleep latency for each nap and average sleep latency for the 4 naps were tabulated. According to clinical protocol for the MSLT, each nap was terminated after 20 minutes if no sleep occurred. If a participant did not fall asleep in 20 minutes, his/her sleep latency for that nap was set to 20 minutes. Sleep latency was measured as the elapsed time from lights-out to the first epoch scored as sleep. With a 30-second scoring epoch, this criterion was reached when sleep occupied at least 16 seconds of any epoch.
Percentage of Responders and Nonresponders According to Clinical Global Impression of Change (CGI-C) Ratings at Endpoint (Last Postbaseline Observation Up to Week 12)
时间窗: Last postbaseline observation up to Week 12
The CGI-C is the clinician's rating of disease severity as compared with pretreatment, assessed by the Clinical Global Impression of Severity (CGI-S). Severity of illness, as related to excessive sleepiness, was assessed at baseline by the CGI-S, which consists of 7 categories: normal-shows no sign of illness, borderline ill, mildly (slightly) ill, moderately ill, markedly ill, severely ill, and among the most extremely ill. The clinician assessed the change from baseline in the participant's condition, as related to excessive sleepiness, in response to treatment. The CGI-C uses the following 7 categories and scoring assignments: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse. Responders were defined as those participants who were considered much or very much improved on the CGI-C. Those in all other categories of the CGI-C were considered nonresponders.
次要结局
- Change From Baseline in Mean Sleep Latency From the MSLT at Weeks 4, 8, and 12(Baseline, Weeks 4, 8, and 12)
- Change From Baseline in Traumatic Brain Injury - Work Instability Scale (TBI-WIS) Total Score At Weeks 4, 8, 12 and Endpoint (Last Postbaseline Observation Up to Week 12)(Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12))
- Plasma Concentrations of Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) at Weeks 4, 8, and 12 (or Last Postbaseline Observation Up to Week 12)(Weeks 4, 8, and 12 (or last postbaseline observation, up to Week 12))
- Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Withdrawals Due to AEs(Screening through Week 12)
- Number of Participants With Notable Blood Pressure Values Per World Health Organization Criteria(Baseline, last postbaseline observation up to Week 12)
- Percentage of Responders and Nonresponders According to Clinical Global Impression of Change (CGI-C) Ratings at Weeks 2, 4, 8, and 12(Weeks 2, 4, 8, and 12)
- Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 12 and Endpoint (Last Postbaseline Observation Up to Week 12)(Baseline, Week 12, Endpoint (last postbaseline observation, up to Week 12))
- Change From Baseline in the Total Score From the Self-Reported Hamilton Depression Rating Scale, 6 Item Version (S-HAM-D6) at Weeks 2, 4, 8, 12 and Endpoint (Last Postbaseline Observation Up to 12 Weeks)(Baseline, Weeks 2, 4, 8, 12, and Endpoint (last postbaseline observation up to 12 weeks))
- Change From Baseline in the Total Sleep Time As Assessed by Nocturnal Polysomnography (NPSG) at Weeks 2, 4, 12 and Endpoint (Last Postbaseline Observation Up to 12 Weeks)(Baseline, Weeks 2, 4, 12, and Endpoint (last postbaseline observation up to 12 weeks))
- Number of Participants With Clinically Significant Abnormal Postbaseline Serum Chemistry Values(Baseline, last postbaseline observation up to Week 12)
- Physical Examination Findings Shifts From Baseline to Endpoint (Last Postbaseline Observation, up to Week 12)(Baseline through Endpoint (last postbaseline observation, up to Week 12))
- Percentage of Participants Answering "No" to All Questions on the Columbia-Suicide Severity Rating Scale Since Last Visit Version (C-SSRS SLV) at Weeks 2, 4, 8, 12 and Endpoint (Last Postbaseline Observation Up to Week 12)(Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12))
- Concomitant Medication Usage In ≥5% of Participants Throughout the Study(Screening through Week 12)
- Number of Participants With Clinically Significant Abnormal Postbaseline Hematology Values(Baseline, last postbaseline observation up to Week 12)
- Number of Participants With Clinically Significant Abnormal Postbaseline Urinalysis Values(Baseline, last postbaseline observation up to Week 12)
- Number of Participants With Clinically Significant Abnormal Vital Sign Values(Baseline, last postbaseline observation up to Week 12)
- Electrocardiogram (ECG) Findings Shifts From Baseline to Overall(Baseline through Endpoint (last postbaseline observation, up to Week 12))
研究者
研究点 (73)
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