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Study to Evaluate the Efficacy and Safety of Armodafinil as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury

Primary Purpose

Traumatic Brain Injury

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Armodafinil

Placebo

About this trial

This is an interventional treatment trial for Traumatic Brain Injury

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 2400.
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).

Exclusion Criteria:

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Armodafinil 50 mg/day

Armodafinil 150 mg/day

Armodafinil 250 mg/day

Placebo

Outcomes

Primary Outcome Measures

Change From Baseline in Multiple Sleep Latency Test (MSLT) at Endpoint (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)

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.

Secondary Outcome Measures

Change From Baseline in Mean Sleep Latency From the MSLT at Weeks 4, 8, and 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. 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 Weeks 2, 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)

The TBI-WIS is a validated participant-rated instrument for assessing a participant's functional ability after TBI and the functional demands of their job. The assessment consists of 36 questions to which the participant responded with a "true" or "not true" answer. To score the questionnaire, the number of "true" responses is counted: if < 2, the risk is low; 2 to 23, the risk is medium; and >23, the risk is high, for work instability. Score range is 0 (lowest risk for work instability) to 36 (highest risk for work instability).

Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 12 and Endpoint (Last Postbaseline Observation Up to Week 12)

The patient's evaluation of excessive daytime sleepiness was measured by the ESS. The ESS score is based on responses to questions referring to 8 everyday situations (eg, sitting and reading, talking to someone, being stopped in traffic) and reflects a patient's propensity to fall asleep in those situations. The ESS score is derived from the sum of the values from questions corresponding to the 8 situations. Scores for the ESS range from 0 to 24, with a higher score indicating a greater daytime sleepiness. This test was self-administered.

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)

The C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors since last visit (SLV). The number of participants answering 'no' to all 9 yes/no questions about suicidal behaviors, ideations, and acts are presented. Questions included the presence of the following: a wish to be dead; nonspecific active suicidal thoughts; actual suicide attempt; non-suicidal self-injurious behavior; interrupted attempt; aborted attempt; suicidal behavior; preparatory suicidal acts or behavior; and completed suicide.

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)

The self-reported S-HAM-D6 is a validated scale developed from the core depressive items of the 17 Item Hamilton Depression Inventory (HAM-D17). The HAM-D6 (Items 1, 2, 7, 8, 10, 13 from the 17-item HAMD) evaluates "core" symptoms of Major Depressive Disorder (MDD). The assessment consists of 6 items representing depressed mood, guilt, work and activities, retardation, psychic anxiety, and general somatic symptoms. Each item is evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). Total scores range from 0 (normal) to 22 (severe). Scores greater than 12 indicate moderate to severe depression and scores less than 12 indicate mild depression.

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)

NPSG continuously records normal and abnormal physiological activity during an entire night. It documents the adequacy of sleep, including the frequency, duration, and total amounts of stage 1-2, stage 3-4 (slow wave sleep), and rapid eye movement (REM) sleep.

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)

To evaluate the impact of treatment with armodafinil on the pharmacokinetics of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) (as appropriate), plasma concentrations at weeks 4, 8, and 12 (or last postbaseline observation) were to be assessed.

Concomitant Medication Usage In ≥5% of Participants Throughout the Study

Therapeutic classification of concomitant medications used by ≥5% of participants throughout the study. Participants are counted only once in each therapeutic class category. Medications were included in the table if the proportion of participants in the combined armodafinil treatment group was ≥5%.

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Withdrawals Due to AEs

AE=any untoward medical occurrence in a patient that develops or worsens in severity during the conduct of the clinical study of a pharmaceutical product and does not necessarily have a causal relationship to the study drug. SAE=any AE that resulted in any of the following: death; a life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly or birth defect; an important medical event that required medical intervention to prevent 1 of the outcomes listed in this definition. Treatment-related AEs=definite, probable, possible, or missing relationship. Protocol-defined AEs=treatment-emergent adverse events associated with skin rash, hypersensitivity reaction, emergent suicidal ideation or suicide attempt, depression, psychosis (including hypomanic or manic episode), and seizure or suspected seizure were considered to be of potential clinical importance.

Number of Participants With Clinically Significant Abnormal Postbaseline Serum Chemistry Values

Normal ranges for serum chemistry values: blood urea nitrogen (BUN), 1.43 - 8.57 mmol/L; uric acid, 124.91 - 493.68 μmol/L; aspartate aminotransferase (AST), 11 - 36 U/L; gamma-glutamyl transpeptidase (GGT), 10 - 61 U/L; total bilirubin, 3.42 - 20.52 μmol/L.

Number of Participants With Clinically Significant Abnormal Postbaseline Hematology Values

Normal ranges for hematology values: white blood cell (WBC) count, 3.8 - 10.7 x 10^9/L; absolute neutrophil count (ANC), 1.96 - 7.23 x 10^9/L. Participants may have had more than one clinically significant abnormal value.

Number of Participants With Clinically Significant Abnormal Postbaseline Urinalysis Values

Participants with at least one clinically significant postbaseline urinalysis abnormality, specifically presented is blood (hemoglobin) in urine >=2 units increase from baseline.

Number of Participants With Clinically Significant Abnormal Vital Sign Values

Criteria for clinically significant abnormal vital signs values: heart rate, ≤50 beats per minute (bpm) and decrease from baseline of ≥15 bpm; sitting systolic blood pressure, ≤90 mm Hg and decrease from baseline of ≥20 mm Hg; sitting diastolic blood pressure, ≤50 mm Hg and decrease from baseline of ≥15 mm Hg.

Number of Participants With Notable Blood Pressure Values Per World Health Organization Criteria

Criteria for World Health Organization (WHO) notable blood pressure (BP) values: systolic blood pressure, ≥140 mm Hg plus increase of ≥10% from baseline; diastolic blood pressure, ≥90 mm Hg plus increase of ≥10% from baseline.

Electrocardiogram (ECG) Findings Shifts From Baseline to Overall

Number of participants with shifts from normal/abnormal 12-lead ECG findings at baseline (BL) to (→) normal/abnormal findings overall are presented. For overall, the worst postbaseline finding (the abnormal finding if there are both normal and abnormal findings) for the participant between baseline and endpoint (defined as last postbaseline observation, up to Week 12) is summarized. Shifts (normal and abnormal) from baseline to overall are summarized using participant counts. Any ECG finding that was judged by the investigator as a clinically meaningful change (worsening) compared to baseline was recorded as an adverse event.

Physical Examination Findings Shifts From Baseline to Endpoint (Last Postbaseline Observation, up to Week 12)

Number of participants with shifts from normal/abnormal physical examination findings at baseline (BL) to (→) normal/abnormal findings at endpoint (EP, defined as last postbaseline observation, up to Week 12). Shifts (normal and abnormal) from baseline to endpoint are summarized using participant counts for each physical examination category. A newly diagnosed finding was defined as being normal or missing at baseline and abnormal at least once during the study. Any physical examination finding that was judged by the investigator as a clinically significant change (worsening) compared to a baseline value was considered an adverse event. HEENT=head, eyes, ears, nose, throat.

Full Information

NCT ID

NCT00893789

First Posted

May 4, 2009

Last Updated

December 8, 2021

Sponsor

Cephalon, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00893789

Brief Title

Study to Evaluate the Efficacy and Safety of Armodafinil as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Terminated

Why Stopped

Study has been stopped by sponsor decision.

Study Start Date

April 30, 2009 (Actual)

Primary Completion Date

January 31, 2011 (Actual)

Study Completion Date

January 31, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cephalon, Inc.

4. Oversight

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Traumatic Brain Injury

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

117 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Armodafinil 50 mg/day

Arm Title

Arm Type

Experimental

Arm Description

Armodafinil 150 mg/day

Arm Title

Arm Type

Experimental

Arm Description

Armodafinil 250 mg/day

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Armodafinil

Intervention Description

Armodafinil 50 mg/day

Intervention Type

Drug

Intervention Name(s)

Armodafinil

Intervention Description

Armodafinil 150 mg/day

Intervention Type

Drug

Intervention Name(s)

Armodafinil

Intervention Description

Armodafinil 250 mg/day

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Change From Baseline in Multiple Sleep Latency Test (MSLT) at Endpoint (Last Postbaseline Observation Up to Week 12)

Description

Time Frame

Baseline, last postbaseline observation up to Week 12

Title

Percentage of Responders and Nonresponders According to Clinical Global Impression of Change (CGI-C) Ratings at Endpoint (Last Postbaseline Observation Up to Week 12)

Description

Time Frame

Last postbaseline observation up to Week 12

Secondary Outcome Measure Information:

Title

Change From Baseline in Mean Sleep Latency From the MSLT at Weeks 4, 8, and 12

Description

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. 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.

Time Frame

Baseline, Weeks 4, 8, and 12

Title

Percentage of Responders and Nonresponders According to Clinical Global Impression of Change (CGI-C) Ratings at Weeks 2, 4, 8, and 12

Description

Time Frame

Weeks 2, 4, 8, and 12

Title

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)

Description

Time Frame

Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12)

Title

Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 12 and Endpoint (Last Postbaseline Observation Up to Week 12)

Description

Time Frame

Baseline, Week 12, Endpoint (last postbaseline observation, up to Week 12)

Title

Description

Time Frame

Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12)

Title

Description

Time Frame

Baseline, Weeks 2, 4, 8, 12, and Endpoint (last postbaseline observation up to 12 weeks)

Title

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)

Description

Time Frame

Baseline, Weeks 2, 4, 12, and Endpoint (last postbaseline observation up to 12 weeks)

Title

Description

Time Frame

Weeks 4, 8, and 12 (or last postbaseline observation, up to Week 12)

Title

Concomitant Medication Usage In ≥5% of Participants Throughout the Study

Description

Time Frame

Screening through Week 12

Title

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Withdrawals Due to AEs

Description

Time Frame

Screening through Week 12

Title

Number of Participants With Clinically Significant Abnormal Postbaseline Serum Chemistry Values

Description

Time Frame

Baseline, last postbaseline observation up to Week 12

Title

Number of Participants With Clinically Significant Abnormal Postbaseline Hematology Values

Description

Time Frame

Baseline, last postbaseline observation up to Week 12

Title

Number of Participants With Clinically Significant Abnormal Postbaseline Urinalysis Values

Description

Participants with at least one clinically significant postbaseline urinalysis abnormality, specifically presented is blood (hemoglobin) in urine >=2 units increase from baseline.

Time Frame

Baseline, last postbaseline observation up to Week 12

Title

Number of Participants With Clinically Significant Abnormal Vital Sign Values

Description

Time Frame

Baseline, last postbaseline observation up to Week 12

Title

Number of Participants With Notable Blood Pressure Values Per World Health Organization Criteria

Description

Time Frame

Baseline, last postbaseline observation up to Week 12

Title

Electrocardiogram (ECG) Findings Shifts From Baseline to Overall

Description

Time Frame

Baseline through Endpoint (last postbaseline observation, up to Week 12)

Title

Physical Examination Findings Shifts From Baseline to Endpoint (Last Postbaseline Observation, up to Week 12)

Description

Time Frame

Baseline through Endpoint (last postbaseline observation, up to Week 12)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 2400. 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). Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sponsor's Medical Expert, MD

Organizational Affiliation

Teva Branded Pharmaceutical Products R&D, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Teva Investigational Site 58

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35213

Country

United States

Facility Name

Teva Investigational Site 62

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85712

Country

United States

Facility Name

Teva Investigational Site 40

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85723

Country

United States

Facility Name

Teva Investigational Site 16

City

Hot Springs

State/Province

Arkansas

ZIP/Postal Code

71913

Country

United States

Facility Name

Teva Investigational Site 5

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

Facility Name

Teva Investigational Site 44

City

Fountain Valley

State/Province

California

ZIP/Postal Code

92708

Country

United States

Facility Name

Teva Investigational Site 49

City

La Palma

State/Province

California

ZIP/Postal Code

90623

Country

United States

Facility Name

Teva Investigational Site 51

City

La Palma

State/Province

California

ZIP/Postal Code

90623

Country

United States

Facility Name

Teva Investigational Site 71

City

Mather

State/Province

California

ZIP/Postal Code

95655

Country

United States

Facility Name

Teva Investigational Site 55

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

Teva Investigational Site 33

City

San Diego

State/Province

California

ZIP/Postal Code

92161

Country

United States

Facility Name

Teva Investigational Site 53

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Teva Investigational Site 69

City

Wallingford

State/Province

Connecticut

ZIP/Postal Code

06492

Country

United States

Facility Name

Teva Investigational Site 52

City

Hallandale Beach

State/Province

Florida

ZIP/Postal Code

33009

Country

United States

Facility Name

Teva Investigational Site 47

City

Miami

State/Province

Florida

ZIP/Postal Code

33173

Country

United States

Facility Name

Teva Investigational Site 1

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Teva Investigational Site 18

City

Pembroke Pines

State/Province

Florida

ZIP/Postal Code

33026

Country

United States

Facility Name

Teva Investigational Site 38

City

Saint Petersburg

State/Province

Florida

ZIP/Postal Code

33707

Country

United States

Facility Name

Teva Investigational Site 10

City

Spring Hill

State/Province

Florida

ZIP/Postal Code

34609

Country

United States

Facility Name

Teva Investigational Site 17

City

Tampa

State/Province

Florida

ZIP/Postal Code

33607

Country

United States

Facility Name

Teva Investigational Site 26

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30321

Country

United States

Facility Name

Teva Investigational Site 12

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

Teva Investigational Site 14

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

Teva Investigational Site 68

City

Gainesville

State/Province

Georgia

ZIP/Postal Code

30501

Country

United States

Facility Name

Teva Investigational Site 67

City

Macon

State/Province

Georgia

ZIP/Postal Code

31201

Country

United States

Facility Name

Teva Investigational Site 29

City

Stockbridge

State/Province

Georgia

ZIP/Postal Code

30281

Country

United States

Facility Name

Teva Investigational Site 15

City

Suwanee

State/Province

Georgia

ZIP/Postal Code

30024

Country

United States

Facility Name

Teva Investigational Site 46

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60675-6714

Country

United States

Facility Name

Teva Investigational Site 54

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60675-6714

Country

United States

Facility Name

Teva Investigational Site 59

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60675-6714

Country

United States

Facility Name

Teva Investigational Site 28

City

Danville

State/Province

Indiana

ZIP/Postal Code

46122

Country

United States

Facility Name

Teva Investigational Site 19

City

Fort Wayne

State/Province

Indiana

ZIP/Postal Code

46805

Country

United States

Facility Name

Teva Investigational Site 2

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46250

Country

United States

Facility Name

Teva Investigational Site 39

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46260

Country

United States

Facility Name

Teva Investigational Site 41

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

Teva Investigational Site 9

City

Shawnee Mission

State/Province

Kansas

ZIP/Postal Code

66201

Country

United States

Facility Name

Teva Investigational Site 48

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40217

Country

United States

Facility Name

Teva Investigational Site 32

City

Chevy Chase

State/Province

Maryland

ZIP/Postal Code

20815-6901

Country

United States

Facility Name

Teva Investigational Site 37

City

Belmont

State/Province

Massachusetts

ZIP/Postal Code

02478

Country

United States

Facility Name

Teva Investigational Site 70

City

Brighton

State/Province

Massachusetts

ZIP/Postal Code

02135

Country

United States

Facility Name

Teva Investigational Site 22

City

Saginaw

State/Province

Michigan

ZIP/Postal Code

48604

Country

United States

Facility Name

Teva Investigational Site 7

City

Hattiesburg

State/Province

Mississippi

ZIP/Postal Code

39402

Country

United States

Facility Name

Teva Investigational Site 42

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63143

Country

United States

Facility Name

Teva Investigational Site 56

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68510

Country

United States

Facility Name

Teva Investigational Site 72

City

New York

State/Province

New York

ZIP/Postal Code

10010

Country

United States

Facility Name

Teva Investigational Site 63

City

New York

State/Province

New York

ZIP/Postal Code

10019

Country

United States

Facility Name

Teva Investigational Site 36

City

West Seneca

State/Province

New York

ZIP/Postal Code

14224

Country

United States

Facility Name

Teva Investigational Site 11

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Teva Investigational Site 45

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

Facility Name

Teva Investigational Site 31

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45227

Country

United States

Facility Name

Teva Investigational Site 34

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45246

Country

United States

Facility Name

Teva Investigational Site 57

City

Middleburg Heights

State/Province

Ohio

ZIP/Postal Code

44130

Country

United States

Facility Name

Teva Investigational Site 30

City

Toledo

State/Province

Ohio

ZIP/Postal Code

43623

Country

United States

Facility Name

Teva Investigational Site 3

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73112

Country

United States

Facility Name

Teva Investigational Site 64

City

Clarks Summit

State/Province

Pennsylvania

ZIP/Postal Code

18411

Country

United States

Facility Name

Teva Investigational Site 13

City

Jefferson Hills

State/Province

Pennsylvania

ZIP/Postal Code

15025

Country

United States

Facility Name

Teva Investigational Site 65

City

Columbia

State/Province

South Carolina

ZIP/Postal Code

29201

Country

United States

Facility Name

Teva Investigational Site 61

City

Germantown

State/Province

Tennessee

ZIP/Postal Code

38139

Country

United States

Facility Name

Teva Investigational Site 60

City

Austin

State/Province

Texas

ZIP/Postal Code

78756

Country

United States

Facility Name

Teva Investigational Site 25

City

Dallas

State/Province

Texas

ZIP/Postal Code

75235

Country

United States

Facility Name

Teva Investigational Site 8

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Teva Investigational Site 20

City

Houston

State/Province

Texas

ZIP/Postal Code

77063

Country

United States

Facility Name

Teva Investigational Site 73

City

Kingwood

State/Province

Texas

ZIP/Postal Code

77339

Country

United States

Facility Name

Teva Investigational Site 23

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Teva Investigational Site 35

City

Midvale

State/Province

Utah

ZIP/Postal Code

84047

Country

United States

Facility Name

Teva Investigational Site 66

City

Midvale

State/Province

Utah

ZIP/Postal Code

84047

Country

United States

Facility Name

Teva Investigational Site 24

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23249

Country

United States

Facility Name

Teva Investigational Site 50

City

West Allis

State/Province

Wisconsin

ZIP/Postal Code

53227

Country

United States

Facility Name

Teva Investigational Site 405

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

Teva Investigational Site 404

City

Munchen

ZIP/Postal Code

80331

Country

Germany

Facility Name

Teva Investigational Site 501

City

Pisa

ZIP/Postal Code

56126

Country

Italy

Facility Name

Teva Investigational Site 704

City

Barcelona

ZIP/Postal Code

08003

Country

Spain

Facility Name

Teva Investigational Site 701

City

Madrid

ZIP/Postal Code

28036

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

25325609

Citation

Menn SJ, Yang R, Lankford A. Armodafinil for the treatment of excessive sleepiness associated with mild or moderate closed traumatic brain injury: a 12-week, randomized, double-blind study followed by a 12-month open-label extension. J Clin Sleep Med. 2014 Nov 15;10(11):1181-91. doi: 10.5664/jcsm.4196.

Results Reference

derived

Learn more about this trial

Study to Evaluate the Efficacy and Safety of Armodafinil as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury

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Study to Evaluate the Efficacy and Safety of Armodafinil as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury

Traumatic Brain Injury

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial