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
Study Details
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Armodafinil 50 mg/day |
Drug: Armodafinil
Armodafinil 50 mg/day
|
| Experimental: 2 Armodafinil 150 mg/day |
Drug: Armodafinil
Armodafinil 150 mg/day
|
| Experimental: 3 Armodafinil 250 mg/day |
Drug: Armodafinil
Armodafinil 250 mg/day
|
| Placebo Comparator: 4 Placebo |
Other: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Multiple Sleep Latency Test (MSLT) at Endpoint (Last Postbaseline Observation Up to Week 12) [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) [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 [Baseline, 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 [Weeks 2, 4, 8, and 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.
- 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)]
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) [Baseline, Week 12, 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) [Weeks 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) [Baseline, 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) [Baseline, 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) [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 [Screening through Week 12]
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 [Screening through Week 12]
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 [Baseline, last postbaseline observation up to Week 12]
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 [Baseline, last postbaseline observation up to Week 12]
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 [Baseline, last postbaseline observation up to Week 12]
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 [Baseline, last postbaseline observation up to Week 12]
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 [Baseline, last postbaseline observation up to Week 12]
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 [Baseline through Endpoint (last postbaseline observation, up to Week 12)]
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) [Baseline through 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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Teva Investigational Site 58 | Birmingham | Alabama | United States | 35213 |
| 2 | Teva Investigational Site 62 | Tucson | Arizona | United States | 85712 |
| 3 | Teva Investigational Site 40 | Tucson | Arizona | United States | 85723 |
| 4 | Teva Investigational Site 16 | Hot Springs | Arkansas | United States | 71913 |
| 5 | Teva Investigational Site 5 | Little Rock | Arkansas | United States | 72205 |
| 6 | Teva Investigational Site 44 | Fountain Valley | California | United States | 92708 |
| 7 | Teva Investigational Site 49 | La Palma | California | United States | 90623 |
| 8 | Teva Investigational Site 51 | La Palma | California | United States | 90623 |
| 9 | Teva Investigational Site 71 | Mather | California | United States | 95655 |
| 10 | Teva Investigational Site 55 | San Diego | California | United States | 92103 |
| 11 | Teva Investigational Site 33 | San Diego | California | United States | 92161 |
| 12 | Teva Investigational Site 53 | Santa Monica | California | United States | 90404 |
| 13 | Teva Investigational Site 69 | Wallingford | Connecticut | United States | 06492 |
| 14 | Teva Investigational Site 52 | Hallandale Beach | Florida | United States | 33009 |
| 15 | Teva Investigational Site 47 | Miami | Florida | United States | 33173 |
| 16 | Teva Investigational Site 1 | Orlando | Florida | United States | 32806 |
| 17 | Teva Investigational Site 18 | Pembroke Pines | Florida | United States | 33026 |
| 18 | Teva Investigational Site 38 | Saint Petersburg | Florida | United States | 33707 |
| 19 | Teva Investigational Site 10 | Spring Hill | Florida | United States | 34609 |
| 20 | Teva Investigational Site 17 | Tampa | Florida | United States | 33607 |
| 21 | Teva Investigational Site 26 | Atlanta | Georgia | United States | 30321 |
| 22 | Teva Investigational Site 12 | Atlanta | Georgia | United States | 30342 |
| 23 | Teva Investigational Site 14 | Atlanta | Georgia | United States | 30342 |
| 24 | Teva Investigational Site 68 | Gainesville | Georgia | United States | 30501 |
| 25 | Teva Investigational Site 67 | Macon | Georgia | United States | 31201 |
| 26 | Teva Investigational Site 29 | Stockbridge | Georgia | United States | 30281 |
| 27 | Teva Investigational Site 15 | Suwanee | Georgia | United States | 30024 |
| 28 | Teva Investigational Site 46 | Chicago | Illinois | United States | 60675-6714 |
| 29 | Teva Investigational Site 54 | Chicago | Illinois | United States | 60675-6714 |
| 30 | Teva Investigational Site 59 | Chicago | Illinois | United States | 60675-6714 |
| 31 | Teva Investigational Site 28 | Danville | Indiana | United States | 46122 |
| 32 | Teva Investigational Site 19 | Fort Wayne | Indiana | United States | 46805 |
| 33 | Teva Investigational Site 2 | Indianapolis | Indiana | United States | 46250 |
| 34 | Teva Investigational Site 39 | Indianapolis | Indiana | United States | 46260 |
| 35 | Teva Investigational Site 41 | Iowa City | Iowa | United States | 52242 |
| 36 | Teva Investigational Site 9 | Shawnee Mission | Kansas | United States | 66201 |
| 37 | Teva Investigational Site 48 | Louisville | Kentucky | United States | 40217 |
| 38 | Teva Investigational Site 32 | Chevy Chase | Maryland | United States | 20815-6901 |
| 39 | Teva Investigational Site 37 | Belmont | Massachusetts | United States | 02478 |
| 40 | Teva Investigational Site 70 | Brighton | Massachusetts | United States | 02135 |
| 41 | Teva Investigational Site 22 | Saginaw | Michigan | United States | 48604 |
| 42 | Teva Investigational Site 7 | Hattiesburg | Mississippi | United States | 39402 |
| 43 | Teva Investigational Site 42 | Saint Louis | Missouri | United States | 63143 |
| 44 | Teva Investigational Site 56 | Lincoln | Nebraska | United States | 68510 |
| 45 | Teva Investigational Site 72 | New York | New York | United States | 10010 |
| 46 | Teva Investigational Site 63 | New York | New York | United States | 10019 |
| 47 | Teva Investigational Site 36 | West Seneca | New York | United States | 14224 |
| 48 | Teva Investigational Site 11 | Durham | North Carolina | United States | 27710 |
| 49 | Teva Investigational Site 45 | Winston-Salem | North Carolina | United States | 27157 |
| 50 | Teva Investigational Site 31 | Cincinnati | Ohio | United States | 45227 |
| 51 | Teva Investigational Site 34 | Cincinnati | Ohio | United States | 45246 |
| 52 | Teva Investigational Site 57 | Middleburg Heights | Ohio | United States | 44130 |
| 53 | Teva Investigational Site 30 | Toledo | Ohio | United States | 43623 |
| 54 | Teva Investigational Site 3 | Oklahoma City | Oklahoma | United States | 73112 |
| 55 | Teva Investigational Site 64 | Clarks Summit | Pennsylvania | United States | 18411 |
| 56 | Teva Investigational Site 13 | Jefferson Hills | Pennsylvania | United States | 15025 |
| 57 | Teva Investigational Site 65 | Columbia | South Carolina | United States | 29201 |
| 58 | Teva Investigational Site 61 | Germantown | Tennessee | United States | 38139 |
| 59 | Teva Investigational Site 60 | Austin | Texas | United States | 78756 |
| 60 | Teva Investigational Site 25 | Dallas | Texas | United States | 75235 |
| 61 | Teva Investigational Site 8 | Houston | Texas | United States | 77030 |
| 62 | Teva Investigational Site 20 | Houston | Texas | United States | 77063 |
| 63 | Teva Investigational Site 73 | Kingwood | Texas | United States | 77339 |
| 64 | Teva Investigational Site 23 | San Antonio | Texas | United States | 78229 |
| 65 | Teva Investigational Site 35 | Midvale | Utah | United States | 84047 |
| 66 | Teva Investigational Site 66 | Midvale | Utah | United States | 84047 |
| 67 | Teva Investigational Site 24 | Richmond | Virginia | United States | 23249 |
| 68 | Teva Investigational Site 50 | West Allis | Wisconsin | United States | 53227 |
| 69 | Teva Investigational Site 405 | Berlin | Germany | 10117 | |
| 70 | Teva Investigational Site 404 | Munchen | Germany | 80331 | |
| 71 | Teva Investigational Site 501 | Pisa | Italy | 56126 | |
| 72 | Teva Investigational Site 704 | Barcelona | Spain | 08003 | |
| 73 | Teva Investigational Site 701 | Madrid | Spain | 28036 |
Sponsors and Collaborators
- Cephalon, Inc.
Investigators
- Study Director: Sponsor's Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- C10953/3067/ES/MN
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Period Title: Overall Study | ||||
| STARTED | 29 | 30 | 29 | 29 |
| Safety Analysis Set (SAS) | 29 | 30 | 29 | 29 |
| Full Analysis Set (FAS) | 29 | 29 | 28 | 27 |
| COMPLETED | 23 | 26 | 22 | 16 |
| NOT COMPLETED | 6 | 4 | 7 | 13 |
Baseline Characteristics
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) | Total of all reporting groups |
| Overall Participants | 29 | 30 | 29 | 29 | 117 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
30.2
(11.02)
|
33.2
(9.31)
|
32.3
(10.81)
|
29.4
(11.07)
|
31.3
(10.54)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
14
48.3%
|
13
43.3%
|
13
44.8%
|
13
44.8%
|
53
45.3%
|
| Male |
15
51.7%
|
17
56.7%
|
16
55.2%
|
16
55.2%
|
64
54.7%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
1
3.4%
|
0
0%
|
1
0.9%
|
| Asian |
1
3.4%
|
0
0%
|
0
0%
|
1
3.4%
|
2
1.7%
|
| Black or African American |
2
6.9%
|
2
6.7%
|
6
20.7%
|
4
13.8%
|
14
12%
|
| White |
26
89.7%
|
27
90%
|
22
75.9%
|
24
82.8%
|
99
84.6%
|
| More than one race |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
1
0.9%
|
Outcome Measures
| Title | Change From Baseline in Multiple Sleep Latency Test (MSLT) at Endpoint (Last Postbaseline Observation Up to Week 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. 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. |
| Time Frame | Baseline, last postbaseline observation up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment); n=number of participants with measurements at given time point. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 29 | 28 | 27 |
| Baseline (BL; n=29, 29, 28, 27) |
3.3
(1.79)
|
4.2
(1.69)
|
4.2
(2.05)
|
3.7
(2.04)
|
| Change from BL at Endpoint (n=27, 29, 26, 21) |
2.4
(4.03)
|
2.6
(4.35)
|
5.0
(4.95)
|
7.2
(6.35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Armodafinil 50 mg/Day |
|---|---|---|
| Comments | P-value for "Change from Baseline at Endpoint." | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8336 |
| Comments | The analyses performed were not done in accordance to the study protocol as the study was terminated early and therefore the analyses done were underpowered, no adjustments for multiple comparisons (or step-down analysis rules) were applied. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Armodafinil 150 mg/Day |
|---|---|---|
| Comments | P-value for "Change from Baseline at Endpoint." | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0514 |
| Comments | The analyses performed were not done in accordance to the study protocol as the study was terminated early and therefore the analyses done were underpowered, no adjustments for multiple comparisons (or step-down analysis rules) were applied. | |
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Armodafinil 250 mg/Day |
|---|---|---|
| Comments | P-value for "Change from Baseline at Endpoint." | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | The analyses performed were not done in accordance to the study protocol as the study was terminated early and therefore the analyses done were underpowered, no adjustments for multiple comparisons (or step-down analysis rules) were applied. | |
| Method | ANCOVA | |
| Comments | ||
| 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 | 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. |
| Time Frame | Last postbaseline observation up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment). |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 29 | 28 | 27 |
| Responders |
38
131%
|
41
136.7%
|
54
186.2%
|
48
165.5%
|
| Nonresponders |
62
213.8%
|
59
196.7%
|
46
158.6%
|
52
179.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Armodafinil 50 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7884 |
| Comments | ||
| Method | Pearson's chi-squared | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Armodafinil 150 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2359 |
| Comments | ||
| Method | Pearson's chi-squared | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Armodafinil 250 mg/Day |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4401 |
| Comments | ||
| Method | Pearson's chi-squared | |
| Comments | ||
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment); n=number of participants with data at given time points. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 29 | 28 | 27 |
| Baseline (BL; n=29, 29, 28, 27) |
3.3
(1.79)
|
4.2
(1.69)
|
4.2
(2.05)
|
3.7
(2.04)
|
| Change from BL at Week 4 (n=26, 29, 26, 20) |
3.2
(4.93)
|
2.7
(5.21)
|
4.0
(5.43)
|
7.0
(4.80)
|
| Change from BL at Week 8 (n=24, 27, 24, 17) |
2.1
(4.73)
|
2.5
(4.88)
|
4.2
(5.94)
|
4.2
(5.47)
|
| Change from BL at Week 12 (n=22, 26, 22, 15) |
1.8
(3.87)
|
2.7
(4.53)
|
4.6
(4.39)
|
7.4
(6.38)
|
| Title | Percentage of Responders and Nonresponders According to Clinical Global Impression of Change (CGI-C) Ratings at Weeks 2, 4, 8, and 12 |
|---|---|
| Description | 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. |
| Time Frame | Weeks 2, 4, 8, and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment); n=number of participants with a nonmissing value at given time point. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 29 | 28 | 27 |
| Week 2 Responders (n=28, 29, 27, 23) |
14
48.3%
|
21
70%
|
37
127.6%
|
39
134.5%
|
| Week 2 Nonresponders (n=28, 29, 27, 23) |
86
296.6%
|
79
263.3%
|
63
217.2%
|
61
210.3%
|
| Week 4 Responders (n=27, 29, 26, 20) |
22
75.9%
|
24
80%
|
50
172.4%
|
50
172.4%
|
| Week 4 Nonresponders (n=27, 29, 26, 20) |
78
269%
|
76
253.3%
|
50
172.4%
|
50
172.4%
|
| Week 8 Responders (n=23, 27, 24, 18) |
35
120.7%
|
48
160%
|
54
186.2%
|
56
193.1%
|
| Week 8 Nonresponders (n=23, 27, 24, 18) |
65
224.1%
|
52
173.3%
|
46
158.6%
|
44
151.7%
|
| Week 12 Responders (n=23, 26, 22, 16) |
35
120.7%
|
42
140%
|
55
189.7%
|
56
193.1%
|
| Week 12 Nonresponders (n=23, 26, 22, 16) |
65
224.1%
|
58
193.3%
|
45
155.2%
|
44
151.7%
|
| 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 | 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). |
| Time Frame | Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set (participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment) with a baseline TBI-WIS measurement; n=number of participants with values at given time points. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 24 | 24 | 19 | 21 |
| Baseline (BL; n=24, 24, 19, 21) |
8.5
(6.75)
|
9.3
(8.80)
|
8.7
(7.55)
|
11.6
(10.71)
|
| Change from BL at Week 4 (n=23, 23, 18, 15) |
-2.5
(4.71)
|
-2.5
(3.72)
|
-0.5
(3.71)
|
-2.8
(3.88)
|
| Change from BL at Week 8 (n=19, 22, 17, 13) |
-1.4
(5.52)
|
-3.5
(4.94)
|
-2.4
(5.26)
|
-4.7
(8.89)
|
| Change from BL at Week 12 (n=19, 21, 17, 12) |
-0.9
(6.27)
|
-3.9
(4.74)
|
-2.5
(4.32)
|
-5.0
(6.90)
|
| Change from BL at Endpoint (n=24, 24, 19, 19) |
-2.3
(6.44)
|
-3.4
(4.60)
|
-2.5
(4.07)
|
-2.5
(7.12)
|
| Title | Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 12 and Endpoint (Last Postbaseline Observation Up to Week 12) |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 12, Endpoint (last postbaseline observation, up to Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (all participants who received 1 or more doses of study drug with ≥1 postbaseline primary efficacy assessment); n=number of participants with data at given time point. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 29 | 28 | 27 |
| Baseline (BL; n=29, 29, 28, 27) |
14.8
(2.83)
|
14.3
(2.61)
|
15.1
(2.54)
|
16.1
(3.82)
|
| Change from BL at Week 12 (n=23, 26, 22, 16) |
-5.0
(6.12)
|
-4.6
(5.30)
|
-6.5
(4.40)
|
-9.2
(4.90)
|
| Change from BL at Endpoint (n=27, 28, 26, 23) |
-5.1
(5.93)
|
-4.5
(5.15)
|
-6.1
(4.52)
|
-7.0
(5.61)
|
| Title | 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) |
|---|---|
| Description | 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. |
| Time Frame | Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set (all participants who received 1 or more doses of study drug); n=all participants with a nonmissing value at given time point. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 29 | 29 |
| Week 2 (n=14, 14, 13, 12) |
100
344.8%
|
100
333.3%
|
100
344.8%
|
100
344.8%
|
| Week 4 (n=13, 16, 15, 11) |
100
344.8%
|
100
333.3%
|
100
344.8%
|
100
344.8%
|
| Week 8 (n=13, 15, 13, 10) |
100
344.8%
|
100
333.3%
|
100
344.8%
|
100
344.8%
|
| Week 12 (n=14, 15, 13, 9) |
100
344.8%
|
100
333.3%
|
100
344.8%
|
100
344.8%
|
| Endpoint (n=19, 18, 16, 15) |
100
344.8%
|
100
333.3%
|
100
344.8%
|
100
344.8%
|
| Title | 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) |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Weeks 2, 4, 8, 12, and Endpoint (last postbaseline observation up to 12 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set (participants who received 1 or more doses of study drug) with a baseline S-HAM-D6 measurement; n=number of participants with nonmissing data at given time point. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 13 | 13 | 11 | 13 |
| Baseline (BL; n=13, 13, 11, 13) |
1.3
(1.49)
|
1.8
(1.07)
|
1.2
(1.72)
|
1.5
(1.33)
|
| Change from BL at Week 2 (n=13, 13, 11, 11) |
-0.7
(1.38)
|
-0.5
(2.63)
|
0.3
(1.49)
|
0.4
(1.29)
|
| Change from BL at Week 4 (n=12, 12, 11, 10) |
-0.5
(1.62)
|
0.9
(2.68)
|
-0.2
(1.47)
|
0.2
(2.97)
|
| Change from BL at Week 8 (n=10, 11, 10, 9) |
0.1
(1.60)
|
1.1
(4.68)
|
-0.2
(1.40)
|
1.6
(3.05)
|
| Change from BL at Week 12 (n=9, 10, 9, 8) |
0.9
(2.80)
|
0.2
(2.74)
|
1.0
(2.65)
|
-0.1
(2.17)
|
| Change from BL at Endpoint (n=13, 13, 11, 13) |
0.5
(2.54)
|
-0.1
(2.43)
|
0.6
(2.54)
|
0.9
(4.41)
|
| 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 | 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. |
| Time Frame | Baseline, Weeks 2, 4, 12, and Endpoint (last postbaseline observation up to 12 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (all participants who received 1 or more doses of study drug); n=number of participants with data at given time point. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 29 | 29 |
| Baseline (BL; n=29, 30, 29, 29) |
442.3
(19.60)
|
442.4
(18.38)
|
442.0
(19.07)
|
442.8
(19.16)
|
| Change from BL at Week 2 (n=28, 29, 27, 24) |
-4.4
(29.62)
|
5.8
(27.14)
|
-3.9
(38.10)
|
-8.8
(41.85)
|
| Change from BL at Week 4 (n=26, 28, 26, 21) |
-16.9
(78.81)
|
2.9
(34.50)
|
4.0
(41.32)
|
-21.6
(51.18)
|
| Change from BL at Week 12 (n=22, 26, 22, 15) |
-0.5
(24.39)
|
8.3
(20.46)
|
-18.3
(62.26)
|
-33.1
(55.65)
|
| Change from BL at Endpoint (n=29, 30, 27, 26) |
-10.1
(35.75)
|
6.6
(21.37)
|
-19.7
(60.53)
|
-21.2
(46.77)
|
| Title | 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) |
|---|---|
| Description | 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. |
| Time Frame | Weeks 4, 8, and 12 (or last postbaseline observation, up to Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the limited samples available for measurement of concentrations of antidepressants in the study, the plasma concentrations of antidepressants were not measured. The planned pharmacokinetic evaluation of the impact of armodafinil treatment on the pharmacokinetics of selective antidepressants was not conducted. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Concomitant Medication Usage In ≥5% of Participants Throughout the Study |
|---|---|
| Description | 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%. |
| Time Frame | Screening through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 29 | 29 |
| Analgesics |
4
13.8%
|
4
13.3%
|
7
24.1%
|
6
20.7%
|
| Antibacterials |
2
6.9%
|
2
6.7%
|
1
3.4%
|
2
6.9%
|
| Antihistamines for systemic use |
1
3.4%
|
2
6.7%
|
4
13.8%
|
2
6.9%
|
| Anti-inflammatory and antirheumatic products |
8
27.6%
|
9
30%
|
5
17.2%
|
8
27.6%
|
| Drugs for acid-related disorders |
0
0%
|
2
6.7%
|
2
6.9%
|
2
6.9%
|
| Lipid-modifying agents |
2
6.9%
|
8
26.7%
|
2
6.9%
|
2
6.9%
|
| Nasal preparations |
2
6.9%
|
3
10%
|
1
3.4%
|
2
6.9%
|
| Sex hormones and modulators of the genital system |
3
10.3%
|
4
13.3%
|
3
10.3%
|
3
10.3%
|
| Unspecified herbal |
1
3.4%
|
3
10%
|
1
3.4%
|
1
3.4%
|
| Vitamins/nutritional supplement |
5
17.2%
|
7
23.3%
|
4
13.8%
|
7
24.1%
|
| Title | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Withdrawals Due to AEs |
|---|---|
| Description | 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. |
| Time Frame | Screening through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (all participants who received 1 or more doses of study drug). |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 29 | 29 |
| Any adverse event |
14
48.3%
|
15
50%
|
16
55.2%
|
16
55.2%
|
| Severe adverse events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Treatment-related adverse events |
8
27.6%
|
9
30%
|
14
48.3%
|
15
51.7%
|
| Deaths |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Other serious adverse events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Withdrawn from study due to adverse events |
0
0%
|
2
6.7%
|
1
3.4%
|
5
17.2%
|
| Protocol-defined adverse event |
0
0%
|
1
3.3%
|
0
0%
|
3
10.3%
|
| Title | Number of Participants With Clinically Significant Abnormal Postbaseline Serum Chemistry Values |
|---|---|
| Description | 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. |
| Time Frame | Baseline, last postbaseline observation up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with a baseline and postbaseline measurement. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 28 | 28 |
| BUN >=10.71 mmol/L |
1
3.4%
|
0
0%
|
0
0%
|
0
0%
|
| Uric acid >=625 (men) or >=506 (women) μmol/L |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
| AST >=3 x upper limit of normal |
0
0%
|
0
0%
|
1
3.4%
|
0
0%
|
| GGT >=3 x upper limit of normal |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
| Total bilirubin >=34.2 μmol/L |
0
0%
|
1
3.3%
|
1
3.4%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Abnormal Postbaseline Hematology Values |
|---|---|
| Description | 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. |
| Time Frame | Baseline, last postbaseline observation up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with a baseline and postbaseline measurement. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 28 | 28 |
| WBC <=3.0 x 10^9/L |
1
3.4%
|
1
3.3%
|
1
3.4%
|
0
0%
|
| ANC <=1.0 x 10^9/L |
1
3.4%
|
0
0%
|
0
0%
|
0
0%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with a baseline and postbaseline measurement. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 28 | 28 |
| Number [participants] |
2
6.9%
|
1
3.3%
|
1
3.4%
|
1
3.4%
|
| Title | Number of Participants With Clinically Significant Abnormal Vital Sign Values |
|---|---|
| Description | 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. |
| Time Frame | Baseline, last postbaseline observation up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with a baseline and postbaseline measurement. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 28 | 29 |
| Heart Rate |
0
0%
|
1
3.3%
|
1
3.4%
|
0
0%
|
| Sitting Systolic Blood Pressure |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
| Sitting Diastolic Blood Pressure |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Notable Blood Pressure Values Per World Health Organization Criteria |
|---|---|
| Description | 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. |
| Time Frame | Baseline, last postbaseline observation up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with a baseline and postbaseline measurement. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 28 | 29 |
| Sitting Systolic Blood Pressure |
0
0%
|
1
3.3%
|
1
3.4%
|
2
6.9%
|
| Sitting Diastolic Blood Pressure |
0
0%
|
2
6.7%
|
0
0%
|
2
6.9%
|
| Title | Electrocardiogram (ECG) Findings Shifts From Baseline to Overall |
|---|---|
| Description | 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. |
| Time Frame | Baseline through Endpoint (last postbaseline observation, up to Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with a baseline and postbaseline measurement are summarized. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 28 | 27 | 27 | 27 |
| Normal at BL → Normal Overall |
15
51.7%
|
16
53.3%
|
14
48.3%
|
15
51.7%
|
| Normal at BL → Abnormal Overall |
1
3.4%
|
2
6.7%
|
4
13.8%
|
1
3.4%
|
| Abnormal at BL → Normal Overall |
3
10.3%
|
3
10%
|
7
24.1%
|
3
10.3%
|
| Abnormal at BL → Abnormal Overall |
9
31%
|
6
20%
|
2
6.9%
|
8
27.6%
|
| Title | Physical Examination Findings Shifts From Baseline to Endpoint (Last Postbaseline Observation, up to Week 12) |
|---|---|
| Description | 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. |
| Time Frame | Baseline through Endpoint (last postbaseline observation, up to Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| For each category, only participants in the Safety Analysis Set with a baseline and postbaseline measurement are summarized. |
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day |
|---|---|---|---|---|
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) |
| Measure Participants | 29 | 30 | 29 | 29 |
| General Appearance: Normal at BL → Normal at EP |
26
89.7%
|
27
90%
|
26
89.7%
|
27
93.1%
|
| General Appearance: Normal at BL → Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| General Appearance: Abnormal at BL → Normal at EP |
0
0%
|
2
6.7%
|
1
3.4%
|
0
0%
|
| General Appearance:Abnormal at BL → Abnormal at EP |
2
6.9%
|
0
0%
|
0
0%
|
0
0%
|
| HEENT: Normal at BL→ Normal at EP |
26
89.7%
|
29
96.7%
|
24
82.8%
|
26
89.7%
|
| HEENT: Normal at BL→ Abnormal at EP |
1
3.4%
|
0
0%
|
1
3.4%
|
0
0%
|
| HEENT: Abnormal at BL→ Normal at BL |
0
0%
|
0
0%
|
1
3.4%
|
0
0%
|
| HEENT: Abnormal at BL→ Abnormal at EP |
1
3.4%
|
0
0%
|
1
3.4%
|
1
3.4%
|
| Chest/Lungs: Normal at BL→ Normal at EP |
28
96.6%
|
29
96.7%
|
27
93.1%
|
27
93.1%
|
| Chest/Lungs: Normal at BL→ Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Chest/Lungs: Abnormal at BL→ Normal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Chest/Lungs: Abnormal at BL→ Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Heart: Normal at BL → Normal at EP |
26
89.7%
|
29
96.7%
|
27
93.1%
|
26
89.7%
|
| Heart: Normal at BL → Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
1
3.4%
|
| Heart: Abnormal at BL → Normal at EP |
2
6.9%
|
0
0%
|
0
0%
|
0
0%
|
| Heart: Abnormal at BL → Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Abdomen: Normal at BL → Normal at EP |
27
93.1%
|
27
90%
|
26
89.7%
|
26
89.7%
|
| Abdomen: Normal at BL → Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Abdomen: Abnormal at BL → Normal at EP |
0
0%
|
2
6.7%
|
1
3.4%
|
0
0%
|
| Abdomen: Abnormal at BL → Abnormal at EP |
1
3.4%
|
0
0%
|
0
0%
|
0
0%
|
| Musculoskeletal: Normal at BL → Normal at EP |
27
93.1%
|
29
96.7%
|
25
86.2%
|
27
93.1%
|
| Musculoskeletal: Normal at BL → Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Musculoskeletal: Abnormal at BL → Normal at EP |
1
3.4%
|
0
0%
|
1
3.4%
|
0
0%
|
| Musculoskeletal: Abnormal at BL → Abnormal at EP |
0
0%
|
0
0%
|
1
3.4%
|
0
0%
|
| Skin: Normal at BL → Normal at EP |
25
86.2%
|
24
80%
|
24
82.8%
|
24
82.8%
|
| Skin: Normal at BL → Abnormal at EP |
0
0%
|
1
3.3%
|
0
0%
|
1
3.4%
|
| Skin: Abnormal at BL → Normal at EP |
0
0%
|
1
3.3%
|
0
0%
|
1
3.4%
|
| Skin: Abnormal at BL → Abnormal at EP |
3
10.3%
|
3
10%
|
3
10.3%
|
1
3.4%
|
| Lymph Nodes: Normal at BL → Normal at EP |
25
86.2%
|
26
86.7%
|
24
82.8%
|
27
93.1%
|
| Lymph Nodes: Normal at BL → Abnormal at EP |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
| Lymph Nodes: Abnormal at BL → Normal at EP |
0
0%
|
0
0%
|
1
3.4%
|
0
0%
|
| Lymph Nodes: Abnormal at BL → Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Neurological: Normal at BL → Normal at EP |
26
89.7%
|
28
93.3%
|
27
93.1%
|
27
93.1%
|
| Neurological: Normal at BL → Abnormal at EP |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Neurological: Abnormal at BL → Normal at EP |
0
0%
|
1
3.3%
|
0
0%
|
0
0%
|
| Neurological: Abnormal at BL → Abnormal at EP |
2
6.9%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Screening through Week 12 | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day | ||||
| Arm/Group Description | Oral placebo tablets, once daily (QD) | Oral armodafinil 50 mg tablets, once daily (QD) | Oral armodafinil 150 mg tablets, once daily (QD) | Oral armodafinil 250 mg tablets, once daily (QD) | ||||
All Cause Mortality |
||||||||
| Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo | Armodafinil 50 mg/Day | Armodafinil 150 mg/Day | Armodafinil 250 mg/Day | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/29 (48.3%) | 15/30 (50%) | 16/29 (55.2%) | 16/29 (55.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Lymphadenopathy | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Cardiac disorders | ||||||||
| Palpitations | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Eye disorders | ||||||||
| Vision blurred | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Conjunctival haemorrhage | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea | 0/29 (0%) | 3/30 (10%) | 3/29 (10.3%) | 3/29 (10.3%) | ||||
| Diarrhoea | 1/29 (3.4%) | 1/30 (3.3%) | 0/29 (0%) | 3/29 (10.3%) | ||||
| Dry mouth | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 2/29 (6.9%) | ||||
| Abdominal discomfort | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Abdominal pain | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Gastroesophageal reflux disease | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Toothache | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| General disorders | ||||||||
| Feeling jittery | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 2/29 (6.9%) | ||||
| Fatigue | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Feeling abnormal | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Irritability | 1/29 (3.4%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Pyrexia | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Infections and infestations | ||||||||
| Upper respiratory tract infection | 1/29 (3.4%) | 1/30 (3.3%) | 3/29 (10.3%) | 0/29 (0%) | ||||
| Sinusitis | 1/29 (3.4%) | 1/30 (3.3%) | 0/29 (0%) | 2/29 (6.9%) | ||||
| Influenza | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Nasopharyngitis | 0/29 (0%) | 1/30 (3.3%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Pharyngitis | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Pharyngitis streptococcal | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Rhinitis | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Urinary tract infection | 1/29 (3.4%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Kidney infection | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Pneumonia | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Viral infection | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Arthropod sting | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Contusion | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Investigations | ||||||||
| Blood creatine phosphokinase increased | 1/29 (3.4%) | 1/30 (3.3%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Heart rate increased | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Alanine aminotransferase increased | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Blood alkaline phosphatase increased | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Blood bicarbonate decreased | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Blood potassium increased | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Blood pressure increased | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Blood sodium increased | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Platelet count decreased | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Weight decreased | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Weight increased | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Blood creatinine increased | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Electrocardiogram T wave abnormal | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Glucose urine present | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 1/29 (3.4%) | ||||
| Hyperglycaemia | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Flank pain | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Musculoskeletal pain | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Back pain | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Nervous system disorders | ||||||||
| Headache | 2/29 (6.9%) | 5/30 (16.7%) | 5/29 (17.2%) | 5/29 (17.2%) | ||||
| Dizziness | 0/29 (0%) | 2/30 (6.7%) | 1/29 (3.4%) | 2/29 (6.9%) | ||||
| Memory impairment | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Sinus headache | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Somnolence | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Pregnancy, puerperium and perinatal conditions | ||||||||
| Unintended pregnancy | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/29 (0%) | 4/30 (13.3%) | 0/29 (0%) | 3/29 (10.3%) | ||||
| Insomnia | 1/29 (3.4%) | 1/30 (3.3%) | 3/29 (10.3%) | 1/29 (3.4%) | ||||
| Bruxism | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 1/29 (3.4%) | ||||
| Depression | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 2/29 (6.9%) | ||||
| Initial insomnia | 0/29 (0%) | 1/30 (3.3%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Logorrhoea | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Middle insomnia | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Tachyphrenia | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Abnormal dreams | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Nightmare | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Pressure of speech | 1/29 (3.4%) | 0/30 (0%) | 0/29 (0%) | 0/29 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Dyspnoea | 0/29 (0%) | 0/30 (0%) | 1/29 (3.4%) | 0/29 (0%) | ||||
| Oropharyngeal pain | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis contact | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 2/29 (6.9%) | ||||
| Eczema | 0/29 (0%) | 1/30 (3.3%) | 0/29 (0%) | 0/29 (0%) | ||||
| Skin irritation | 0/29 (0%) | 0/30 (0%) | 0/29 (0%) | 1/29 (3.4%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
| Name/Title | Manager, Biopharmaceutics |
|---|---|
| Organization | Teva Pharmaceuticals USA |
| Phone | 1-866-384-5525 |
| clinicaltrialqueries@tevausa.com |
- C10953/3067/ES/MN