modafinil has been researched along with Closed Head Injuries in 1 studies
Modafinil: A benzhydryl acetamide compound, central nervous system stimulant, and CYP3A4 inducing agent that is used in the treatment of NARCOLEPSY and SLEEP WAKE DISORDERS.
modafinil : A racemate comprising equimolar amounts of armodafinil and (S)-modafinil. A central nervous system stimulant, it is used for the treatment of sleeping disorders such as narcolepsy, obstructive sleep apnoea, and shift-work sleep disorder. The optical enantiomers of modafinil have similar pharmacological actions in animals.
2-[(diphenylmethyl)sulfinyl]acetamide : A sulfoxide that is dimethylsulfoxide in which two hydrogens attached to one of the methyl groups are replaced by phenyl groups, while one hydrogen attached to the other methyl group is replaced by a carbamoyl (aminocarbonyl) group.
Excerpt | Relevance | Reference |
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"Armodafinil was generally well tolerated, with headache the most common adverse event in both double-blind and open-label portions." | 2.79 | 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. ( Lankford, A; Menn, SJ; Yang, R, 2014) |
Timeframe | Studies, this research(%) | All Research% |
---|---|---|
pre-1990 | 0 (0.00) | 18.7374 |
1990's | 0 (0.00) | 18.2507 |
2000's | 0 (0.00) | 29.6817 |
2010's | 1 (100.00) | 24.3611 |
2020's | 0 (0.00) | 2.80 |
Authors | Studies |
---|---|
Menn, SJ | 1 |
Yang, R | 1 |
Lankford, A | 1 |
Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
---|---|---|---|---|---|---|---|
A 12-Month, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Armodafinil (150 and 250 mg/Day) as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury[NCT00983437] | Phase 3 | 49 participants (Actual) | Interventional | 2009-08-31 | Terminated (stopped due to Study has been stopped by sponsor decision) | ||
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 C[NCT00893789] | Phase 3 | 117 participants (Actual) | Interventional | 2009-04-30 | Terminated (stopped due to Study has been stopped by sponsor decision.) | ||
[information is prepared from clinicaltrials.gov, extracted Sep-2024] |
Criteria for clinically significant abnormal hematology values: hematocrit, men <0.37 L/L or women <0.32 L/L; hemoglobin, men ≤115 g/L or women ≤95 g/L; white blood cell (WBC) count ≤3x10^9/L or ≥20x10^9/L; eosinophils ≥10%; absolute neutrophil count (ANC) ≤1x10^9/L; platelet count ≤75x10^9/L or ≥700x10^9/L. (NCT00983437)
Timeframe: Assessed at Screening, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) |
---|---|
Armodafinil | 0 |
Criteria for clinically significant abnormal urinalysis values: blood (hemoglobin) ≥2 unit increase from baseline; glucose ≥2 unit increase from baseline; ketones ≥2 unit increase from baseline; total protein ≥2 unit increase from baseline. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study. (NCT00983437)
Timeframe: Baseline, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) |
---|---|
Armodafinil | 0 |
Criteria for clinically significant abnormal vital signs values: pulse, ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm or ≤50 bpm and decrease from baseline of ≥15 bpm; systolic blood pressure, ≥180 mm Hg and increase from baseline of ≥20 mm Hg or ≤90 mm Hg and decrease from baseline of ≥20 mm Hg; diastolic blood pressure, ≥105 mm Hg and increase from baseline of ≥15 mm Hg or ≤50 mm Hg and decrease from baseline of ≥15 mm Hg; temperature >38.3º celsius (C) and change from baseline of ≥1.1°C. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study. (NCT00983437)
Timeframe: Baseline, Week 2, Months 1, 2, 3, 6, 9, and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) |
---|---|
Armodafinil | 0 |
The percentage of participants answering 'yes' to any of the 9 yes/no questions about suicidal behaviors, ideations, and acts at given time points are presented. The C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors since last visit (SLV). Questions included the presence (yes) or absence (no) 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. (NCT00983437)
Timeframe: Week 2, Months 1, 2, 3, 6, 9, and Endpoint (Month 12, or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) | |||||||
---|---|---|---|---|---|---|---|---|
Week 2 (n=18), yes to any question | Month 1 (n=18), yes to any question | Month 2 (n=18), yes to any question | Month 3 (n=13), yes to any question | Month 6 (n=10), yes to any question | Month 9 (n=4), yes to any question | Endpoint (n=36), yes to 'Wish to Be Dead' question | Endpoint (n=36), yes to all other questions | |
Armodafinil | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
The clinician's rating of disease severity as assessed by the Clinical Global Impression of Severity (CGI-S). CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill); the 7 categories include the following: normal-shows no sign of illness, borderline ill, mildly (slightly) ill, moderately ill, markedly ill, severely ill, and among the most extremely ill. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study. (NCT00983437)
Timeframe: Baseline, Week 2 and Months 1, 2, 3, 6, 9, and Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | units on a scale (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
Baseline (BL; n=45) | Change from BL at Week 2 (n=41) | Change from BL at Month 1 (n=35) | Change from BL at Month 2 (n=30) | Change from BL at Month 3 (n=22) | Change from BL at Month 6 (n=11) | Change from BL at Month 9 (n=4) | Change from BL at Endpoint (n=45) | |
Armodafinil | 4.4 | -1.9 | -2.1 | -2.6 | -2.4 | -2.5 | -3.3 | -2.2 |
The participant'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. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study. (NCT00983437)
Timeframe: Baseline, Week 2 and Months 1, 2, 3, 6, 9, and Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | units on a scale (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
Baseline (BL; n=45) | Change from BL at Week 2 (n=41) | Change from BL at Month 1 (n=35) | Change from BL at Month 2 (n=30) | Change from BL at Month 3 (n=22) | Change from BL at Month 6 (n=11) | Change from BL at Month 9 (n=4) | Change from BL at Endpoint (n=45) | |
Armodafinil | 14.8 | -8.0 | -8.5 | -9.0 | -9.0 | -10.0 | -10.3 | -9.0 |
"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. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study." (NCT00983437)
Timeframe: Baseline, Week 2, Months 1, 2, 3, 6, 9, and Endpoint (Month 12, or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | units on a scale (Mean) | |||||||
---|---|---|---|---|---|---|---|---|
Baseline (BL; n=13) | Change from BL at Week 2 (n=13) | Change from BL at Month 1 (n=12) | Change from BL at Month 2 (n=9) | Change from BL at Month 3 (n=1) | Change from BL at Month 6 (n=0) | Change from BL at Month 9 (n=0) | Change from BL at Endpoint (n=13) | |
Armodafinil | 1.4 | 0.9 | 0.2 | 0.0 | -1.0 | NA | NA | 0.0 |
"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 for work instability is low; 2 to 23, the risk is medium; and >23, the risk is high. Score range is 0 (lowest risk for work instability) to 36 (highest risk for work instability). Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study." (NCT00983437)
Timeframe: Baseline, Months 3, 6, 9, and Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | units on a scale (Mean) | ||||
---|---|---|---|---|---|
Baseline (BL; n=34) | Change from BL at Month 3 (n=19) | Change from BL at Month 6 (n=10) | Change from BL at Month 9 (n=3) | Change from BL at Endpoint (n=34) | |
Armodafinil | 9.6 | -3.1 | -2.5 | -7.3 | -4.6 |
The clinician's rating of disease severity as assessed by the Clinical Global Impression of Severity (CGI-S). CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill); the 7 categories include the following: normal-shows no sign of illness, borderline ill, mildly (slightly) ill, moderately ill, markedly ill, severely ill, and among the most extremely ill. Improvement is defined as at least 1 point improvement from baseline. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study. (NCT00983437)
Timeframe: Week 2 and Months 1, 2, 3, 6, 9, and Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | percentage of participants (Number) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Improved at Week 2 (n=41) | Not Improved at Week 2 (n=41) | Improved at Month 1 (n=35) | Not Improved at Month 1 (n=35) | Improved at Month 2 (n=30) | Not Improved at Month 2 (n=30) | Improved at Month 3 (n=22) | Not Improved at Month 3 (n=22) | Improved at Month 6 (n=11) | Not Improved at Month 6 (n=11) | Improved at Month 9 (n=4) | Not Improved at Month 9 (n=4) | Improved at Endpoint (n=45) | Not Improved at Endpoint (n=45) | |
Armodafinil | 95 | 5 | 97 | 3 | 100 | 0 | 100 | 0 | 91 | 9 | 100 | 0 | 93 | 7 |
Therapeutic classification of concomitant medications used by participants throughout the study. Participants are counted only once in each therapeutic class category. (NCT00983437)
Timeframe: Assessed from Screening through end of treatment; median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) | ||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Participants receiving any concomitant medication | All other therapeutic products | Analgesics | Anesthetics | Anti-anemic preparations | Antibacterials for systemic use | Anti-emetics and antinauseants | Antigout preparations | Antihistamines for systemic use | Anti-inflammatory and antirheumatic products | Antimycotics for systemic use | Antithrombotic agents | Beta blocking agents | Cardiac therapy | Corticosteroids for systemic use | Cough and cold preparations | Drugs for acid-related disorders | Drugs for obstructive airway diseases | Drugs used in diabetes | General nutrients | Lipid-modifying agents | Nasal preparations | Other gynecologicals | Psychoanaleptics | Psycholeptics | Sex hormones and modulators of the genital system | Thyroid therapy | Unspecified herbal | Vitamins | |
Armodafinil | 39 | 1 | 10 | 1 | 1 | 4 | 1 | 1 | 4 | 16 | 1 | 1 | 1 | 1 | 1 | 2 | 3 | 3 | 1 | 1 | 11 | 4 | 2 | 1 | 2 | 7 | 1 | 4 | 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. Any ECG finding that was judged by the investigator as a clinically meaningful change (worsening) compared to baseline was recorded as an adverse event. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study. (NCT00983437)
Timeframe: Baseline through Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) | |||
---|---|---|---|---|
Normal at BL → Normal Overall | Normal at BL→ Abnormal Overall | Abnormal at BL→ Normal Overall | Abnormal at BL → Abnormal Overall | |
Armodafinil | 17 | 4 | 3 | 11 |
AE=any untoward medical occurrence 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 to study drug. Protocol-defined AEs=treatment-emergent adverse events associated with skin rash, hypersensitivity reaction, emergent suicidal ideation or suicide attempt, depression, psychosis, and seizure or suspected seizure were considered to be of potential clinical importance. DB=double-blind portion of the study (NCT00893789). (NCT00983437)
Timeframe: Assessed from Screening through end of treatment; median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) | |||||||
---|---|---|---|---|---|---|---|---|
Any AE | Severe AEs | Treatment-related AEs | Deaths | SAEs (Other Than Deaths) | Discontinuations (DCs) Due to AEs | Protocol-defined AEs | DCs due to AEs with onset during DB phase | |
Armodafinil | 29 | 0 | 17 | 0 | 1 | 7 | 3 | 2 |
Criteria for clinically significant abnormal serum chemistry values: alanine aminotransferase (ALT) ≥3x upper limit of normal (ULN); aspartate aminotransferase (AST) ≥3x ULN; alkaline phosphatase ≥3x ULN; gamma-glutamyl transpeptidase (GGT) ≥3x ULN; lactate dehydrogenase (LDH) ≥3x ULN; blood urea nitrogen (BUN) ≥10.71 mmol/L; creatinine ≥177 μmol/L; uric acid, men ≥625 μmol/L, women ≥506 μmol/L; bilirubin (total) ≥34.2 μmol/L. (NCT00983437)
Timeframe: Assessed at Screening, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) | ||
---|---|---|---|
Participants with at least 1 abnormality (overall) | Blood Urea Nitrogen >=10.71 | Uric Acid >=625 (male) or >=506 (female) µmol/L | |
Armodafinil | 3 | 2 | 1 |
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. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study. (NCT00983437)
Timeframe: Baseline, Week 2, Months 1, 2, 3, 6, 9, and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) | ||
---|---|---|---|
Participants with at least 1 notable BP value | Sitting systolic BP >=140 mm Hg + Increase >=10% | Sitting diastolic BP >=90 mm Hg + Increase >=10% | |
Armodafinil | 6 | 4 | 3 |
Number of participants with shifts from normal/abnormal physical examination findings at baseline (BL) to (→) normal/abnormal findings at endpoint (EP). 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. Baseline was defined as the baseline value from the double-blind study C10953/3067/ES/MN (NCT00893789) from which the participants entered into this open-label study. (NCT00983437)
Timeframe: Baseline through Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.
Intervention | participants (Number) | |||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
General Appearance: Normal at BL→Normal at EP | General Appearance: Normal at BL→ Abnormal at EP | General Appearance: Abnormal at BL→ Normal at EP | General Appearance: Abnormal at BL→Abnormal at EP | HEENT: Normal at BL→Normal at EP | HEENT: Normal at BL→Abnormal at EP | HEENT: Abnormal at BL→Normal at EP | HEENT: Abnormal at BL→Abnormal at EP | Chest/Lungs: Normal at BL→Normal at EP | Chest/Lungs: Normal at BL→Abnormal at EP | Chest/Lungs: Abnormal at BL→Normal at EP | Chest/Lungs: Abnormal at BL→Abnormal at EP | Heart: Normal at BL→Normal at EP | Heart: Normal at BL→Abnormal at EP | Heart: Abnormal at BL→Normal at EP | Heart: Abnormal at BL→Abnormal at EP | Abdomen: Normal at BL→Normal at EP | Abdomen: Normal at BL→Abnormal at EP | Abdomen: Abnormal at BL→Normal at EP | Abdomen: Abnormal at BL→Abnormal at EP | Musculoskeletal: Normal at BL→Normal at EP | Musculoskeletal: Normal at BL→Abnormal at EP | Musculoskeletal: Abnormal at BL→Normal at EP | Musculoskeletal: Abnormal at BL→Abnormal at EP | Skin: Normal at BL→Normal at EP | Skin: Normal at BL→Abnormal at EP | Skin: Abnormal at BL→Normal at EP | Skin: Abnormal at BL→Abnormal at EP | Lymph Nodes: Normal at BL→Normal at EP | Lymph Nodes: Normal at BL→Abnormal at EP | Lymph Nodes: Abnormal at BL→Normal at EP | Lymph Nodes: Abnormal at BL→Abnormal at EP | Neurological: Normal at BL→Normal at EP | Neurological: Normal at BL→Abnormal at EP | Neurological: Abnormal at BL→Normal at EP | Neurological: Abnormal at BL→Abnormal at EP | |
Armodafinil | 37 | 2 | 0 | 0 | 37 | 1 | 1 | 0 | 39 | 0 | 0 | 0 | 38 | 1 | 0 | 0 | 38 | 1 | 0 | 0 | 38 | 1 | 0 | 0 | 35 | 0 | 0 | 4 | 34 | 0 | 1 | 0 | 37 | 1 | 1 | 0 |
Participants with at least one clinically significant postbaseline urinalysis abnormality, specifically presented is blood (hemoglobin) in urine >=2 units increase from baseline. (NCT00893789)
Timeframe: Baseline, last postbaseline observation up to Week 12
Intervention | participants (Number) |
---|---|
Placebo | 2 |
Armodafinil 50 mg/Day | 1 |
Armodafinil 150 mg/Day | 1 |
Armodafinil 250 mg/Day | 1 |
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. (NCT00893789)
Timeframe: Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12)
Intervention | percentage of participants (Number) | ||||
---|---|---|---|---|---|
Week 2 (n=14, 14, 13, 12) | Week 4 (n=13, 16, 15, 11) | Week 8 (n=13, 15, 13, 10) | Week 12 (n=14, 15, 13, 9) | Endpoint (n=19, 18, 16, 15) | |
Armodafinil 150 mg/Day | 100 | 100 | 100 | 100 | 100 |
Armodafinil 250 mg/Day | 100 | 100 | 100 | 100 | 100 |
Armodafinil 50 mg/Day | 100 | 100 | 100 | 100 | 100 |
Placebo | 100 | 100 | 100 | 100 | 100 |
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. (NCT00893789)
Timeframe: Baseline, Week 12, Endpoint (last postbaseline observation, up to Week 12)
Intervention | units on a scale (Mean) | ||
---|---|---|---|
Baseline (BL; n=29, 29, 28, 27) | Change from BL at Week 12 (n=23, 26, 22, 16) | Change from BL at Endpoint (n=27, 28, 26, 23) | |
Armodafinil 150 mg/Day | 15.1 | -6.5 | -6.1 |
Armodafinil 250 mg/Day | 16.1 | -9.2 | -7.0 |
Armodafinil 50 mg/Day | 14.3 | -4.6 | -4.5 |
Placebo | 14.8 | -5.0 | -5.1 |
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. (NCT00893789)
Timeframe: Baseline, Weeks 4, 8, and 12
Intervention | minutes (Mean) | |||
---|---|---|---|---|
Baseline (BL; n=29, 29, 28, 27) | Change from BL at Week 4 (n=26, 29, 26, 20) | Change from BL at Week 8 (n=24, 27, 24, 17) | Change from BL at Week 12 (n=22, 26, 22, 15) | |
Armodafinil 150 mg/Day | 4.2 | 4.0 | 4.2 | 4.6 |
Armodafinil 250 mg/Day | 3.7 | 7.0 | 4.2 | 7.4 |
Armodafinil 50 mg/Day | 4.2 | 2.7 | 2.5 | 2.7 |
Placebo | 3.3 | 3.2 | 2.1 | 1.8 |
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. (NCT00893789)
Timeframe: Baseline, last postbaseline observation up to Week 12
Intervention | minutes (Mean) | |
---|---|---|
Baseline (BL; n=29, 29, 28, 27) | Change from BL at Endpoint (n=27, 29, 26, 21) | |
Armodafinil 150 mg/Day | 4.2 | 5.0 |
Armodafinil 250 mg/Day | 3.7 | 7.2 |
Armodafinil 50 mg/Day | 4.2 | 2.6 |
Placebo | 3.3 | 2.4 |
"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." (NCT00893789)
Timeframe: Baseline, Weeks 2, 4, 8, 12, and Endpoint (last postbaseline observation up to 12 weeks)
Intervention | units on a scale (Mean) | |||||
---|---|---|---|---|---|---|
Baseline (BL; n=13, 13, 11, 13) | Change from BL at Week 2 (n=13, 13, 11, 11) | Change from BL at Week 4 (n=12, 12, 11, 10) | Change from BL at Week 8 (n=10, 11, 10, 9) | Change from BL at Week 12 (n=9, 10, 9, 8) | Change from BL at Endpoint (n=13, 13, 11, 13) | |
Armodafinil 150 mg/Day | 1.2 | 0.3 | -0.2 | -0.2 | 1.0 | 0.6 |
Armodafinil 250 mg/Day | 1.5 | 0.4 | 0.2 | 1.6 | -0.1 | 0.9 |
Armodafinil 50 mg/Day | 1.8 | -0.5 | 0.9 | 1.1 | 0.2 | -0.1 |
Placebo | 1.3 | -0.7 | -0.5 | 0.1 | 0.9 | 0.5 |
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. (NCT00893789)
Timeframe: Baseline, Weeks 2, 4, 12, and Endpoint (last postbaseline observation up to 12 weeks)
Intervention | minutes (Mean) | ||||
---|---|---|---|---|---|
Baseline (BL; n=29, 30, 29, 29) | Change from BL at Week 2 (n=28, 29, 27, 24) | Change from BL at Week 4 (n=26, 28, 26, 21) | Change from BL at Week 12 (n=22, 26, 22, 15) | Change from BL at Endpoint (n=29, 30, 27, 26) | |
Armodafinil 150 mg/Day | 442.0 | -3.9 | 4.0 | -18.3 | -19.7 |
Armodafinil 250 mg/Day | 442.8 | -8.8 | -21.6 | -33.1 | -21.2 |
Armodafinil 50 mg/Day | 442.4 | 5.8 | 2.9 | 8.3 | 6.6 |
Placebo | 442.3 | -4.4 | -16.9 | -0.5 | -10.1 |
"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)." (NCT00893789)
Timeframe: Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12)
Intervention | units on a scale (Mean) | ||||
---|---|---|---|---|---|
Baseline (BL; n=24, 24, 19, 21) | Change from BL at Week 4 (n=23, 23, 18, 15) | Change from BL at Week 8 (n=19, 22, 17, 13) | Change from BL at Week 12 (n=19, 21, 17, 12) | Change from BL at Endpoint (n=24, 24, 19, 19) | |
Armodafinil 150 mg/Day | 8.7 | -0.5 | -2.4 | -2.5 | -2.5 |
Armodafinil 250 mg/Day | 11.6 | -2.8 | -4.7 | -5.0 | -2.5 |
Armodafinil 50 mg/Day | 9.3 | -2.5 | -3.5 | -3.9 | -3.4 |
Placebo | 8.5 | -2.5 | -1.4 | -0.9 | -2.3 |
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%. (NCT00893789)
Timeframe: Screening through Week 12
Intervention | participants (Number) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Analgesics | Antibacterials | Antihistamines for systemic use | Anti-inflammatory and antirheumatic products | Drugs for acid-related disorders | Lipid-modifying agents | Nasal preparations | Sex hormones and modulators of the genital system | Unspecified herbal | Vitamins/nutritional supplement | |
Armodafinil 150 mg/Day | 7 | 1 | 4 | 5 | 2 | 2 | 1 | 3 | 1 | 4 |
Armodafinil 250 mg/Day | 6 | 2 | 2 | 8 | 2 | 2 | 2 | 3 | 1 | 7 |
Armodafinil 50 mg/Day | 4 | 2 | 2 | 9 | 2 | 8 | 3 | 4 | 3 | 7 |
Placebo | 4 | 2 | 1 | 8 | 0 | 2 | 2 | 3 | 1 | 5 |
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. (NCT00893789)
Timeframe: Baseline through Endpoint (last postbaseline observation, up to Week 12)
Intervention | participants (Number) | |||
---|---|---|---|---|
Normal at BL → Normal Overall | Normal at BL → Abnormal Overall | Abnormal at BL → Normal Overall | Abnormal at BL → Abnormal Overall | |
Armodafinil 150 mg/Day | 14 | 4 | 7 | 2 |
Armodafinil 250 mg/Day | 15 | 1 | 3 | 8 |
Armodafinil 50 mg/Day | 16 | 2 | 3 | 6 |
Placebo | 15 | 1 | 3 | 9 |
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. (NCT00893789)
Timeframe: Screening through Week 12
Intervention | participants (Number) | ||||||
---|---|---|---|---|---|---|---|
Any adverse event | Severe adverse events | Treatment-related adverse events | Deaths | Other serious adverse events | Withdrawn from study due to adverse events | Protocol-defined adverse event | |
Armodafinil 150 mg/Day | 16 | 0 | 14 | 0 | 0 | 1 | 0 |
Armodafinil 250 mg/Day | 16 | 0 | 15 | 0 | 0 | 5 | 3 |
Armodafinil 50 mg/Day | 15 | 0 | 9 | 0 | 0 | 2 | 1 |
Placebo | 14 | 0 | 8 | 0 | 0 | 0 | 0 |
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. (NCT00893789)
Timeframe: Baseline, last postbaseline observation up to Week 12
Intervention | participants (Number) | |
---|---|---|
WBC <=3.0 x 10^9/L | ANC <=1.0 x 10^9/L | |
Armodafinil 150 mg/Day | 1 | 0 |
Armodafinil 250 mg/Day | 0 | 0 |
Armodafinil 50 mg/Day | 1 | 0 |
Placebo | 1 | 1 |
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. (NCT00893789)
Timeframe: Baseline, last postbaseline observation up to Week 12
Intervention | participants (Number) | ||||
---|---|---|---|---|---|
BUN >=10.71 mmol/L | Uric acid >=625 (men) or >=506 (women) μmol/L | AST >=3 x upper limit of normal | GGT >=3 x upper limit of normal | Total bilirubin >=34.2 μmol/L | |
Armodafinil 150 mg/Day | 0 | 0 | 1 | 0 | 1 |
Armodafinil 250 mg/Day | 0 | 0 | 0 | 0 | 0 |
Armodafinil 50 mg/Day | 0 | 1 | 0 | 1 | 1 |
Placebo | 1 | 0 | 0 | 0 | 0 |
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. (NCT00893789)
Timeframe: Baseline, last postbaseline observation up to Week 12
Intervention | participants (Number) | ||
---|---|---|---|
Heart Rate | Sitting Systolic Blood Pressure | Sitting Diastolic Blood Pressure | |
Armodafinil 150 mg/Day | 1 | 0 | 0 |
Armodafinil 250 mg/Day | 0 | 0 | 0 |
Armodafinil 50 mg/Day | 1 | 1 | 1 |
Placebo | 0 | 0 | 0 |
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. (NCT00893789)
Timeframe: Baseline, last postbaseline observation up to Week 12
Intervention | participants (Number) | |
---|---|---|
Sitting Systolic Blood Pressure | Sitting Diastolic Blood Pressure | |
Armodafinil 150 mg/Day | 1 | 0 |
Armodafinil 250 mg/Day | 2 | 2 |
Armodafinil 50 mg/Day | 1 | 2 |
Placebo | 0 | 0 |
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. (NCT00893789)
Timeframe: Last postbaseline observation up to Week 12
Intervention | percentage of participants (Number) | |
---|---|---|
Responders | Nonresponders | |
Armodafinil 150 mg/Day | 54 | 46 |
Armodafinil 250 mg/Day | 48 | 52 |
Armodafinil 50 mg/Day | 41 | 59 |
Placebo | 38 | 62 |
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. (NCT00893789)
Timeframe: Weeks 2, 4, 8, and 12
Intervention | percentage of participants (Number) | |||||||
---|---|---|---|---|---|---|---|---|
Week 2 Responders (n=28, 29, 27, 23) | Week 2 Nonresponders (n=28, 29, 27, 23) | Week 4 Responders (n=27, 29, 26, 20) | Week 4 Nonresponders (n=27, 29, 26, 20) | Week 8 Responders (n=23, 27, 24, 18) | Week 8 Nonresponders (n=23, 27, 24, 18) | Week 12 Responders (n=23, 26, 22, 16) | Week 12 Nonresponders (n=23, 26, 22, 16) | |
Armodafinil 150 mg/Day | 37 | 63 | 50 | 50 | 54 | 46 | 55 | 45 |
Armodafinil 250 mg/Day | 39 | 61 | 50 | 50 | 56 | 44 | 56 | 44 |
Armodafinil 50 mg/Day | 21 | 79 | 24 | 76 | 48 | 52 | 42 | 58 |
Placebo | 14 | 86 | 22 | 78 | 35 | 65 | 35 | 65 |
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. (NCT00893789)
Timeframe: Baseline through Endpoint (last postbaseline observation, up to Week 12)
Intervention | participants (Number) | |||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
General Appearance: Normal at BL → Normal at EP | General Appearance: Normal at BL → Abnormal at EP | General Appearance: Abnormal at BL → Normal at EP | General Appearance:Abnormal at BL → Abnormal at EP | HEENT: Normal at BL→ Normal at EP | HEENT: Normal at BL→ Abnormal at EP | HEENT: Abnormal at BL→ Normal at BL | HEENT: Abnormal at BL→ Abnormal at EP | Chest/Lungs: Normal at BL→ Normal at EP | Chest/Lungs: Normal at BL→ Abnormal at EP | Chest/Lungs: Abnormal at BL→ Normal at EP | Chest/Lungs: Abnormal at BL→ Abnormal at EP | Heart: Normal at BL → Normal at EP | Heart: Normal at BL → Abnormal at EP | Heart: Abnormal at BL → Normal at EP | Heart: Abnormal at BL → Abnormal at EP | Abdomen: Normal at BL → Normal at EP | Abdomen: Normal at BL → Abnormal at EP | Abdomen: Abnormal at BL → Normal at EP | Abdomen: Abnormal at BL → Abnormal at EP | Musculoskeletal: Normal at BL → Normal at EP | Musculoskeletal: Normal at BL → Abnormal at EP | Musculoskeletal: Abnormal at BL → Normal at EP | Musculoskeletal: Abnormal at BL → Abnormal at EP | Skin: Normal at BL → Normal at EP | Skin: Normal at BL → Abnormal at EP | Skin: Abnormal at BL → Normal at EP | Skin: Abnormal at BL → Abnormal at EP | Lymph Nodes: Normal at BL → Normal at EP | Lymph Nodes: Normal at BL → Abnormal at EP | Lymph Nodes: Abnormal at BL → Normal at EP | Lymph Nodes: Abnormal at BL → Abnormal at EP | Neurological: Normal at BL → Normal at EP | Neurological: Normal at BL → Abnormal at EP | Neurological: Abnormal at BL → Normal at EP | Neurological: Abnormal at BL → Abnormal at EP | |
Armodafinil 150 mg/Day | 26 | 0 | 1 | 0 | 24 | 1 | 1 | 1 | 27 | 0 | 0 | 0 | 27 | 0 | 0 | 0 | 26 | 0 | 1 | 0 | 25 | 0 | 1 | 1 | 24 | 0 | 0 | 3 | 24 | 0 | 1 | 0 | 27 | 0 | 0 | 0 |
Armodafinil 250 mg/Day | 27 | 0 | 0 | 0 | 26 | 0 | 0 | 1 | 27 | 0 | 0 | 0 | 26 | 1 | 0 | 0 | 26 | 0 | 0 | 0 | 27 | 0 | 0 | 0 | 24 | 1 | 1 | 1 | 27 | 0 | 0 | 0 | 27 | 0 | 0 | 0 |
Armodafinil 50 mg/Day | 27 | 0 | 2 | 0 | 29 | 0 | 0 | 0 | 29 | 0 | 0 | 0 | 29 | 0 | 0 | 0 | 27 | 0 | 2 | 0 | 29 | 0 | 0 | 0 | 24 | 1 | 1 | 3 | 26 | 1 | 0 | 0 | 28 | 0 | 1 | 0 |
Placebo | 26 | 0 | 0 | 2 | 26 | 1 | 0 | 1 | 28 | 0 | 0 | 0 | 26 | 0 | 2 | 0 | 27 | 0 | 0 | 1 | 27 | 0 | 1 | 0 | 25 | 0 | 0 | 3 | 25 | 0 | 0 | 0 | 26 | 0 | 0 | 2 |
1 trial available for modafinil and Closed Head Injuries
Article | Year |
---|---|
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.
Topics: Administration, Oral; Adolescent; Adult; Aged; Analysis of Variance; Benzhydryl Compounds; Brain Inj | 2014 |
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.
Topics: Administration, Oral; Adolescent; Adult; Aged; Analysis of Variance; Benzhydryl Compounds; Brain Inj | 2014 |
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.
Topics: Administration, Oral; Adolescent; Adult; Aged; Analysis of Variance; Benzhydryl Compounds; Brain Inj | 2014 |
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.
Topics: Administration, Oral; Adolescent; Adult; Aged; Analysis of Variance; Benzhydryl Compounds; Brain Inj | 2014 |