Study to Evaluate the Safety, Tolerability, and Efficacy of Armodafinil as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury
- Registration Number
- NCT00983437
- Lead Sponsor
- Cephalon, Inc.
- Brief Summary
The primary objective of this study is to evaluate the safety and tolerability of long-term (12 months) armodafinil treatment in patients with excessive sleepiness associated with mild or moderate closed traumatic brain injury (TBI).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Armodafinil Armodafinil Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
- Primary Outcome Measures
Name Time Method Safety and Tolerability: Concomitant Medication Usage In Participants Throughout the Study Assessed from Screening through end of treatment; median (full range) of treatment was 98 (5.0 to 326.0) days. Therapeutic classification of concomitant medications used by participants throughout the study. Participants are counted only once in each therapeutic class category.
Safety and Tolerability: Number of Participants With Clinically Significant Serum Chemistry Test Results Assessed at Screening, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days. 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.
Safety and Tolerability: Number of Participants With Clinically Significant Abnormal Vital Signs Measurements 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. 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.
Safety and Tolerability: Number of Participants With Clinically Significant Abnormal Urinalysis Results Baseline, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days. 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.
Safety and Tolerability: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs Assessed from Screening through end of treatment; median (full range) of treatment was 98 (5.0 to 326.0) days. 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).
Safety and Tolerability: Physical Examination Findings Shifts From Baseline to Endpoint (Month 12 or Last Postbaseline Observation) Baseline through Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days. 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.
Change From Baseline in the Total Score From the Self-Reported Hamilton Depression Rating Scale, 6 Item Version (S-HAM-D6) at Week 2, Months 1, 2, 3, 6, 9, and Endpoint (Month 12, or Last Postbaseline Observation) 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. 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.
Safety and Tolerability: Number of Participants With Clinically Significant Abnormal Hematology Test Results Assessed at Screening, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days. 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.
Safety and Tolerability: Number of Participants With Notable Blood Pressure Values Per World Health Organization Criteria 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. 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.
Number of Participants Answering "Yes" to Any Question on the Columbia-Suicide Severity Rating Scale Since Last Visit Version (C-SSRS SLV) at Week 2, Months 1, 2, 3, 6, 9, and Endpoint (Month 12, or Last Postbaseline Observation) 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. 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.
Safety and Tolerability: Electrocardiogram (ECG) Findings Shifts From Baseline to Overall Baseline through Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days. 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Improvement on the Clinical Global Impression of Severity of Illness (CGI-S) at Week 2 and Months 1, 2, 3, 6, 9, and Endpoint (Month 12 or Last Postbaseline Observation) 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. 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.
Change From Baseline in the Medical Outcomes Study 6-Item Cognitive Functioning Scale (MOS-CF6) Total Score at Months 3, 6, 9, and Endpoint (Month 12 or Last Postbaseline Observation) Baseline, Months 3, 6, 9, and 12 (or last postbaseline observation) The MOS-CF 6 is an instrument to assess patient self-reported cognitive function. Items were selected to cover 6 relevant aspects of cognitive functioning as follows: confusion, concentration/thinking, attention, memory, reasoning, problem solving, and processing speed. The CF 6-item responses include 6 choices, ranging from "none of the time" to "all of the time." The CF-6 is scored by summing responses across the 6 items and converting the total to a 0- to 100-point scale, with higher scores indicating better cognitive functioning. 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.
Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 2 and Months 1, 2, 3, 6, 9, and Endpoint (Month 12 or Last Postbaseline Observation) 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. 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.
Change From Baseline in Traumatic Brain Injury - Work Instability Scale (TBI-WIS) Score Values at Months 3, 6, 9, and Endpoint (Month 12 or Last Postbaseline Observation) 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. 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.
Change From Baseline in Clinical Global Impression of Severity of Illness (CGI-S) at Week 2 and Months 1, 2, 3, 6, 9, and Endpoint (Month 12 or Last Postbaseline Observation) 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. 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.
Trial Locations
- Locations (61)
Teva Investigational Site 8
🇺🇸Houston, Texas, United States
Teva Investigational Site 20
🇺🇸Houston, Texas, United States
Teva Investigational Site 1
🇺🇸Orlando, Florida, United States
Teva Investigational Site 52
🇺🇸Hallandale Beach, Florida, United States
Teva Investigational Site 69
🇺🇸Wallingford, Connecticut, United States
Teva Investigational Site 12
🇺🇸Atlanta, Georgia, United States
Teva Investigational Site 65
🇺🇸Columbia, South Carolina, United States
Teva Investigational Site 25
🇺🇸Dallas, Texas, United States
Teva Investigational Site 59
🇺🇸Chicago, Illinois, United States
Teva Investigational Site 60
🇺🇸Austin, Texas, United States
Teva Investigational Site 18
🇺🇸Pembroke Pines, Florida, United States
Teva Investigational Site 28
🇺🇸Danville, Indiana, United States
Teva Investigational Site 46
🇺🇸Chicago, Illinois, United States
Teva Investigational Site 19
🇺🇸Fort Wayne, Indiana, United States
Teva Investigational Site 45
🇺🇸Winston-Salem, North Carolina, United States
Teva Investigational Site 30
🇺🇸Toledo, Ohio, United States
Teva Investigational Site 35
🇺🇸Midvale, Utah, United States
Teva Investigational Site 13
🇺🇸Jefferson Hills, Pennsylvania, United States
Teva Investigational Site 47
🇺🇸Miami, Florida, United States
Teva Investigational Site 55
🇺🇸San Diego, California, United States
Teva Investigational Site 33
🇺🇸San Diego, California, United States
Teva Investigational Site 31
🇺🇸Cincinnati, Ohio, United States
Teva Investigational Site 34
🇺🇸Cincinnati, Ohio, United States
Teva Investigational Site 9
🇺🇸Shawnee Mission, Kansas, United States
Teva Investigational Site 58
🇺🇸Birmingham, Alabama, United States
Teva Investigational Site 11
🇺🇸Durham, North Carolina, United States
Teva Investigational Site 3
🇺🇸Oklahoma City, Oklahoma, United States
Teva Investigational Site 23
🇺🇸San Antonio, Texas, United States
Teva Investigational Site 5
🇺🇸Little Rock, Arkansas, United States
Teva Investigational Site 62
🇺🇸Tucson, Arizona, United States
Teva Investigational Site 10
🇺🇸Spring Hill, Florida, United States
Teva Investigational Site 67
🇺🇸Macon, Georgia, United States
Teva Investigational Site 15
🇺🇸Suwanee, Georgia, United States
Teva Investigational Site 54
🇺🇸Chicago, Illinois, United States
Teva Investigational Site 2
🇺🇸Indianapolis, Indiana, United States
Teva Investigational Site 32
🇺🇸Chevy Chase, Maryland, United States
Teva Investigational Site 37
🇺🇸Belmont, Massachusetts, United States
Teva Investigational Site 22
🇺🇸Saginaw, Michigan, United States
Teva Investigational Site 7
🇺🇸Hattiesburg, Mississippi, United States
Teva Investigational Site 56
🇺🇸Lincoln, Nebraska, United States
Teva Investigational Site 42
🇺🇸Saint Louis, Missouri, United States
Teva Investigational Site 64
🇺🇸Clarks Summit, Pennsylvania, United States
Teva Investigational Site 61
🇺🇸Germantown, Tennessee, United States
Teva Investigational Site 50
🇺🇸West Allis, Wisconsin, United States
Teva Investigational Site 49
🇺🇸La Palma, California, United States
Teva Investigational Site 51
🇺🇸La Palma, California, United States
Teva Investigational Site 17
🇺🇸Tampa, Florida, United States
Teva Investigational Site 44
🇺🇸Fountain Valley, California, United States
Teva Investigational Site 53
🇺🇸Santa Monica, California, United States
Teva Investigational Site 38
🇺🇸Saint Petersburg, Florida, United States
Teva Investigational Site 14
🇺🇸Atlanta, Georgia, United States
Teva Investigational Site 39
🇺🇸Indianapolis, Indiana, United States
Teva Investigational Site 41
🇺🇸Iowa City, Iowa, United States
Teva Investigational Site 48
🇺🇸Louisville, Kentucky, United States
Teva Investigational Site 36
🇺🇸West Seneca, New York, United States
Teva Investigational Site 63
🇺🇸New York, New York, United States
Teva Investigational Site 24
🇺🇸Richmond, Virginia, United States
Teva Investigational Site 68
🇺🇸Gainesville, Georgia, United States
Teva Investigational Site 57
🇺🇸Middleburg Heights, Ohio, United States
Teva Investigational Site 66
🇺🇸Midvale, Utah, United States
Teva Investigational Site 16
🇺🇸Hot Springs, Arkansas, United States