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

• Sponsor: Cephalon, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00983437
• Collaborator: (none)
• Enrollment: 49
• Locations: 61
• Arm: 1
• Actual Duration (Months): 17
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury	Drug: Armodafinil	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Aug 31, 2009
• Actual Primary Completion Date: Jan 31, 2011
• Actual Study Completion Date: Jan 31, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Armodafinil Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.	Drug: Armodafinil; Other Names: CEP-10953

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Patients enrolled in this study will be rollover patients (those who completed the previous double-blind efficacy study C10953/3067/ES/MN) and new patients (those who did not participate in the C10953/3067/ES/MN study).

Inclusion Criteria (for New Patients):

• The patient has a mild (Glasgow Coma Scale [GCS] score = 13-15) or moderate (GCS score = 9-12) closed traumatic brain injury (TBI) at the time of the injury, and the injury occurred 1 to 10 years prior to screening.

• The patient has a Glasgow Outcome Scale score of 5.

• The patient has an Epworth Sleepiness Scale (ESS) score of at least 10.

• The patient has a mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of 4 naps) of less than 8 minutes.

• The patient has a Clinical Global Impression of Severity of Illness (CGI-S) rating relating to their excessive sleepiness of 4 or more.

• The patient has 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 identified according to the first inclusion criterion.

• Written informed consent was obtained.

• If admitted to an in-patient treatment facility, the patient was discharged at least 1 month prior to the screening visit.

• The patient does 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 1 of those methods for the duration of the study (and for 30 days after participation in the study).

• The patient is 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 is willing and able to comply with study restrictions and attend regularly scheduled clinic visits as specified in the protocol.

• The patient has an 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 inhibitor [SSRIs] and serotonin and norepinephrine reuptake inhibitor [SNRIs]), 8 weeks (contraceptives), or 4 weeks (all other allowed medication) before the screening visit and is not likely to require a change in therapy for at least 12 weeks on the basis of the investigators' assessment.

• The patient has 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 has no other head injury fulfilling the criteria for TBI within ±1 year of the TBI identified according to the first inclusion criterion.

• The patient has a habitual bedtime between 2100 and 2400.

Inclusion Criteria (for Rollover Patients from Study C10953/3067/ES/MN):

• The patient has completed 12 weeks of double-blind treatment in Study C10953/3067/ES/MN.

• Written informed consent was obtained.

• Women of childbearing potential (not surgically sterile or 2 years postmenopausal), used a medically accepted method of contraception and agreed to continue use 1 of those methods for the duration of the study and for 30 days after participation in the study.

• The patient is in otherwise good health, as judged by the investigator, on the basis of a medical and psychiatric history, physical examination, ECG, serum chemistry, hematology, and urinalysis.

• The patient is willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and was willing to return to the clinic for the follow-up evaluation as specified in the protocol.

Exclusion Criteria (for New Patients):

• The patient has a history of 2 or more episodes of transient loss of consciousness without clear medical explanation, or has a history of known or suspected pseudo seizure (psychogenic seizure). Patients with a history of seizure or epilepsy may be eligible following discussion with the medical monitor.

• The patient requires, or is likely to require, treatment with anticonvulsant medication during the study; or has taken anticonvulsant medication within 6 months before the screening visit.

• The patient has an unstable or uncontrolled medical (including illnesses related to the cardiovascular, 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 has had neurosurgery involving the brain or brainstem.

• The patient has a history of schizophrenia, bipolar disorder, psychotic depression, or other psychotic episode.

• The patient has 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). Patients with any Axis II disorder, that in the opinion of the investigator, would affect patient participation in the study or full compliance with study procedures.

• The patient has a history of, or currently meets The International Classification of Sleep Disorders, Edition 2 (ICSD-2) criteria for any other sleep disorder associated with excessive daytime sleepiness; or the patient has a history of idiopathic hypersomnia, insomnia (requiring treatment), or sleep disorder before the development of the TBI.

• The patient has 85% or less sleep efficiency (sleep duration ÷ time in bed x 100%) as determined from Nocturnal Polysomnography (NPSG).

• The patient has any disorder that may have interfered with drug absorption, distribution, metabolism, or excretion.

• The patient has 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 is longer.

• The patient has a need for chronic pain medications.

• In the judgment of the investigator, the patient has a clinically significant deviation from normal in the physical examination.

• In the judgment of the investigator, the patient has any clinically significant ECG finding.

• The patient has a diagnosis of any type of dementia.

• The patient has a history of suicidal ideation (considered by the investigator to be of clinical significance), or is suicidal.

• The patient has a known hypersensitivity to armodafinil, racemic modafinil, or any component of the study drug tablets. Armodafinil tablets contained the following inactive ingredients: croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, and pregelatinized starch.

• The patient has 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 has a clinical laboratory test value(s) outside the range(s) specified in the protocol (or any other clinically significant laboratory abnormality), and the medical monitor had not provided written approval for study participation.

• The subject has 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 (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 has taken armodafinil, modafinil, or other stimulant medication for excessive sleepiness within 1 month of the screening visit.

• The patient is a pregnant or lactating woman.

• The patient is known to have tested positive for human immunodeficiency virus (HIV).

• The patient consumes an average of more than 600 mg of caffeine per day, including coffee, tea and/or other caffeine-containing beverages or food.

• The patient has used any investigational drug within 1 month before the screening visit.

• The patient is receiving workmen's compensation or was in active litigation with regard to TBI.

• The patient has a Self-Reported Hamilton Depression Rating Scale, 6 Item Version (S-HAM-D6) score of more than 4.

Exclusion Criteria (for Rollover Patients from Study C10953/3067/ES/MN):

• The patient has any clinically significant unstable or uncontrolled medical, surgical, or psychiatric conditions (treated or untreated) or may not be a suitable candidate for treatment with armodafinil, as judged by the investigator or medical monitor.

• The patient has current evidence of active psychosis, including stimulant-induced psychosis or mania.

• The patient has current evidence of non-medical substance use confirmed by results of a UDS.

• The patient has used any medications including OTC medicines disallowed by the protocol (except armodafinil use in study 3067) within 7 days or 5 half-lives of the drug and its active metabolites, whichever is longer.

• The patient has a clinically significant deviation from normal in the physical examination as judged by the investigator.

• The patient has a clinically significant laboratory abnormality, as judged by the investigator, without prior written approval by the medical monitor.

• The patient has hypersensitivity to armodafinil or modafinil, or any of the excipients of either.

• The patient is a pregnant or lactating woman.

• The patient is unlikely to comply with the study protocol, or is unsuitable for any other reason, as judged by the investigator.

• The patient consumes an average of more than 600 mg of caffeine per day (approximately equivalent to 5 or more cups of coffee), including coffee, tea, and/or other caffeine-containing beverages or food.

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 16	Hot Springs	Arkansas	United States	71913
4	Teva Investigational Site 5	Little Rock	Arkansas	United States	72205
5	Teva Investigational Site 44	Fountain Valley	California	United States	92708
6	Teva Investigational Site 49	La Palma	California	United States	90623
7	Teva Investigational Site 51	La Palma	California	United States	90623
8	Teva Investigational Site 55	San Diego	California	United States	92103
9	Teva Investigational Site 33	San Diego	California	United States	92161
10	Teva Investigational Site 53	Santa Monica	California	United States	90404
11	Teva Investigational Site 69	Wallingford	Connecticut	United States	06492
12	Teva Investigational Site 52	Hallandale Beach	Florida	United States	33009
13	Teva Investigational Site 47	Miami	Florida	United States	33173
14	Teva Investigational Site 1	Orlando	Florida	United States	32806
15	Teva Investigational Site 18	Pembroke Pines	Florida	United States	33026
16	Teva Investigational Site 38	Saint Petersburg	Florida	United States	33707
17	Teva Investigational Site 10	Spring Hill	Florida	United States	34609
18	Teva Investigational Site 17	Tampa	Florida	United States	33607
19	Teva Investigational Site 12	Atlanta	Georgia	United States	30342
20	Teva Investigational Site 14	Atlanta	Georgia	United States	30342
21	Teva Investigational Site 68	Gainesville	Georgia	United States	30501
22	Teva Investigational Site 67	Macon	Georgia	United States	31201
23	Teva Investigational Site 15	Suwanee	Georgia	United States	30024
24	Teva Investigational Site 46	Chicago	Illinois	United States	60675-6714
25	Teva Investigational Site 54	Chicago	Illinois	United States	60675-6714
26	Teva Investigational Site 59	Chicago	Illinois	United States	60675-6714
27	Teva Investigational Site 28	Danville	Indiana	United States	46122
28	Teva Investigational Site 19	Fort Wayne	Indiana	United States	46805
29	Teva Investigational Site 2	Indianapolis	Indiana	United States	46250
30	Teva Investigational Site 39	Indianapolis	Indiana	United States	46260
31	Teva Investigational Site 41	Iowa City	Iowa	United States	52242
32	Teva Investigational Site 9	Shawnee Mission	Kansas	United States	66201
33	Teva Investigational Site 48	Louisville	Kentucky	United States	40217
34	Teva Investigational Site 32	Chevy Chase	Maryland	United States	20815-6901
35	Teva Investigational Site 37	Belmont	Massachusetts	United States	02478
36	Teva Investigational Site 22	Saginaw	Michigan	United States	48604
37	Teva Investigational Site 7	Hattiesburg	Mississippi	United States	39402
38	Teva Investigational Site 42	Saint Louis	Missouri	United States	63143
39	Teva Investigational Site 56	Lincoln	Nebraska	United States	68510
40	Teva Investigational Site 63	New York	New York	United States	10019
41	Teva Investigational Site 36	West Seneca	New York	United States	14224
42	Teva Investigational Site 11	Durham	North Carolina	United States	27710
43	Teva Investigational Site 45	Winston-Salem	North Carolina	United States	27157
44	Teva Investigational Site 31	Cincinnati	Ohio	United States	45227
45	Teva Investigational Site 34	Cincinnati	Ohio	United States	45246
46	Teva Investigational Site 57	Middleburg Heights	Ohio	United States	44130
47	Teva Investigational Site 30	Toledo	Ohio	United States	43623
48	Teva Investigational Site 3	Oklahoma City	Oklahoma	United States	73112
49	Teva Investigational Site 64	Clarks Summit	Pennsylvania	United States	18411
50	Teva Investigational Site 13	Jefferson Hills	Pennsylvania	United States	15025
51	Teva Investigational Site 65	Columbia	South Carolina	United States	29201
52	Teva Investigational Site 61	Germantown	Tennessee	United States	38139
53	Teva Investigational Site 60	Austin	Texas	United States	78756
54	Teva Investigational Site 25	Dallas	Texas	United States	75235
55	Teva Investigational Site 8	Houston	Texas	United States	77030
56	Teva Investigational Site 20	Houston	Texas	United States	77063
57	Teva Investigational Site 23	San Antonio	Texas	United States	78229
58	Teva Investigational Site 35	Midvale	Utah	United States	84047
59	Teva Investigational Site 66	Midvale	Utah	United States	84047
60	Teva Investigational Site 24	Richmond	Virginia	United States	23249
61	Teva Investigational Site 50	West Allis	Wisconsin	United States	53227

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.

• Responsible Party: Cephalon, Inc.
• ClinicalTrials.gov Identifier: NCT00983437
• Other Study ID Numbers: C10953/3069/ES/MN
• First Posted: Sep 24, 2009
• Last Update Posted: Dec 17, 2021
• Last Verified: Dec 1, 2021

• Additional relevant MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Sleepiness; Wounds and Injuries; Modafinil

Study Results

Participant Flow

Recruitment Details	Of patients with excessive sleepiness associated with mild or moderate traumatic brain injury (TBI) who had completed study C10953/3067/ES/MN (NCT00893789) and were considered to be eligible for enrollment into the current study, 49 patients at 25 centers in the United States were enrolled. No new patients were screened for the study.
Pre-assignment Detail	Of 49 participants enrolled, 2 were withdrawn before taking any study drug for reasons of protocol violation and noncompliance with study procedures, respectively.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Period Title: Overall Study
STARTED	47
Safety Analysis Set (SAS)	47
Full Analysis Set (FAS)	45
COMPLETED	0
NOT COMPLETED	47

Baseline Characteristics

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Overall Participants	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.1 (10.15)
Sex: Female, Male (Count of Participants)
Female	19 38.8%
Male	30 61.2%
Race/Ethnicity, Customized (participants) [Number]
White	43 87.8%
Black	3 6.1%
Asian	2 4.1%
Other	1 2%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Discontinuations Due to AEs
Description	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).
Time Frame	Assessed from Screening through end of treatment; median (full range) of treatment was 98 (5.0 to 326.0) days.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (study participants who received at least 1 dose of study drug)

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	47
Any AE	29 59.2%
Severe AEs	0 0%
Treatment-related AEs	17 34.7%
Deaths	0 0%
SAEs (Other Than Deaths)	1 2%
Discontinuations (DCs) Due to AEs	7 14.3%
Protocol-defined AEs	3 6.1%
DCs due to AEs with onset during DB phase	2 4.1%

2. Primary Outcome

Title	Safety and Tolerability: Concomitant Medication Usage In Participants Throughout the Study
Description	Therapeutic classification of concomitant medications used by participants throughout the study. Participants are counted only once in each therapeutic class category.
Time Frame	Assessed from Screening through end of treatment; median (full range) of treatment was 98 (5.0 to 326.0) days.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	47
Participants receiving any concomitant medication	39 79.6%
All other therapeutic products	1 2%
Analgesics	10 20.4%
Anesthetics	1 2%
Anti-anemic preparations	1 2%
Antibacterials for systemic use	4 8.2%
Anti-emetics and antinauseants	1 2%
Antigout preparations	1 2%
Antihistamines for systemic use	4 8.2%
Anti-inflammatory and antirheumatic products	16 32.7%
Antimycotics for systemic use	1 2%
Antithrombotic agents	1 2%
Beta blocking agents	1 2%
Cardiac therapy	1 2%
Corticosteroids for systemic use	1 2%
Cough and cold preparations	2 4.1%
Drugs for acid-related disorders	3 6.1%
Drugs for obstructive airway diseases	3 6.1%
Drugs used in diabetes	1 2%
General nutrients	1 2%
Lipid-modifying agents	11 22.4%
Nasal preparations	4 8.2%
Other gynecologicals	2 4.1%
Psychoanaleptics	1 2%
Psycholeptics	2 4.1%
Sex hormones and modulators of the genital system	7 14.3%
Thyroid therapy	1 2%
Unspecified herbal	4 8.2%
Vitamins	12 24.5%

3. Primary Outcome

Title	Safety and Tolerability: Number of Participants With Clinically Significant Serum Chemistry Test Results
Description	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.
Time Frame	Assessed at Screening, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set who had a baseline and at least one post-baseline value.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	38
Participants with at least 1 abnormality (overall)	3 6.1%
Blood Urea Nitrogen >=10.71	2 4.1%
Uric Acid >=625 (male) or >=506 (female) µmol/L	1 2%

4. Primary Outcome

Title	Safety and Tolerability: Number of Participants With Clinically Significant Abnormal Vital Signs Measurements
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	47
Number [participants]	0 0%

5. Secondary Outcome

Title	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)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Full Analysis Set = participants in the Safety Analysis Set who had at least 1 post-baseline efficacy assessment; n=number of participants with value at baseline and given time point.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	45
Baseline (BL; n=45)	14.8 (2.60)
Change from BL at Week 2 (n=41)	-8.0 (4.42)
Change from BL at Month 1 (n=35)	-8.5 (4.37)
Change from BL at Month 2 (n=30)	-9.0 (3.56)
Change from BL at Month 3 (n=22)	-9.0 (3.53)
Change from BL at Month 6 (n=11)	-10.0 (3.26)
Change from BL at Month 9 (n=4)	-10.3 (4.79)
Change from BL at Endpoint (n=45)	-9.0 (4.48)

6. Secondary Outcome

Title	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)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Full Analysis Set = participants in the Safety Analysis Set who had at least 1 post-baseline efficacy assessment; n=number of participants with value at baseline and given time point.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	45
Baseline (BL; n=45)	4.4 (0.53)
Change from BL at Week 2 (n=41)	-1.9 (1.04)
Change from BL at Month 1 (n=35)	-2.1 (1.09)
Change from BL at Month 2 (n=30)	-2.6 (0.81)
Change from BL at Month 3 (n=22)	-2.4 (0.73)
Change from BL at Month 6 (n=11)	-2.5 (1.29)
Change from BL at Month 9 (n=4)	-3.3 (0.96)
Change from BL at Endpoint (n=45)	-2.2 (1.15)

7. Secondary Outcome

Title	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)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Full Analysis Set = participants in the Safety Analysis Set who had at least 1 post-baseline efficacy assessment; n=number of participants with value at baseline and given time point.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	45
Improved at Week 2 (n=41)	95 193.9%
Not Improved at Week 2 (n=41)	5 10.2%
Improved at Month 1 (n=35)	97 198%
Not Improved at Month 1 (n=35)	3 6.1%
Improved at Month 2 (n=30)	100 204.1%
Not Improved at Month 2 (n=30)	0 0%
Improved at Month 3 (n=22)	100 204.1%
Not Improved at Month 3 (n=22)	0 0%
Improved at Month 6 (n=11)	91 185.7%
Not Improved at Month 6 (n=11)	9 18.4%
Improved at Month 9 (n=4)	100 204.1%
Not Improved at Month 9 (n=4)	0 0%
Improved at Endpoint (n=45)	93 189.8%
Not Improved at Endpoint (n=45)	7 14.3%

8. Secondary Outcome

Title	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)
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 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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set (those in the Safety Analysis Set with at least 1 post-baseline efficacy assessment) with a TBI-WIS score at baseline; n=number of participants with value at baseline and given time point.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	34
Baseline (BL; n=34)	9.6 (6.93)
Change from BL at Month 3 (n=19)	-3.1 (5.87)
Change from BL at Month 6 (n=10)	-2.5 (7.32)
Change from BL at Month 9 (n=3)	-7.3 (2.52)
Change from BL at Endpoint (n=34)	-4.6 (6.52)

9. Primary Outcome

Title	Safety and Tolerability: Number of Participants With Clinically Significant Abnormal Hematology Test Results
Description	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.
Time Frame	Assessed at Screening, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	47
Number [participants]	0 0%

10. Primary Outcome

Title	Safety and Tolerability: Number of Participants With Clinically Significant Abnormal Urinalysis Results
Description	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.
Time Frame	Baseline, Months 6 and 12 (or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	47
Number [participants]	0 0%

11. Primary Outcome

Title	Safety and Tolerability: 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. 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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set; participants with a baseline and postbaseline value.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	45
Participants with at least 1 notable BP value	6 12.2%
Sitting systolic BP >=140 mm Hg + Increase >=10%	4 8.2%
Sitting diastolic BP >=90 mm Hg + Increase >=10%	3 6.1%

12. Primary Outcome

Title	Safety and Tolerability: 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. 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.
Time Frame	Baseline through Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set; only those participants with both baseline and endpoint ECG findings are summarized.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	35
Normal at BL → Normal Overall	17 34.7%
Normal at BL→ Abnormal Overall	4 8.2%
Abnormal at BL→ Normal Overall	3 6.1%
Abnormal at BL → Abnormal Overall	11 22.4%

13. Primary Outcome

Title	Safety and Tolerability: Physical Examination Findings Shifts From Baseline to Endpoint (Month 12 or Last Postbaseline Observation)
Description	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.
Time Frame	Baseline through Endpoint (Month 12 or last postbaseline observation); median (full range) of treatment was 98 (5.0 to 326.0) days.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set; only those participants with both baseline and endpoint physical examination findings are summarized.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	39
General Appearance: Normal at BL→Normal at EP	37 75.5%
General Appearance: Normal at BL→ Abnormal at EP	2 4.1%
General Appearance: Abnormal at BL→ Normal at EP	0 0%
General Appearance: Abnormal at BL→Abnormal at EP	0 0%
HEENT: Normal at BL→Normal at EP	37 75.5%
HEENT: Normal at BL→Abnormal at EP	1 2%
HEENT: Abnormal at BL→Normal at EP	1 2%
HEENT: Abnormal at BL→Abnormal at EP	0 0%
Chest/Lungs: Normal at BL→Normal at EP	39 79.6%
Chest/Lungs: Normal at BL→Abnormal at EP	0 0%
Chest/Lungs: Abnormal at BL→Normal at EP	0 0%
Chest/Lungs: Abnormal at BL→Abnormal at EP	0 0%
Heart: Normal at BL→Normal at EP	38 77.6%
Heart: Normal at BL→Abnormal at EP	1 2%
Heart: Abnormal at BL→Normal at EP	0 0%
Heart: Abnormal at BL→Abnormal at EP	0 0%
Abdomen: Normal at BL→Normal at EP	38 77.6%
Abdomen: Normal at BL→Abnormal at EP	1 2%
Abdomen: Abnormal at BL→Normal at EP	0 0%
Abdomen: Abnormal at BL→Abnormal at EP	0 0%
Musculoskeletal: Normal at BL→Normal at EP	38 77.6%
Musculoskeletal: Normal at BL→Abnormal at EP	1 2%
Musculoskeletal: Abnormal at BL→Normal at EP	0 0%
Musculoskeletal: Abnormal at BL→Abnormal at EP	0 0%
Skin: Normal at BL→Normal at EP	35 71.4%
Skin: Normal at BL→Abnormal at EP	0 0%
Skin: Abnormal at BL→Normal at EP	0 0%
Skin: Abnormal at BL→Abnormal at EP	4 8.2%
Lymph Nodes: Normal at BL→Normal at EP	34 69.4%
Lymph Nodes: Normal at BL→Abnormal at EP	0 0%
Lymph Nodes: Abnormal at BL→Normal at EP	1 2%
Lymph Nodes: Abnormal at BL→Abnormal at EP	0 0%
Neurological: Normal at BL→Normal at EP	37 75.5%
Neurological: Normal at BL→Abnormal at EP	1 2%
Neurological: Abnormal at BL→Normal at EP	1 2%
Neurological: Abnormal at BL→Abnormal at EP	0 0%

14. Primary Outcome

Title	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)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Safety Analysis Set; n=number of participants with nonmissing value at given time point.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	47
Week 2 (n=18), yes to any question	0 0%
Month 1 (n=18), yes to any question	0 0%
Month 2 (n=18), yes to any question	0 0%
Month 3 (n=13), yes to any question	0 0%
Month 6 (n=10), yes to any question	0 0%
Month 9 (n=4), yes to any question	0 0%
Endpoint (n=36), yes to 'Wish to Be Dead' question	1 2%
Endpoint (n=36), yes to all other questions	0 0%

15. Primary Outcome

Title	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)
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. 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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with a Baseline value; n=number of participants with baseline and postbaseline value at given time point.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	13
Baseline (BL; n=13)	1.4 (1.33)
Change from BL at Week 2 (n=13)	0.9 (3.43)
Change from BL at Month 1 (n=12)	0.2 (2.41)
Change from BL at Month 2 (n=9)	0.0 (2.35)
Change from BL at Month 3 (n=1)	-1.0 (NA)
Change from BL at Month 6 (n=0)	NA (NA)
Change from BL at Month 9 (n=0)	NA (NA)
Change from BL at Endpoint (n=13)	0.0 (2.65)

16. Secondary Outcome

Title	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)
Description	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.
Time Frame	Baseline, Months 3, 6, 9, and 12 (or last postbaseline observation)

Outcome Measure Data

Analysis Population Description

Changes from baseline in MOS-CF6 total score were not summarized. This assessment was not performed in study C10953/3067/ES/MN (NCT00893789); therefore, the data obtained at screening for the current study would represent true baseline data only for new participants, of which there were none.

Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
Measure Participants	0

Adverse Events

Time Frame	From Screening through end of treatment; median (full range) of treatment was 98 (5.0 to 326.0) days.
Arm/Group Title	Armodafinil
Arm/Group Description	Armodafinil tablets 150 mg or 250 mg administered orally, once daily in the morning.
All Cause Mortality
	Armodafinil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Armodafinil
	Affected / at Risk (%)	# Events
Total	1/47 (2.1%)
Psychiatric disorders
Psychotic Disorder	1/47 (2.1%)
Other (Not Including Serious) Adverse Events
	Armodafinil
	Affected / at Risk (%)	# Events
Total	29/47 (61.7%)
Gastrointestinal disorders
Nausea	3/47 (6.4%)
Dry mouth	2/47 (4.3%)
General disorders
Feeling jittery	2/47 (4.3%)
Infections and infestations
Upper respiratory tract infection	4/47 (8.5%)
Injury, poisoning and procedural complications
Muscle strain	2/47 (4.3%)
Investigations
Weight decreased	2/47 (4.3%)
Musculoskeletal and connective tissue disorders
Muscle tightness	2/47 (4.3%)
Pain in extremity	2/47 (4.3%)
Nervous system disorders
Headache	7/47 (14.9%)
Psychiatric disorders
Insomnia	3/47 (6.4%)
Anxiety	2/47 (4.3%)

Limitations/Caveats

The sponsor's decision to terminate the study early resulted in the small number of study participants, and related limitations to the interpretation of the study results.

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.