Trial Outcomes & Findings for Extension Study of the Safety and Efficacy of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder (NCT NCT01121536)

Last Updated: 2018-09-21

Results Overview

AEs were graded by the investigator for severity on a three-point scale: mild, moderate and severe. Causality is graded as either related or not related. A serious adverse event (SAE) is an AE resulting in death, a life-threatening adverse event, hospitalization, a persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may require medical intervention to prevent any of the previous results. Protocol-defined adverse events requiring expedited reporting included skin rash, hypersensitivity reaction, emergent suicidal ideation or suicide attempt, and psychosis.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

867 participants

Primary outcome timeframe

Day 1 up to Month 6

Results posted on

2018-09-21

Participant Flow

The final visit of the double-blind study (C10953/3071, /3072, or /3073; NCT01072929, 01072630, or 01305408) serves as the enrollment visit for this study.

Participant milestones

Participant milestones
Measure	Armodafinil 150-200 mg/Day Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Overall Study STARTED	867
Overall Study Safety Population	863
Overall Study Full Analysis Population	859
Overall Study COMPLETED	506
Overall Study NOT COMPLETED	361

Reasons for withdrawal

Reasons for withdrawal
Measure	Armodafinil 150-200 mg/Day Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Overall Study Adverse Event	63
Overall Study Lack of Efficacy	35
Overall Study Withdrawal by Subject	65
Overall Study Protocol Violation	20
Overall Study Noncompliance with study medication	12
Overall Study Noncompliance with study procedures	9
Overall Study Lost to Follow-up	39
Overall Study Other	118

Baseline Characteristics

Extension Study of the Safety and Efficacy of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Armodafinil 150-200 mg/Day n=867 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Age, Continuous	44.2 years STANDARD_DEVIATION 10.96 • n=5 Participants
Sex: Female, Male Female	525 Participants n=5 Participants
Sex: Female, Male Male	342 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	91 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	752 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	24 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	118 Participants n=5 Participants
Race (NIH/OMB) White	709 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	28 Participants n=5 Participants
Weight	83.7 kg STANDARD_DEVIATION 19.75 • n=5 Participants
Height	168.8 cm STANDARD_DEVIATION 9.54 • n=5 Participants
Body Mass Index	29.4 kg/m^2 STANDARD_DEVIATION 6.43 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to Month 6

Population: Safety population

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=863 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 adverse event	423 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Severe adverse event	26 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Treatment-related adverse event	219 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Deaths	0 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Other serious adverse events	27 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Withdrawn from study due to adverse events	57 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Protocol-defined adverse events	19 participants

PRIMARY outcome

Timeframe: Day 1 to Month 6

Population: Safety population with post-baseline serum chemistry assessments

Summary of serum chemistry tests in which at least one participant had a during study value that was clinically significant abnormal. The test name and criterion for clinically significant abnormal appear in each row. * ULN=upper limit of normal * BUN=Blood Urea Nitrogen; Uric acid has a normal range of 125-494 μmol/L. Criterion for clinically significant abnormal are different for men and women. * GGT = gamma-glutamyl transpeptidase with a normal range of 4-61 U/L * ALT = alanine aminotransferase with a normal range of 6-43 U/L * BUN = blood urea nitrogen with a normal range of 1.4-8.6 mmol/L * AST = aspartate aminotransferase with a normal range of 9-36 U/L

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=763 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Participants With Clinically Significant Abnormal Serum Chemistry Values >=1 clinical significant value	41 participants
Participants With Clinically Significant Abnormal Serum Chemistry Values Uric Acid, M>=625, F>=506 μmol/L	17 participants
Participants With Clinically Significant Abnormal Serum Chemistry Values GGT, >=3*ULN	16 participants
Participants With Clinically Significant Abnormal Serum Chemistry Values ALT, >=3*ULN	7 participants
Participants With Clinically Significant Abnormal Serum Chemistry Values BUN, >=10.71 mmol/L	7 participants
Participants With Clinically Significant Abnormal Serum Chemistry Values AST, >=3*ULN	3 participants

PRIMARY outcome

Timeframe: Day 1 to Month 6

Population: Safety population with post-baseline hematology assessments

Summary of hematology tests in which at least one participant had a during study value that was clinically significant abnormal. The test name and criterion for clinically significant abnormal appear in each row. * ULN=upper limit of normal * WBC - white blood cell counts with a normal range of 3.8-10.7 10\^9/L. * Hemoglobin with a normal range of 115-181 g/L * Hematocrit with a normal range of 0.34-0.54 L/L * Platelet counts with a normal range of 130-400 10\^9/L * ANC= absolute neutrophil counts with a normal range of 1.96-7.23 10\^9/L

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=757 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Participants With Clinically Significant Abnormal Hematology Values >=1 clinical significant value	13 participants
Participants With Clinically Significant Abnormal Hematology Values WBC, <=3*10^9/L	5 participants
Participants With Clinically Significant Abnormal Hematology Values Hemoglobin, M<=115, F<=95 g/L	4 participants
Participants With Clinically Significant Abnormal Hematology Values Hematocrit, M<0.37, F<0.32 L/L	8 participants
Participants With Clinically Significant Abnormal Hematology Values Platelets, <=75*10^9/L	1 participants
Participants With Clinically Significant Abnormal Hematology Values ANC, <=1*10^9/L	2 participants

PRIMARY outcome

Timeframe: Day 1 to Month 6

Population: Safety population with post-baseline urinalysis assessments

Summary of urinalysis tests in which at least one participant had a during study value that was clinically significant abnormal. Criterion for clinically significant abnormal urinalysis tests was \>=2 unit increase from baseline.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=761 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Participants With Clinically Significant Abnormal Urinalysis Values >=1 clinical significant value	28 participants
Participants With Clinically Significant Abnormal Urinalysis Values Urine hemoglobin	22 participants
Participants With Clinically Significant Abnormal Urinalysis Values Urine glucose	2 participants
Participants With Clinically Significant Abnormal Urinalysis Values Ketones	2 participants
Participants With Clinically Significant Abnormal Urinalysis Values Urine total protein	2 participants

PRIMARY outcome

Timeframe: Day 1 to Month 6

Population: Safety population with post-baseline vital signs assessments

Summary of vital signs tests in which at least one participant had a during study value that was clinically significant abnormal. Criterion for clinically significant abnormal vital signs are based on FDA Neuropharmacological Division criteria: * Pulse high: \>=120 beats per minute (bpm) and increase of \>=15 bpm from baseline * Pulse low: \<=50 bpm and decrease of \>=15 bpm from baseline * Sitting systolic blood pressure high: \>=180 mm Hg and increase of \>=20 mm Hg from baseline * Sitting systolic blood pressure low: \<=90 mm Hg and decrease of \>=20 mm Hg from baseline * Sitting diastolic blood pressure high: \>=105 mm Hg and increase of \>=15 mm Hg from baseline * Sitting diastolic blood pressure low: \<=50 mm Hg and decrease of \>=15 mm Hg from baseline

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=860 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Participants With Clinically Significant Abnormal Vital Signs Values >=1 clinical significant value	19 participants
Participants With Clinically Significant Abnormal Vital Signs Values Pulse high	2 participants
Participants With Clinically Significant Abnormal Vital Signs Values Pulse low	2 participants
Participants With Clinically Significant Abnormal Vital Signs Values Sitting systolic blood pressure high	3 participants
Participants With Clinically Significant Abnormal Vital Signs Values Sitting systolic blood pressure low	8 participants
Participants With Clinically Significant Abnormal Vital Signs Values Sitting diastolic blood pressure high	5 participants
Participants With Clinically Significant Abnormal Vital Signs Values Sitting diastolic blood pressure low	2 participants

PRIMARY outcome

Timeframe: Day 0 (baseline), Month 6 or last post-baseline observation

Population: Safety population of treated participants with both baseline and post-baseline ECG assessments

ECG was conducted at baseline which was before the first dose of study drug in the double-blind study, and at the month-6 visit of the open-label study (or early termination). RR= inter-beat intervals

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=759 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Endpoint in Electrocardiogram (ECG) Values PR interval	0.2 msec Standard Deviation 16.60
Change From Baseline to Endpoint in Electrocardiogram (ECG) Values QRS interval	0.0 msec Standard Deviation 7.03
Change From Baseline to Endpoint in Electrocardiogram (ECG) Values QT interval	1.4 msec Standard Deviation 25.66
Change From Baseline to Endpoint in Electrocardiogram (ECG) Values QTc interval Bazett	2.2 msec Standard Deviation 19.50
Change From Baseline to Endpoint in Electrocardiogram (ECG) Values QTc interval Fredericia	1.9 msec Standard Deviation 15.36
Change From Baseline to Endpoint in Electrocardiogram (ECG) Values RR interval	-2.2 msec Standard Deviation 137.98

PRIMARY outcome

Timeframe: Day 0 (baseline), Month 6 (or last post-baseline observation)

Population: Safety population of treated participants with baseline and endpoint assessments Participants n=: General appearance 785, HEENT 784, Chest and lungs 785, Heart 785, Abdomen 785, Musculoskeletal 785, Skin 785, Lymph nodes 780, Neurological 784

Baseline is the day prior to double-blind treatment. Assessments are summarized as normal or abnormal. The first assessment is the baseline assessment followed by the endpoint assessment. For example 'normal/abnormal' indicates participants who were normal at baseline and abnormal at endpoint. HEENT = Head, Eye, Ear, Nose and Throat exam

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=863 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Physical Examination Shifts From Baseline to Endpoint Lymph nodes: abnormal/normal	0 participants
Physical Examination Shifts From Baseline to Endpoint General appearance; normal/normal	714 participants
Physical Examination Shifts From Baseline to Endpoint General appearance; normal/abnormal	8 participants
Physical Examination Shifts From Baseline to Endpoint General appearance; abnormal/normal	23 participants
Physical Examination Shifts From Baseline to Endpoint General appearance; abnormal/abnormal	40 participants
Physical Examination Shifts From Baseline to Endpoint HEENT: normal/normal	753 participants
Physical Examination Shifts From Baseline to Endpoint HEENT: normal/abnormal	3 participants
Physical Examination Shifts From Baseline to Endpoint HEENT: abnormal/normal	15 participants
Physical Examination Shifts From Baseline to Endpoint HEENT: abnormal/abnormal	13 participants
Physical Examination Shifts From Baseline to Endpoint Chest+lungs: normal/normal	780 participants
Physical Examination Shifts From Baseline to Endpoint Chest+lungs: normal/abnormal	0 participants
Physical Examination Shifts From Baseline to Endpoint Chest+lungs: abnormal/normal	5 participants
Physical Examination Shifts From Baseline to Endpoint Chest+lungs: abnormal/abnormal	0 participants
Physical Examination Shifts From Baseline to Endpoint Heart: normal/normal	781 participants
Physical Examination Shifts From Baseline to Endpoint Heart: normal/abnormal	2 participants
Physical Examination Shifts From Baseline to Endpoint Heart: abnormal/normal	1 participants
Physical Examination Shifts From Baseline to Endpoint Heart: abnormal/abnormal	1 participants
Physical Examination Shifts From Baseline to Endpoint Abdomen: normal/normal	751 participants
Physical Examination Shifts From Baseline to Endpoint Abdomen: normal/abnormal	5 participants
Physical Examination Shifts From Baseline to Endpoint Abdomen: abnormal/normal	16 participants
Physical Examination Shifts From Baseline to Endpoint Abdomen: abnormal/abnormal	13 participants
Physical Examination Shifts From Baseline to Endpoint Musculoskeletal: normal/normal	756 participants
Physical Examination Shifts From Baseline to Endpoint Musculoskeletal: normal/abnormal	7 participants
Physical Examination Shifts From Baseline to Endpoint Musculoskeletal: abnormal/normal	11 participants
Physical Examination Shifts From Baseline to Endpoint Musculoskeletal: abnormal/abnormal	11 participants
Physical Examination Shifts From Baseline to Endpoint Skin: normal/normal	707 participants
Physical Examination Shifts From Baseline to Endpoint Skin: normal/abnormal	9 participants
Physical Examination Shifts From Baseline to Endpoint Skin: abnormal/normal	41 participants
Physical Examination Shifts From Baseline to Endpoint Skin: abnormal/abnormal	28 participants
Physical Examination Shifts From Baseline to Endpoint Lymph nodes: normal/normal	779 participants
Physical Examination Shifts From Baseline to Endpoint Lymph nodes: normal/abnormal	0 participants
Physical Examination Shifts From Baseline to Endpoint Lymph nodes: abnormal/abnormal	1 participants
Physical Examination Shifts From Baseline to Endpoint Neurological: normal/normal	777 participants
Physical Examination Shifts From Baseline to Endpoint Neurological: normal/abnormal	2 participants
Physical Examination Shifts From Baseline to Endpoint Neurological: abnormal/normal	2 participants
Physical Examination Shifts From Baseline to Endpoint Neurological: abnormal/abnormal	3 participants

PRIMARY outcome

Timeframe: Day 0 (baseline), Month 6 (or last post-baseline observation)

Population: Safety population of treated participants with both baseline and post-baseline assessments.

Baseline was the score before the first dose of study drug in the double-blind study.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=788 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Endpoint in Body Weight	-0.8 kg Standard Deviation 5.67

PRIMARY outcome

Timeframe: Day 0 (baseline), Month 6 or last post-baseline observation

Population: The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with both baseline (double-blind study) and treatment assessments during the open-label study.

The YMRS is a clinician-rated, 11-item checklist used to measure the severity of manic episodes. Information for assigning scores is gained from the participant's subjective reported symptoms over the previous 48 hours and from clinical observation during the interview. Seven items are ranked 0 through 4 and have descriptors associated with each severity level. Four items (irritability, speech, content, and disruptive-aggressive behavior) are scored 0 through 8 and have descriptors for every second increment. The total scale is 0-60. A score of ≤12 indicates remission of manic symptoms, and higher scores indicate greater severity of mania. Negative change from baseline scores indicate a decrease in severity of mania. Baseline was the score before the first dose of study drug in the double-blind study.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=858 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score	-0.7 units on a scale Standard Deviation 4.28

PRIMARY outcome

Timeframe: Day 1, Week 1, Months 1, 2, 4 and 6 or last post-baseline visit

Population: Safety population; only 19 participants were asked the last three questions as the inclusion of these questions depends on physician assessment.

The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The number of participants who had findings on any of the C-SSRS-SLV (SLV=since last visit) categories at any of the time frames are indicated. \- C-SSRS=Columbia Suicide Severity Rating Scale

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=863 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Suicidal behavior - Actual attempt	1 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Non-suicidal self-injurious behaviour	1 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Suicidal behavior - Interrupted attempt	0 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Suicidal behavior - Aborted attempt	0 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Suicidal behavior - suicidal behavior	0 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Suicidal behavior - Preparatory acts/behavior	1 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Suicidal behavior - Completed suicide	0 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Suicidal ideation - Wish to be dead	15 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Non-specific active suicidal thoughts	4 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Any methods (not plan) w/o intent to act	2 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Some intent to act, w/o specific plan	1 participants
Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) Suicidal ideation - Specific plan and intent	1 participants

PRIMARY outcome

Timeframe: Day 0 (baseline), Month 6 (or last post-baseline observation)

Population: Safety population of treated participants with both a baseline and post-baseline assessment.

The ISI is a participant-rated, 7-item questionnaire designed to assess the severity of the participant's insomnia. Each item is ranked 0 (none) through 4 (very severe) and has a descriptor associated with each severity level. Total range is 0 (no insomnia) to 28 (very severe insomnia). Responses to each item are added to obtain a total score to determine the severity of insomnia. Negative change from baseline scores indicate a decrease in severity of insomnia. Baseline was the assessment before the first dose of study drug in the double-blind study.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=855 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score	-9.1 units on a scale Standard Deviation 7.66

PRIMARY outcome

Timeframe: Day 0 (baseline), Month 6 or last post-baseline observation

Population: Safety population of participants with both a baseline and post-baseline assessment.

HAM-A measures the severity of anxiety symptoms. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Negative change from baseline scores indicate a decrease in severity of anxiety. Baseline was the score before the first dose of study drug in the double-blind study.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=786 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score	-6.2 units on a scale Standard Deviation 5.68

SECONDARY outcome

Timeframe: Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

Population: Full analysis set

The IDS-C30 is a standardized 30-item, clinician-rated scale to assess the severity of a participant's depressive symptoms. Every effort was made to have the same rater evaluate a participant across all visits. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression. Baseline was the score before the first dose of study drug in the double-blind study.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=859 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Week 1 (837)	-23.7 units on a scale Standard Deviation 12.10
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Month 1 (793)	-25.8 units on a scale Standard Deviation 11.61
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Month 2 (716)	-27.6 units on a scale Standard Deviation 11.38
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Month 4 (578)	-29.2 units on a scale Standard Deviation 11.68
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Month 6 (503)	-29.7 units on a scale Standard Deviation 12.06
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Endpoint (857)	-27.5 units on a scale Standard Deviation 13.08

SECONDARY outcome

Timeframe: Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

Population: Full analysis set

The QIDS-C16 was derived from specified items in the IDS-C30, clinician-rated scale to assess the severity of a participant's depressive symptoms. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression. Baseline was the score before the first dose of study drug in the double-blind study.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=859 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Week 1 (838)	-9.3 units on a scale Standard Deviation 4.68
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Month 1 (793)	-10.0 units on a scale Standard Deviation 4.47
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Month 2 (716)	-10.6 units on a scale Standard Deviation 4.52
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Month 4 (578)	-11.1 units on a scale Standard Deviation 4.70
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Month 6 (503)	-11.3 units on a scale Standard Deviation 4.69
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Endpoint (857)	-10.6 units on a scale Standard Deviation 5.07

SECONDARY outcome

Timeframe: Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

Population: Full analysis set

The CGI-S is an observer-rated scale that measures illness severity on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). Negative change from baseline values indicate improvement in the severity of depression. Baseline was the score before the first dose of study drug in the double-blind study.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=859 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression Week 1 (838)	-1.7 units on a scale Standard Deviation 1.17
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression Month 1 (791)	-1.9 units on a scale Standard Deviation 1.17
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression Month 2 (716)	-2.0 units on a scale Standard Deviation 1.18
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression Month 4 (578)	-2.2 units on a scale Standard Deviation 1.16
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression Month 6 (502)	-2.3 units on a scale Standard Deviation 1.18
Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression Endpoint (859)	-2.0 units on a scale Standard Deviation 1.31

SECONDARY outcome

Timeframe: Day 0 (baseline), Month 6 or the last post-baseline assessment)

Population: Full analysis set of participants with both a baseline and post-baseline assessment.

The Global Assessment of Functioning (GAF) is a numeric scale (1 through 100) used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of adults, e.g., how well or adaptively one is meeting various problems-in-living. Ratings of 1 - 10 mean the participant is in persistent danger of severely hurting self or others (e.g., recurrent violence) or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death. Ratings of 91 - 100 indicate no symptoms, and the participant exhibits superior functioning in a wide range of activities, life's problems never seem to get out of hand, is sought out by others because of his or her many positive qualities. Positive change from baseline values indicate improvement in functioning. Baseline was the score before the first dose of study drug in the double-blind study.

Outcome measures

Outcome measures
Measure	Armodafinil 150-200 mg/Day n=779 Participants Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Change From Baseline to Endpoint in the Global Assessment for Functioning (GAF) Scale	17.7 units on a scale Standard Deviation 13.61

Adverse Events

Armodafinil 150-200 mg/Day

Serious events: 27 serious events

Other events: 133 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Armodafinil 150-200 mg/Day n=863 participants at risk Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Cardiac disorders Angina pectoris	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Cardiac disorders Myocardial infarction	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Cardiac disorders Torsade de pointes	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Gastrointestinal disorders Colitis	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Gastrointestinal disorders Diarrhoea	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Hepatobiliary disorders Cholecystitis acute	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Infections and infestations Laryngitis	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Infections and infestations Pilonidal cyst	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Infections and infestations Sialoadenitis	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Injury, poisoning and procedural complications Accidental overdose	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Metabolism and nutrition disorders Dehydration	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Nervous system disorders Transient ischaemic attack	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Psychiatric disorders Acute psychosis	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Psychiatric disorders Agitation	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Psychiatric disorders Alcohol abuse	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Psychiatric disorders Alcohol withdrawal syndrome	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Psychiatric disorders Bipolar I disorder	0.35% 3/863 • Number of events 3 • Day 1 up to 6 months
Psychiatric disorders Homicidal ideation	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Psychiatric disorders Major depression	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Psychiatric disorders Mania	0.58% 5/863 • Number of events 6 • Day 1 up to 6 months
Psychiatric disorders Suicidal ideation	0.35% 3/863 • Number of events 3 • Day 1 up to 6 months
Psychiatric disorders Suicide attempt	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Vascular disorders Deep vein thrombosis	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months
Vascular disorders Hypotension	0.12% 1/863 • Number of events 1 • Day 1 up to 6 months

Other adverse events

Other adverse events
Measure	Armodafinil 150-200 mg/Day n=863 participants at risk Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Nervous system disorders Headache	11.1% 96/863 • Number of events 119 • Day 1 up to 6 months
Psychiatric disorders Insomnia	5.7% 49/863 • Number of events 56 • Day 1 up to 6 months

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 215-591-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER