Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder (NCT NCT01072929)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

433 participants

Primary outcome timeframe

Day 0 (baseline), Week 8

Results posted on

2016-04-27

Participant Flow

Four geographic regions that include countries with similar clinical practices. * Region 1: USA and Canada * Region 2: Bulgaria, Ukraine, Poland, and Serbia * Region 3: Australia, France, and Spain * Region 4: Argentina

Participants were randomized (1:1) to receive150 mg/day armodafinil or matching placebo. The 200-mg/day armodafinil treatment group was discontinued per protocol Amendment 03. Randomization was stratified on the basis of the mood-stabilizing medication and region of the world.

Participant milestones

Participant milestones
Measure	Placebo Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	Armodafinil 200 mg/Day Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
Overall Study STARTED	199	201	33
Overall Study Safety Population	199	198	32
Overall Study Full Analysis Population	196	197	31
Overall Study COMPLETED	155	150	24
Overall Study NOT COMPLETED	44	51	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	Armodafinil 200 mg/Day Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
Overall Study Adverse Event	8	11	2
Overall Study Lack of Efficacy	7	4	0
Overall Study Withdrawal by Subject	7	15	3
Overall Study Protocol Violation	13	11	2
Overall Study Lost to Follow-up	8	4	1
Overall Study Noncompliance with study medication	0	3	0
Overall Study Noncompliance with study procedures	1	0	1
Overall Study Other	0	3	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety 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	Placebo n=199 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=201 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	Armodafinil 200 mg/Day n=33 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.	Total n=433 Participants Total of all reporting groups
Age, Continuous	42.6 years STANDARD_DEVIATION 10.47 • n=5 Participants	44.0 years STANDARD_DEVIATION 11.34 • n=7 Participants	44.8 years STANDARD_DEVIATION 11.78 • n=5 Participants	43.4 years STANDARD_DEVIATION 10.99 • n=4 Participants
Sex: Female, Male Female	129 Participants n=5 Participants	133 Participants n=7 Participants	26 Participants n=5 Participants	288 Participants n=4 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	68 Participants n=7 Participants	7 Participants n=5 Participants	145 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=5 Participants	32 Participants n=7 Participants	1 Participants n=5 Participants	61 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	166 Participants n=5 Participants	167 Participants n=7 Participants	32 Participants n=5 Participants	365 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	29 Participants n=5 Participants	17 Participants n=7 Participants	4 Participants n=5 Participants	50 Participants n=4 Participants
Race (NIH/OMB) White	163 Participants n=5 Participants	179 Participants n=7 Participants	27 Participants n=5 Participants	369 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Weight	83.9 kg STANDARD_DEVIATION 22.78 • n=5 Participants	83.1 kg STANDARD_DEVIATION 20.65 • n=7 Participants	87.3 kg STANDARD_DEVIATION 20.46 • n=5 Participants	83.8 kg STANDARD_DEVIATION 21.53 • n=4 Participants
Height	168.4 cm STANDARD_DEVIATION 10.56 • n=5 Participants	167.2 cm STANDARD_DEVIATION 9.32 • n=7 Participants	167.2 cm STANDARD_DEVIATION 7.57 • n=5 Participants	167.8 cm STANDARD_DEVIATION 9.80 • n=4 Participants
Body Mass Index	29.5 kg/m^2 STANDARD_DEVIATION 7.04 • n=5 Participants	29.7 kg/m^2 STANDARD_DEVIATION 6.91 • n=7 Participants	31.3 kg/m^2 STANDARD_DEVIATION 6.56 • n=5 Participants	29.7 kg/m^2 STANDARD_DEVIATION 6.94 • n=4 Participants
Time Since Start of Current Depressive Episode	13.7 weeks STANDARD_DEVIATION 10.69 • n=5 Participants	12.9 weeks STANDARD_DEVIATION 9.38 • n=7 Participants	15.2 weeks STANDARD_DEVIATION 10.42 • n=5 Participants	13.4 weeks STANDARD_DEVIATION 10.07 • n=4 Participants
Time Since First Diagnosis for Bipolar	10.9 years STANDARD_DEVIATION 8.51 • n=5 Participants	10.6 years STANDARD_DEVIATION 8.55 • n=7 Participants	13.7 years STANDARD_DEVIATION 10.23 • n=5 Participants	11.0 years STANDARD_DEVIATION 8.69 • n=4 Participants

PRIMARY outcome

Timeframe: Day 0 (baseline), Week 8

Population: Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment.

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.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=197 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=228 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)	-17.9 units on a scale Standard Error 1.10	-21.7 units on a scale Standard Error 1.11	-20.8 units on a scale Standard Error 1.07

SECONDARY outcome

Timeframe: Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Population: Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The denominator for calculating the percentages at each visit is the number of participants with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.

A responder is a participant with a ≥50% decrease or greater from baseline in the total score of the IDS-C30. 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.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=197 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=31 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 4 (178, 168, 27)	23 percentage of participants	26 percentage of participants	37 percentage of participants
Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 6 (160, 158, 21)	38 percentage of participants	39 percentage of participants	43 percentage of participants
Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 1 (191, 193, 29)	4 percentage of participants	6 percentage of participants	10 percentage of participants
Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 2 (188, 181, 27)	12 percentage of participants	8 percentage of participants	26 percentage of participants
Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 8 (155, 150, 24)	39 percentage of participants	55 percentage of participants	42 percentage of participants
Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 7 (152, 144, 19)	39 percentage of participants	51 percentage of participants	47 percentage of participants
Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Endpoint (196, 197, 31)	34 percentage of participants	46 percentage of participants	39 percentage of participants

SECONDARY outcome

Timeframe: Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Population: Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The denominator for calculating the percentages at each visit is the number of participants with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.

A participant in remission was defined as a participant with an IDS-C30 total score of 11 or less. 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.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=197 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=31 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 2 (188, 181, 27)	2 percentage of participants	2 percentage of participants	7 percentage of participants
Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 4 (178, 168, 27)	6 percentage of participants	4 percentage of participants	11 percentage of participants
Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 6 (160, 158, 21)	16 percentage of participants	15 percentage of participants	10 percentage of participants
Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 7 (152, 144, 19)	22 percentage of participants	17 percentage of participants	16 percentage of participants
Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 8 (155, 150, 24)	22 percentage of participants	28 percentage of participants	17 percentage of participants
Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Endpoint (196, 197, 31)	17 percentage of participants	21 percentage of participants	13 percentage of participants
Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score Week 1 (191, 193, 29)	1 percentage of participants	1 percentage of participants	3 percentage of participants

SECONDARY outcome

Timeframe: Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Population: Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. Participants are included in the analysis at each timepoint if they have a nonmissing value at that visit. Endpoint for analyses was the last observed postbaseline data.

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.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=197 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=31 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Week 1 (191, 193, 29)	-6.1 units on a scale Standard Deviation 7.46	-6.5 units on a scale Standard Deviation 7.90	-9.8 units on a scale Standard Deviation 8.96
Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Week 2 (188, 181, 27)	-10.2 units on a scale Standard Deviation 8.60	-10.4 units on a scale Standard Deviation 9.08	-12.9 units on a scale Standard Deviation 10.92
Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Week 4 (178, 168, 27)	-14.3 units on a scale Standard Deviation 11.04	-15.6 units on a scale Standard Deviation 10.33	-15.3 units on a scale Standard Deviation 13.09
Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Week 6 (160, 158, 21)	-18.3 units on a scale Standard Deviation 12.23	-19.7 units on a scale Standard Deviation 10.49	-17.4 units on a scale Standard Deviation 13.42
Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Week 7 (152, 144, 19)	-18.8 units on a scale Standard Deviation 13.27	-21.7 units on a scale Standard Deviation 11.30	-17.8 units on a scale Standard Deviation 14.57
Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Week 8 (155, 150, 24)	-19.7 units on a scale Standard Deviation 13.19	-23.3 units on a scale Standard Deviation 12.22	-17.0 units on a scale Standard Deviation 14.64
Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) Endpoint (196, 197, 31)	-17.3 units on a scale Standard Deviation 14.06	-20.2 units on a scale Standard Deviation 13.44	-15.8 units on a scale Standard Deviation 13.55

SECONDARY outcome

Timeframe: Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Population: Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The number of participants at each visit are those with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.

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.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=197 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=31 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Week 1 (191, 194, 29)	-2.3 units on a scale Standard Deviation 3.05	-2.8 units on a scale Standard Deviation 3.53	-4.1 units on a scale Standard Deviation 3.95
Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Week 2 (188, 181, 27)	-3.8 units on a scale Standard Deviation 3.66	-4.4 units on a scale Standard Deviation 3.83	-5.0 units on a scale Standard Deviation 4.80
Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Week 7 (152, 145, 19)	-7.2 units on a scale Standard Deviation 5.32	-8.6 units on a scale Standard Deviation 4.16	-7.6 units on a scale Standard Deviation 6.36
Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Endpoint (196, 197, 31)	-6.6 units on a scale Standard Deviation 5.63	-8.0 units on a scale Standard Deviation 5.23	-6.6 units on a scale Standard Deviation 5.40
Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Week 4 (178, 168, 27)	-5.6 units on a scale Standard Deviation 4.55	-6.5 units on a scale Standard Deviation 4.23	-6.4 units on a scale Standard Deviation 4.96
Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Week 6 (160, 158, 21)	-6.9 units on a scale Standard Deviation 5.01	-8.1 units on a scale Standard Deviation 3.91	-7.4 units on a scale Standard Deviation 5.22
Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) Week 8 (155, 150, 24)	-7.6 units on a scale Standard Deviation 5.39	-9.4 units on a scale Standard Deviation 4.56	-7.3 units on a scale Standard Deviation 5.56

SECONDARY outcome

Timeframe: Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Population: Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The number of participants is those with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.

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.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=197 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=31 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression Week 8 (155, 150, 24)	-1.5 units on a scale Standard Deviation 1.27	-1.7 units on a scale Standard Deviation 1.17	-1.3 units on a scale Standard Deviation 1.49
Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression Week 2 (188, 181, 28)	-0.5 units on a scale Standard Deviation 0.68	-0.6 units on a scale Standard Deviation 0.80	-0.5 units on a scale Standard Deviation 0.79
Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression Week 1 (191, 194, 29)	-0.3 units on a scale Standard Deviation 0.54	-0.4 units on a scale Standard Deviation 0.72	-0.5 units on a scale Standard Deviation 0.74
Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression Week 4 (178, 168, 27)	-0.9 units on a scale Standard Deviation 0.93	-0.9 units on a scale Standard Deviation 0.94	-0.8 units on a scale Standard Deviation 0.97
Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression Week 6 (160, 158, 21)	-1.2 units on a scale Standard Deviation 1.10	-1.4 units on a scale Standard Deviation 1.01	-0.9 units on a scale Standard Deviation 1.14
Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression Week 7 (152, 145, 19)	-1.3 units on a scale Standard Deviation 1.20	-1.6 units on a scale Standard Deviation 1.10	-1.1 units on a scale Standard Deviation 1.33
Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression Endpoint (196, 197, 31)	-1.3 units on a scale Standard Deviation 1.28	-1.4 units on a scale Standard Deviation 1.26	-1.2 units on a scale Standard Deviation 1.39

SECONDARY outcome

Timeframe: Day 0 (baseline), Weeks 4, 8, and last postbaseline observation (up to 8 weeks)

Population: Full analysis set which includes participants who took 1 or more doses of study drug and who have at least 1 postbaseline IDS-C30 efficacy assessment. The number of participants is those with a nonmissing value at that visit. Endpoint was the last observed postbaseline data.

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.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=197 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=31 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale Week 4 (175, 168, 27)	7.2 units on a scale Standard Deviation 9.24	7.7 units on a scale Standard Deviation 9.78	8.9 units on a scale Standard Deviation 8.74
Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale Week 8 (153, 150, 24)	11.4 units on a scale Standard Deviation 13.67	15.6 units on a scale Standard Deviation 13.37	13.6 units on a scale Standard Deviation 15.04
Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale Endpoint (191, 189, 29)	10.2 units on a scale Standard Deviation 13.31	12.8 units on a scale Standard Deviation 13.42	12.2 units on a scale Standard Deviation 14.11

SECONDARY outcome

Timeframe: Day 1 to Week 9

Population: The safety analysis set includes randomized participants who took 1 or more doses of study drug.

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.

Outcome measures

Outcome measures
Measure	Placebo n=199 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=198 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=32 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Participants With Treatment-Emergent Adverse Events (TEAE) Severe adverse event	8 participants	6 participants	4 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Other serious adverse events	5 participants	3 participants	2 participants
Participants With Treatment-Emergent Adverse Events (TEAE) >=1 adverse event	91 participants	95 participants	23 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Treatment-related adverse event	44 participants	44 participants	13 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Deaths	0 participants	0 participants	1 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Withdrawn from study due to adverse events	7 participants	11 participants	2 participants
Participants With Treatment-Emergent Adverse Events (TEAE) Protocol-defined adverse events	4 participants	7 participants	0 participants

SECONDARY outcome

Timeframe: Day 0 (baseline), last postbaseline observation (up to 8 weeks)

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 and during treatment assessments.

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.

Outcome measures

Outcome measures
Measure	Placebo n=197 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=198 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=31 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score	-1.1 units on a scale Standard Deviation 3.37	-1.1 units on a scale Standard Deviation 3.13	-1.0 units on a scale Standard Deviation 2.39

SECONDARY outcome

Timeframe: Day 0 (baseline), last postbaseline observation (up to 8 weeks)

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 and during treatment assessments.

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.

Outcome measures

Outcome measures
Measure	Placebo n=193 Participants Participants were administered placebo and titrated to match the armodafinil treatment arms. Total treatment was 8 weeks.	Armodafinil 150 mg/Day n=192 Participants Participants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 150 mg/day. The 150 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment.	All Armodafinil n=30 Participants This arm combines participants who took 150 mg/day and those in the discontinued treatment arm who took 200 mg/day of armodafinil for 8 weeks.
Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score	-4.2 units on a scale Standard Deviation 4.69	-4.2 units on a scale Standard Deviation 5.88	-3.3 units on a scale Standard Deviation 4.31

SECONDARY outcome

Timeframe: Day 0 (baseline), last postbaseline observation (up to 8 weeks)

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 and during treatment assessments.

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.