Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
42 centers in the US, Romania, Bulgaria, and Hungary. First participant enrolled: June 2007/ Last participant last visit: December 2008

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study consisted of a 1 to 2 week screening period, an 8 week double blind treatment period, and a 1 week follow up period.

Reporting Groups

	Description
Armodafinil 150 mg/Day	Armodafinil was titrated up to the target dosage of 150 mg/day (daily dose was administered each morning). Patients began taking blinded armodafinil at a dose of 50 mg/day (1 tablet) on the day following the baseline visit. Doses were increased by 50 mg/day (1 tablet) to a dose of 100 mg/day on Day 2 and 3, and then again by 50 mg /day on day 4 for a target dose of 150 mg/day. Following titration, patients continued taking 150 mg/day of armodafinil for the duration of the study. If a patient was unable to tolerate (recurrent or persistent adverse events) the study drug, 1 reduction in dosage (ie, minimum dosage 100 mg/day [2 tablets]) was allowed. The dosage could not be increased after it was decreased.
Placebo	Placebo tablets matching the 50 mg armodafinil tablet were used in a manner identical to that of the armodafinil tablets. Study drug was titrated up to the target dosage of 3 tablets / day (daily dose was administered each morning). Patients began taking blinded study drug at a dose of 1 tablet daily on the day following the baseline visit. Doses were increased by 1 tablet to a dose of 2 tablets/day on Day 2 and 3, and then again by 1 tablet /day on day 4 for a target dose of 3 tablets/day. Following titration, patients continued taking 3 tablets/day of study drug for the duration of the study. If a patient was unable to tolerate (recurrent or persistent adverse events) the study drug, 1 reduction in dosage (ie, minimum dosage 2 tablets/day) was allowed. The dosage could not be increased after it was decreased.

Participant Flow:   Overall Study

	Armodafinil 150 mg/Day	Placebo
STARTED	128 [1]	129 [2]
COMPLETED	89	90
NOT COMPLETED	39	39
Adverse Event	16	11
Lack of Efficacy	1	3
Lost to Follow-up	4	6
Physician Decision	3	1
Protocol Violation	10	7
Withdrawal by Subject	3	9
Miscellaneous	2	2

Reporting Groups

	Description
Armodafinil 150 mg/Day	Armodafinil was titrated up to the target dosage of 150 mg/day (daily dose was administered each morning). Patients began taking blinded armodafinil at a dose of 50 mg/day (1 tablet) on the day following the baseline visit. Doses were increased by 50 mg/day (1 tablet) to a dose of 100 mg/day on Day 2 and 3, and then again by 50 mg /day on day 4 for a target dose of 150 mg/day. Following titration, patients continued taking 150 mg/day of armodafinil for the duration of the study. If a patient was unable to tolerate (recurrent or persistent adverse events) the study drug, 1 reduction in dosage (ie, minimum dosage 100 mg/day [2 tablets]) was allowed. The dosage could not be increased after it was decreased.
Placebo	Placebo tablets matching the 50 mg armodafinil tablet were used in a manner identical to that of the armodafinil tablets. Study drug was titrated up to the target dosage of 3 tablets / day (daily dose was administered each morning). Patients began taking blinded study drug at a dose of 1 tablet daily on the day following the baseline visit. Doses were increased by 1 tablet to a dose of 2 tablets/day on Day 2 and 3, and then again by 1 tablet /day on day 4 for a target dose of 3 tablets/day. Following titration, patients continued taking 3 tablets/day of study drug for the duration of the study. If a patient was unable to tolerate (recurrent or persistent adverse events) the study drug, 1 reduction in dosage (ie, minimum dosage 2 tablets/day) was allowed. The dosage could not be increased after it was decreased.

Baseline Measures

	Armodafinil 150 mg/Day	Placebo	Total
Number of Participants   [units: participants]	128	129	257
Age   [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	128	129	257
>=65 years	0	0	0
Age   [units: years] Mean ± Standard Deviation	42.6  ± 11.34	44.9  ± 11.53	43.7  ± 11.47
Gender   [units: participants]
Female	64	76	140
Male	64	53	117
Region of Enrollment   [units: participants]
United States	115	105	220
Hungary	0	2	2
Romania	5	7	12
Bulgaria	8	15	23

1.  Primary:

The Mean Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30)   [ Time Frame: Baseline and 8 weeks from start of study drug administration (or last observation after baseline) ]

2.  Secondary:

The Mean Change From Baseline to Week 1 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30)   [ Time Frame: Baseline and 1 week following the start of study drug administration ]

3.  Secondary:

The Mean Change From Baseline to Week 2 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30)   [ Time Frame: Baseline and 2 weeks following the start of study drug administration ]

4.  Secondary:

The Mean Change From Baseline to Week 3 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30)   [ Time Frame: Baseline and 3 weeks following the start of study drug administration ]

5.  Secondary:

The Mean Change From Baseline to Week 4 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30)   [ Time Frame: Baseline and 4 weeks following the start of study drug administration ]

6.  Secondary:

The Mean Change From Baseline to Week 6 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30)   [ Time Frame: Baseline and 6 weeks following the start of study drug administration ]

7.  Secondary:

The Mean Change From Baseline to Week 8 in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30)   [ Time Frame: Baseline and 8 weeks following the start of study drug administration ]

8.  Secondary:

Number of Patients Achieving Remission at Endpoint According to the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)   [ Time Frame: Baseline, 4 and 8 weeks following start of study drug administration (or last observation after baseline) ]

9.  Secondary:

Number of Patients Achieving "Response" at Endpoint According to the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)   [ Time Frame: Baseline, 4 and 8 weeks following start of study drug administration (or last observation after baseline) ]

10.  Secondary:

Number of Patients Achieving "Sustained Remission" at Endpoint According to the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)   [ Time Frame: Baseline, 4 and 8 weeks following start of study drug administration (or last observation after baseline) ]

11.  Secondary:

Number of Patients Achieving "Sustained Response" at Endpoint According to the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)   [ Time Frame: Baseline, 4 and 8 weeks following start of study drug administration (or last observation after baseline) ]

12.  Secondary:

Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) Combination of Items 1-3   [ Time Frame: Baseline and 8 weeks (or last observation after baseline) ]

13.  Secondary:

Change From Baseline to Week 4 on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) Combination of Items 1-3   [ Time Frame: Baseline and 4 weeks following the start of study drug administration ]

14.  Secondary:

Change From Baseline to Week 8 on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) Combination of Items 1-3   [ Time Frame: Baseline and 8 weeks following the start of study drug administration ]

15.  Secondary:

Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) - Item 4   [ Time Frame: Baseline and 8 weeks (or last observation after baseline) ]

16.  Secondary:

Change From Baseline to Week 4 on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) - Item 4   [ Time Frame: Baseline and 4 weeks following the start of study drug administration ]

17.  Secondary:

Change From Baseline to Week 8 on 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30) - Item 4   [ Time Frame: Baseline and 8 weeks following the start of study drug administration ]

18.  Secondary:

Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score   [ Time Frame: Baseline and Endpoint (8 weeks following the start of study drug administration or last observation after baseline) ]

19.  Secondary:

Change From Baseline to Week 4 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score   [ Time Frame: Baseline and 4 weeks following the start of study drug administration ]

20.  Secondary:

Change From Baseline to Week 8 in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score   [ Time Frame: Baseline and 8 weeks following the start of study drug administration ]

21.  Secondary:

Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16)   [ Time Frame: Baseline and 8 weeks (or last observation after baseline) ]

22.  Secondary:

Change From Baseline to Week 1 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16)   [ Time Frame: Baseline and 1 week following the start of study drug administration ]

23.  Secondary:

Change From Baseline to Week 2 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16)   [ Time Frame: Baseline and 2 weeks following the start of study drug administration ]

24.  Secondary:

Change From Baseline to Week 3 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16)   [ Time Frame: Baseline and 3 weeks following the start of study drug administration ]

25.  Secondary:

Change From Baseline to Week 4 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16)   [ Time Frame: Baseline and 4 weeks following the start of study drug administration ]

26.  Secondary:

Change From Baseline to Week 6 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16)   [ Time Frame: Baseline and 6 weeks following the start of study drug administration ]

27.  Secondary:

Change From Baseline to Week 8 in the Quick Inventory of Depressive Symptomatology - 16 Items (QIDS-SR16)   [ Time Frame: Baseline and 8 weeks following the start of study drug administration ]

28.  Secondary:

Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (Q-LES-Q-SF)   [ Time Frame: Baseline and 8 weeks (or last observation after baseline) ]

29.  Secondary:

Change From Baseline to Week 4 in the Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (Q-LES-Q-SF)   [ Time Frame: Baseline and 4 weeks following the start of study drug administration ]

30.  Secondary:

Change From Baseline to Week 8 in the Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (Q-LES-Q-SF)   [ Time Frame: Baseline and 8 weeks following the start of study drug administration ]

31.  Secondary:

Change From Baseline to Endpoint (8 Weeks or Last Observation After Baseline) in Hamilton Anxiety Scale (HAM-A) Total Score   [ Time Frame: baseline and 8 weeks (or last observation after baseline) ]

32.  Secondary:

Change From Baseline to 4 Weeks in the Hamilton Anxiety Scale (HAM A) Total Score   [ Time Frame: Baseline and 4 weeks following the start of study drug administration ]

33.  Secondary:

Change From Baseline to 8 Weeks in the Hamilton Anxiety Scale (HAM A) Total Score   [ Time Frame: Baseline and 8 weeks following the start of study drug administration ]

34.  Secondary:

The Number of Responders According to the Clinical Global Impression of Change – Bipolar Version (CGI BP) Measure of Depression at Endpoint (Week 8 or Last Observation After Baseline)   [ Time Frame: Baseline and 8 weeks (or last observation after baseline) ]

35.  Secondary:

The Number of Responders According to the Clinical Global Impression of Change – Bipolar Version (CGI BP) Measure of Depression at Week 1   [ Time Frame: Baseline and 1 week following the start of study drug administration ]

36.  Secondary:

The Number of Responders According to the Clinical Global Impression of Change – Bipolar Version (CGI BP) Measure of Depression at Week 2   [ Time Frame: Baseline and 2 weeks following the start of study drug administration ]

37.  Secondary:

The Number of Responders According to the Clinical Global Impression of Change – Bipolar Version (CGI BP) Measure of Depression at Week 3   [ Time Frame: Baseline and 3 weeks following the start of study drug administration ]

38.  Secondary:

The Number of Responders According to the Clinical Global Impression of Change – Bipolar Version (CGI BP) Measure of Depression at Week 4   [ Time Frame: Baseline and 4 weeks following the start of study drug administration ]

39.  Secondary:

The Number of Responders According to the Clinical Global Impression of Change – Bipolar Version (CGI BP) Measure of Depression at Week 6   [ Time Frame: Baseline and 6 weeks following the start of study drug administration ]

40.  Secondary:

The Number of Responders According to the Clinical Global Impression of Change – Bipolar Version (CGI BP) Measure of Depression at Week 8   [ Time Frame: Baseline and 8 weeks following the start of study drug administration ]