Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150 mg/Day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

• Sponsor: Cephalon (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01305408
• Collaborator: (none)
• Enrollment: 399
• Locations: 130
• Arms: 2
• Duration (Months): 28
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of the study is to determine whether armodafinil treatment, at a dosage of 150 mg/day, is more effective than placebo treatment as adjunctive therapy to mood stabilizers for treatment of adults with major depression associated with bipolar I disorder.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Armodafinil; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 399 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dosage Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150 mg/Day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	Drug: Placebo; Matching placebo tablets, taken orally, once daily in the morning
Experimental: Armodafinil 150 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. Treatment was administered for a total of 8 weeks.	Drug: Armodafinil; Armodafinil tablets, taken orally, once daily in the morning; Other Names: Nuvigil CEP-10953

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) [Day 0 (baseline), Week 8]

   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.

Secondary Outcome Measures

1. Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score [Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

   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.

2. Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

   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.

3. Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) [Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

   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.

4. Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) [Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

   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.

5. Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression [Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

   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.

6. Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale [Day 0 (baseline), Weeks 4, 8, and last postbaseline observation (up to 8 weeks)]

   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.

7. Participants With Treatment-Emergent Adverse Events (TEAE) [Day 1 to Week 9]

   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.

8. Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score [Day 0 (baseline), last postbaseline observation (up to 8 weeks)]

   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.

9. Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score [Day 0 (baseline), last postbaseline observation (up to 8 weeks)]

   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.

10. Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score [Day 0 (baseline), last postbaseline observation (up to 8 weeks)]

    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.

11. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Actual Attempt Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Actual Attempt question records whether the participant committed a potentially self-injurious act with at least some wish to die since the last visit.

12. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Non-Suicidal Self-Injurious Behavior Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Non-Suicidal Self-Injurious Behavior question records whether the participant committed a potentially self-injurious act that was not associated with a wish to die since the last visit.

13. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Interrupted Attempt Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Interrupted Attempt question records whether the participant was interrupted by an outside circumstance from starting the potentially self-injurious act with at least some wish to die since the last visit.

14. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Aborted Attempt Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Aborted Attempt question records whether the participant began to take steps toward making a suicide attempt but stops themselves before starting the potentially self-injurious act since the last visit.

15. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Suicidal Behavior Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Suicidal Behavior question records whether in the clinician's opinion, the participant exhibited suicidal behavior since the last visit.

16. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Preparatory Acts or Behavior Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Preparatory Acts or Behavior question records whether the participant exhibited acts or preparations towards imminently making a suicide attempt since the last visit.

17. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Completed Suicide Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Completed Suicide question records whether the participant intentionally causing his/her's own death since the last visit.

18. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Wish to Be Dead Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Wish to Be Dead question records whether the participant endorses thoughts about a wish to dead or not alive anymore, or a wish to fall asleep and not wake up since the last visit.

19. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Non-Specific Active Suicidal Thoughts Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Non-Specific Active Suicidal Thoughts question records whether the participant shares general non-specific thoughts of wanting to end one's life/commit suicide since the last visit.

20. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Any Methods (Not Plan) Without Intent to Act Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Any Methods (Not Plan) Without Intent to Act question records whether the participant endorses thoughts of suicide and has thought of at least one method but has no specific plan of action since the last visit.

21. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Some Intent to Act Without a Specific Plan Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Some Intent to Act Without a Specific Plan question records whether the participant has active suicidal thoughts of killing oneself and reports having some intent to act on such thoughts since the last visit.

22. Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Specific Plan and Intent Question [Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)]

    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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Specific Plan and Intent question records whether the participant has active suicidal thoughts of killing oneself with details of plan fully or partially worked out and the participant has some intent to carry out the plan since the last visit.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• The patient has a diagnosis of bipolar I disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision) (DSM-IV-TR) criteria and is currently experiencing a major depressive episode.

• Documentation that the patient has had at least 1 previous manic or mixed episode.

• The patient has had no more than 6 mood episodes in the last year.

• The patient's current major depressive episode must have started no less than 2 weeks and no more than 12 months prior to the screening visit. The current depressive episode must have begun after the patient's current mood stabilizer regime began.

• The patient must have been taking 1 (or 2) of the following protocol-allowed mood stabilizers: lithium, valproic acid, lamotrigine, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone (only if taken in combination with lithium, valproic acid, or lamotrigine). The following criteria must also be met:

1. The mood stabilizer(s) must have been taken a minimum 4 weeks before the onset of the major depressive episode and still be taken at the time of the screening visit at dose or blood level considered appropriate for maintenance therapy by the patient's physician.

2. The patient must continue to take the same mood stabilizer(s) during the screening period; no mood stabilizer may be added during the screening period.

3. The mood stabilizer(s) must be taken for a minimum of at least 8 weeks prior to the baseline visit.

4. The dosage of the mood stabilizer(s) must be stable for a minimum of 4 weeks prior to the baseline visit.

5. The mood stabilizer(s) must be taken in an oral formulation, with the exception of risperidone, which can be either in an oral or long-acting injection formulation.

6. The patient may be taking 2 protocol-allowed mood stabilizers only if 1 of the drugs is lithium, valproic acid, or lamotrigine.

Exclusion Criteria:

• The patient has any Axis I disorder apart from bipolar I disorder that was the primary focus of treatment within 6 months of the screening visit or during the screening period.

• The patient has psychotic symptoms or has had psychosis within 4 weeks of the screening visit or during the screening period.

• The patient has current active suicidal ideation, is at imminent risk of self-harm, or has a history of significant suicidal ideation or suicide attempt at any time in the past that causes concern at present.

• The patient has a history of an eating disorder or obsessive compulsive disorder (OCD) within 6 months of the screening visit or during the screening period.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 225	Birmingham	Alabama	United States
2	Teva Investigational Site 295	Sherman Oaks	California	United States
3	Teva Investigational Site 122	Temecula	California	United States
4	Teva Investigational Site 606	Jacksonville Beach	Florida	United States
5	Teva Investigational Site 127	Lauderhill	Florida	United States
6	Teva Investigational Site 608	Tampa	Florida	United States
7	Teva Investigational Site 116	Atlanta	Georgia	United States
8	Teva Investigational Site 205	Atlanta	Georgia	United States
9	Teva Investigational Site 195	Park Ridge	Illinois	United States
10	Teva Investigational Site 611	Indianapolis	Indiana	United States
11	Teva Investigational Site 600	Lafayette	Indiana	United States
12	Teva Investigational Site 603	Watertown	Massachusetts	United States
13	Teva Investigational Site 207	Brooklyn	New York	United States
14	Teva Investigational Site 202	New York	New York	United States
15	Teva Investigational Site 110	Staten Island	New York	United States
16	Teva Investigational Site 411	Staten Island	New York	United States
17	Teva Investigational Site 614	Wilmington	North Carolina	United States
18	Teva Investigational Site 610	Cincinnati	Ohio	United States
19	Teva Investigational Site 615	Toledo	Ohio	United States
20	Teva Investigational Site 401	Oklahoma City	Oklahoma	United States
21	Teva Investigational Site 609	Oklahoma City	Oklahoma	United States
22	Teva Investigational Site 616	Oklahoma City	Oklahoma	United States
23	Teva Investigational Site 406	Allentown	Pennsylvania	United States
24	Teva Investigational Site 403	Desoto	Texas	United States
25	Teva Investigational Site 612	Friendswood	Texas	United States
26	Teva Investigational Site 408	Salt Lake City	Utah	United States
27	Teva Investigational Site 613	Kirkland	Washington	United States
28	Teva Investigational Site 605	Spokane	Washington	United States
29	Teva Investigational Site 134	Buenos Aires		Argentina
30	Teva Investigational Site 136	Buenos Aires		Argentina
31	Teva Investigational Site 881	Buenos Aires		Argentina
32	Teva Investigational Site 884	Buenos Aires		Argentina
33	Teva Investigational Site 888	Buenos Aires		Argentina
34	Teva Investigational Site 135	Córdoba Capital		Argentina
35	Teva Investigational Site 236	Córdoba		Argentina
36	Teva Investigational Site 138	La Plata, Buenos Aires		Argentina
37	Teva Investigational Site 371	La Plata		Argentina
38	Teva Investigational Site 886	La Plata		Argentina
39	Teva Investigational Site 882	Mendoza		Argentina
40	Teva Investigational Site 883	Mendoza		Argentina
41	Teva Investigational Site 885	Mendoza		Argentina
42	Teva Investigational Site 887	Mendoza		Argentina
43	Teva Investigational Site 238	Rosario		Argentina
44	Teva Investigational Site 623	Belo Horizonte		Brazil
45	Teva Investigational Site 626	Curitiba-Parana		Brazil
46	Teva Investigational Site 621	Distrito de Rubiao Junior		Brazil
47	Teva Investigational Site 627	Itapira -Sao Paulo		Brazil
48	Teva Investigational Site 624	Rio de Janeiro		Brazil
49	Teva Investigational Site 622	Salvador		Brazil
50	Teva Investigational Site 628	Sao Paolo		Brazil
51	Teva Investigational Site 248	Bourgas		Bulgaria
52	Teva Investigational Site 146	Kardzhali		Bulgaria
53	Teva Investigational Site 148	Kazanlak		Bulgaria
54	Teva Investigational Site 853	Pazardjik		Bulgaria
55	Teva Investigational Site 852	Pleven		Bulgaria
56	Teva Investigational Site 145	Plovdiv		Bulgaria
57	Teva Investigational Site 370	Ruse		Bulgaria
58	Teva Investigational Site 147	Sofia		Bulgaria
59	Teva Investigational Site 149	Sofia		Bulgaria
60	Teva Investigational Site 244	Sofia		Bulgaria
61	Teva Investigational Site 247	Sofia		Bulgaria
62	Teva Investigational Site 854	Sofia		Bulgaria
63	Teva Investigational Site 855	Sofia		Bulgaria
64	Teva Investigational Site 245	Varna		Bulgaria
65	Teva Investigational Site 851	Varna		Bulgaria
66	Teva Investigational Site 856	Varna		Bulgaria
67	Teva Investigational Site 635	Rijeka		Croatia
68	Teva Investigational Site 631	Split		Croatia
69	Teva Investigational Site 632	Zagreb		Croatia
70	Teva Investigational Site 633	Zagreb		Croatia
71	Teva Investigational Site 634	Zagreb		Croatia
72	Teva Investigational Site 716	Helsinki		Finland
73	Teva Investigational Site 717	Helsinki		Finland
74	Teva Investigational Site 719	Kangasala		Finland
75	Teva Investigational Site 718	Turku		Finland
76	Teva Investigational Site 655	Achim		Germany
77	Teva Investigational Site 656	Berlin		Germany
78	Teva Investigational Site 653	Cologne		Germany
79	Teva Investigational Site 651	Dresden		Germany
80	Teva Investigational Site 654	Freiburg		Germany
81	Teva Investigational Site 652	Mittweida		Germany
82	Teva Investigational Site 661	Budapest		Hungary
83	Teva Investigational Site 662	Budapest		Hungary
84	Teva Investigational Site 664	Budapest		Hungary
85	Teva Investigational Site 665	Gyor		Hungary
86	Teva Investigational Site 666	Nagykallo		Hungary
87	Teva Investigational Site 688	Catania		Italy
88	Teva Investigational Site 689	Firenze		Italy
89	Teva Investigational Site 686	Genova		Italy
90	Teva Investigational Site 691	Lido di Camaiore(LU)		Italy
91	Teva Investigational Site 690	Naples		Italy
92	Teva Investigational Site 687	Pisa		Italy
93	Teva Investigational Site 693	Pisa		Italy
94	Teva Investigational Site 692	Roma		Italy
95	Teva Investigational Site 259	Bialystok		Poland
96	Teva Investigational Site 257	Gdansk		Poland
97	Teva Investigational Site 258	Gdynia		Poland
98	Teva Investigational Site 155	Krakow		Poland
99	Teva Investigational Site 255	Skorzewo		Poland
100	Teva Investigational Site 861	Szczecin		Poland
101	Teva Investigational Site 157	Tuszyn		Poland
102	Teva Investigational Site 177	Belgrade		Serbia
103	Teva Investigational Site 831	Belgrade		Serbia
104	Teva Investigational Site 832	Belgrade		Serbia
105	Teva Investigational Site 835	Belgrade		Serbia
106	Teva Investigational Site 176	Kragujevac		Serbia
107	Teva Investigational Site 837	Nis		Serbia
108	Teva Investigational Site 834	Novi Knezevac		Serbia
109	Teva Investigational Site 700	Bojnice		Slovakia
110	Teva Investigational Site 699	Bratislava		Slovakia
111	Teva Investigational Site 697	Rimavska Sobota		Slovakia
112	Teva Investigational Site 696	Roznava		Slovakia
113	Teva Investigational Site 698	Trencin		Slovakia
114	Teva Investigational Site 707	Cape Town		South Africa
115	Teva Investigational Site 709	Cape Town		South Africa
116	Teva Investigational Site 712	Cape Town		South Africa
117	Teva Investigational Site 708	Centurion		South Africa
118	Teva Investigational Site 710	Johannesburg		South Africa
119	Teva Investigational Site 711	Paarl		South Africa
120	Teva Investigational Site 706	Pretoria		South Africa
121	Teva Investigational Site 181	Dnipropetrovsk		Ukraine
122	Teva Investigational Site 872	Donetsk		Ukraine
123	Teva Investigational Site 282	Kharkiv		Ukraine
124	Teva Investigational Site 281	Kiev		Ukraine
125	Teva Investigational Site 180	Lugansk		Ukraine
126	Teva Investigational Site 873	Lviv		Ukraine
127	Teva Investigational Site 875	Odessa		Ukraine
128	Teva Investigational Site 183	Poltava		Ukraine
129	Teva Investigational Site 871	s. Oleksandrivka		Ukraine
130	Teva Investigational Site 182	Vinnytsya		Ukraine

Sponsors and Collaborators

• Cephalon

Investigators

• Study Director: Sponsor's Medical Expert, Cephalon

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cephalon
• ClinicalTrials.gov Identifier: NCT01305408
• Other Study ID Numbers: C10953/3073; 2010-023623-26
• First Posted: Feb 28, 2011
• Last Update Posted: May 26, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Cephalon: Bipolar I Disorder
• Additional relevant MeSH terms: Depression; Depressive Disorder; Modafinil

Study Results

Participant Flow

Recruitment Details	Region 1: USA and Canada Region 2: Eastern European countries, Kyrgyzstan, Mongolia, Uzbekistan, Cyprus, Greece, and Turkey Region 3: Central and Northern European countries, Andorra, Australia, Iceland, Monaco, San Marino, and Vatican City Region 4: Rest of World
Pre-assignment Detail	Participants were randomized (1:1) to receive150 mg/day armodafinil or matching placebo. Randomization was stratified on the basis of the mood-stabilizing medication and region of the world.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Period Title: Overall Study
STARTED	199	200
Safety Population	198	200
Full Analysis Population	196	197
COMPLETED	167	169
NOT COMPLETED	32	31

Baseline Characteristics

Arm/Group Title	Placebo	Armodafinil 150 mg/Day	Total
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.	Total of all reporting groups
Overall Participants	199	200	399
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.7 (11.62)	45.3 (11.26)	44.5 (11.45)
Sex: Female, Male (Count of Participants)
Female	121 60.8%	120 60%	241 60.4%
Male	78 39.2%	80 40%	158 39.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 7%	22 11%	36 9%
Not Hispanic or Latino	183 92%	176 88%	359 90%
Unknown or Not Reported	2 1%	2 1%	4 1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 1%	2 0.5%
Asian	1 0.5%	2 1%	3 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	16 8%	14 7%	30 7.5%
White	176 88.4%	182 91%	358 89.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 3%	0 0%	6 1.5%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	81.2 (17.46)	80.7 (17.54)	80.9 (17.48)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	168.4 (9.32)	168.9 (9.23)	168.6 (9.27)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	28.7 (5.95)	28.2 (5.52)	28.4 (5.73)
Time Since Start of Current Depressive Episode (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	12.1 (9.10)	12.3 (9.89)	12.2 (9.49)
Time Since First Diagnosis for Bipolar (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.9 (8.72)	10.7 (8.55)	10.3 (8.63)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
Description	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.
Time Frame	Day 0 (baseline), Week 8

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	196	197
Least Squares Mean (Standard Error) [units on a scale]	-19.4 (0.99)	-20.8 (0.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Armodafinil 150 mg/Day
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2717
	Comments	Statistical tests were 2-tailed at the 0.05 level of significance.
	Method	mixed-model repeated measures (MMRM)
	Comments	Treatment, visit, treatment-by-visit interaction, concurrent mood-stabilizing medication, and region of the world used as fixed factors.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -3.76 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score
Description	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.
Time Frame	Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	196	197
Week 1 (196, 195)	2 1%	3 1.5%
Week 2 (187, 189)	13 6.5%	9 4.5%
Week 4 (181, 183)	21 10.6%	27 13.5%
Week 6 (172, 172)	29 14.6%	41 20.5%
Week 7 (167, 170)	39 19.6%	51 25.5%
Week 8 (167, 169)	46 23.1%	56 28%
Endpoint (196, 197)	41 20.6%	49 24.5%

3. Secondary Outcome

Title	Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score
Description	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.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	196	197
Week 1 (196, 195)	.5 0.3%	1 0.5%
Week 2 (187, 189)	2 1%	2 1%
Week 4 (181, 183)	5 2.5%	7 3.5%
Week 6 (172, 172)	9 4.5%	12 6%
Week 7 (167, 170)	14 7%	19 9.5%
Week 8 (167, 169)	15 7.5%	26 13%
Endpoint (196, 197)	13 6.5%	22 11%

4. Secondary Outcome

Title	Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
Description	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.
Time Frame	Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	196	197
Week 1 (196, 195)	-6.0 (6.61)	-5.3 (7.12)
Week 2 (187, 189)	-10.0 (8.71)	-8.9 (8.56)
Week 4 (181, 183)	-13.4 (9.87)	-13.5 (10.54)
Week 6 (172, 172)	-15.8 (10.42)	-17.6 (11.09)
Week 7 (167, 170)	-18.0 (11.42)	-20.2 (10.88)
Week 8 (167, 169)	-19.7 (11.30)	-21.6 (11.75)
Endpoint (196, 197)	-18.3 (11.62)	-19.5 (12.66)

5. Secondary Outcome

Title	Change From Baseline to Different Treatment Weeks in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16)
Description	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.
Time Frame	Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	196	197
Week 1 (196, 195)	-2.4 (2.92)	-2.1 (3.07)
Week 2 (187, 189)	-4.2 (3.83)	-3.4 (3.63)
Week 4 (181, 183)	-5.3 (4.05)	-5.3 (4.15)
Week 6 (172, 172)	-6.3 (4.16)	-6.7 (4.38)
Week 7 (167, 170)	-7.2 (4.49)	-7.8 (4.35)
Week 8 (167, 169)	-8.0 (4.53)	-8.3 (4.62)
Endpoint (196, 197)	-7.3 (4.73)	-7.5 (4.91)

6. Secondary Outcome

Title	Change From Baseline to Different Treatment Weeks in the Clinical Global Impression of Severity (CGI-S) for Depression
Description	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.
Time Frame	Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	196	197
Week 1 (196, 195)	-0.2 (0.49)	-0.2 (0.46)
Week 2 (187, 189)	-0.5 (0.65)	-0.5 (0.77)
Week 4 (181, 183)	-0.7 (0.76)	-0.9 (0.97)
Week 6 (172, 172)	-1.0 (0.91)	-1.2 (1.03)
Week 7 (167, 170)	-1.2 (1.08)	-1.4 (1.10)
Week 8 (167, 169)	-1.3 (1.11)	-1.6 (1.19)
Endpoint (196, 197)	-1.2 (1.14)	-1.4 (1.25)

7. Secondary Outcome

Title	Change From Baseline to Weeks 4, 8 and Endpoint in the Global Assessment for Functioning (GAF) Scale
Description	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.
Time Frame	Day 0 (baseline), Weeks 4, 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	196	197
Week 4 (181, 183)	5.8 (7.39)	8.2 (10.39)
Week 8 (167, 169)	11.5 (10.42)	15.3 (11.72)
Endpoint (189, 192)	10.6 (10.42)	13.6 (12.38)

8. Secondary Outcome

Title	Participants With Treatment-Emergent Adverse Events (TEAE)
Description	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.
Time Frame	Day 1 to Week 9

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
>=1 adverse event	71 35.7%	89 44.5%
Severe adverse event	4 2%	4 2%
Treatment-related adverse event	32 16.1%	53 26.5%
Deaths	0 0%	0 0%
Other serious adverse events	6 3%	5 2.5%
Withdrawn from study due to adverse events	10 5%	7 3.5%
Protocol-defined adverse events	3 1.5%	3 1.5%

9. Secondary Outcome

Title	Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score
Description	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.
Time Frame	Day 0 (baseline), last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	196	198
Mean (Standard Deviation) [units on a scale]	-1.0 (2.45)	-0.9 (3.19)

10. Secondary Outcome

Title	Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score
Description	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.
Time Frame	Day 0 (baseline), last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	190	194
Mean (Standard Deviation) [units on a scale]	-4.2 (4.53)	-4.3 (5.37)

11. Secondary Outcome

Title	Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score
Description	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.
Time Frame	Day 0 (baseline), last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	190	192
Mean (Standard Deviation) [units on a scale]	-7.0 (6.62)	-7.1 (6.91)

12. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Actual Attempt Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Actual Attempt question records whether the participant committed a potentially self-injurious act with at least some wish to die since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	0 0%	0 0%
Week 2 (187, 189)	0 0%	0 0%
Week 4 (181, 183)	0 0%	0 0%
Week 6 (172, 172)	0 0%	0 0%
Week 7 (167, 170)	0 0%	0 0%
Week 8 (167, 169)	0 0%	0 0%
Endpoint (196, 198)	0 0%	0 0%

13. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Non-Suicidal Self-Injurious Behavior Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Non-Suicidal Self-Injurious Behavior question records whether the participant committed a potentially self-injurious act that was not associated with a wish to die since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	0 0%	0 0%
Week 2 (187, 189)	0 0%	0 0%
Week 4 (181, 183)	0 0%	0 0%
Week 6 (172, 172)	0 0%	0 0%
Week 7 (167, 170)	0 0%	0 0%
Week 8 (167, 169)	0 0%	0 0%
Endpoint (196, 198)	0 0%	0 0%

14. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Interrupted Attempt Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Interrupted Attempt question records whether the participant was interrupted by an outside circumstance from starting the potentially self-injurious act with at least some wish to die since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	0 0%	0 0%
Week 2 (187, 189)	0 0%	0 0%
Week 4 (181, 183)	0 0%	0 0%
Week 6 (172, 172)	0 0%	0 0%
Week 7 (167, 170)	0 0%	0 0%
Week 8 (167, 169)	0 0%	0 0%
Endpoint (196, 198)	0 0%	0 0%

15. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Aborted Attempt Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Aborted Attempt question records whether the participant began to take steps toward making a suicide attempt but stops themselves before starting the potentially self-injurious act since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	0 0%	0 0%
Week 2 (187, 189)	0 0%	0 0%
Week 4 (181, 183)	0 0%	0 0%
Week 6 (172, 172)	0 0%	0 0%
Week 7 (167, 170)	0 0%	0 0%
Week 8 (167, 169)	0 0%	0 0%
Endpoint (196, 198)	0 0%	0 0%

16. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Suicidal Behavior Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Suicidal Behavior question records whether in the clinician's opinion, the participant exhibited suicidal behavior since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	0 0%	0 0%
Week 2 (187, 189)	0 0%	0 0%
Week 4 (181, 183)	0 0%	0 0%
Week 6 (172, 172)	0 0%	0 0%
Week 7 (167, 170)	0 0%	0 0%
Week 8 (167, 169)	0 0%	0 0%
Endpoint (196, 198)	0 0%	0 0%

17. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Preparatory Acts or Behavior Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Preparatory Acts or Behavior question records whether the participant exhibited acts or preparations towards imminently making a suicide attempt since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	0 0%	0 0%
Week 2 (187, 189)	0 0%	0 0%
Week 4 (181, 183)	0 0%	0 0%
Week 6 (172, 172)	0 0%	0 0%
Week 7 (167, 170)	0 0%	0 0%
Week 8 (167, 169)	0 0%	0 0%
Endpoint (196, 198)	0 0%	0 0%

18. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Behavior - Completed Suicide Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Behavior - Completed Suicide question records whether the participant intentionally causing his/her's own death since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	0 0%	0 0%
Week 2 (187, 189)	0 0%	0 0%
Week 4 (181, 183)	0 0%	0 0%
Week 6 (172, 172)	0 0%	0 0%
Week 7 (167, 170)	0 0%	0 0%
Week 8 (167, 169)	0 0%	0 0%
Endpoint (196, 198)	0 0%	0 0%

19. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Wish to Be Dead Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Wish to Be Dead question records whether the participant endorses thoughts about a wish to dead or not alive anymore, or a wish to fall asleep and not wake up since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	6 3%	5 2.5%
Week 2 (187, 189)	2 1%	6 3%
Week 4 (181, 183)	1 0.5%	7 3.5%
Week 6 (172, 172)	2 1%	3 1.5%
Week 7 (167, 170)	2 1%	2 1%
Week 8 (167, 169)	1 0.5%	3 1.5%
Endpoint (196, 198)	2 1%	4 2%

20. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Non-Specific Active Suicidal Thoughts Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Non-Specific Active Suicidal Thoughts question records whether the participant shares general non-specific thoughts of wanting to end one's life/commit suicide since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (196, 195)	2 1%	0 0%
Week 2 (187, 189)	0 0%	0 0%
Week 4 (181, 183)	0 0%	1 0.5%
Week 6 (172, 172)	0 0%	1 0.5%
Week 7 (167, 170)	0 0%	1 0.5%
Week 8 (167, 169)	0 0%	1 0.5%
Endpoint (196, 198)	0 0%	1 0.5%

21. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Any Methods (Not Plan) Without Intent to Act Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Any Methods (Not Plan) Without Intent to Act question records whether the participant endorses thoughts of suicide and has thought of at least one method but has no specific plan of action since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES, or based on the judgment of the assessor. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (6, 5)	1 0.5%	1 0.5%
Week 2 (2, 6)	0 0%	0 0%
Week 4 (1, 7)	0 0%	0 0%
Week 6 (1, 3)	0 0%	0 0%
Week 7 (2, 2)	0 0%	0 0%
Week 8 (1, 3)	0 0%	0 0%
Endpoint (8, 12)	1 0.5%	0 0%

22. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Some Intent to Act Without a Specific Plan Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Some Intent to Act Without a Specific Plan question records whether the participant has active suicidal thoughts of killing oneself and reports having some intent to act on such thoughts since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES, or based on the judgment of the assessor. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (6, 5)	0 0%	0 0%
Week 2 (2, 6)	0 0%	0 0%
Week 4 (1, 7)	0 0%	0 0%
Week 6 (1, 3)	0 0%	0 0%
Week 7 (2, 2)	0 0%	0 0%
Week 8 (1, 3)	0 0%	0 0%
Endpoint (8, 12)	0 0%	0 0%

23. Secondary Outcome

Title	Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) For Weeks 1, 2, 4, 6, 7, 8, and Endpoint For the Suicidal Ideation - Specific Plan and Intent Question
Description	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 C-SSRS-B (baseline) was performed at screening and the C-SSRS-SLV ('Since Last Visit') was performed at baseline and weeks 1, 2, 4, 6, 7, and 8 or last postbaseline observation. The Suicidal Ideation - Specific Plan and Intent question records whether the participant has active suicidal thoughts of killing oneself with details of plan fully or partially worked out and the participant has some intent to carry out the plan since the last visit.
Time Frame	Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set includes randomized participants who took 1 or more doses of study drug. This question is asked if the answer to the 'Non-Specific Active Suicidal Thoughts' question was YES, or based on the judgment of the assessor. The number analyzed includes participants with treatment assessments at the indicated time period.

Arm/Group Title	Placebo	Armodafinil 150 mg/Day
Arm/Group Description	Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.	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. Treatment was administered for a total of 8 weeks.
Measure Participants	198	200
Week 1 (6, 5)	1 0.5%	0 0%
Week 2 (2, 6)	0 0%	0 0%
Week 4 (1, 7)	0 0%	0 0%
Week 6 (1, 3)	0 0%	0 0%
Week 7 (2, 2)	0 0%	0 0%
Week 8 (1, 3)	0 0%	0 0%
Endpoint (8, 12)	1 0.5%	0 0%

Adverse Events

Time Frame	Day 1 to Week 9
Arm/Group Title	Armodafinil 150 mg/Day		Placebo
Arm/Group Description	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. Treatment was administered for a total of 8 weeks.		Participants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.
All Cause Mortality
	Armodafinil 150 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Armodafinil 150 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/200 (2.5%)		6/198 (3%)
Hepatobiliary disorders
Cholecystitis chronic	1/200 (0.5%)	1	0/198 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/200 (0%)	0	1/198 (0.5%)	1
Pregnancy, puerperium and perinatal conditions
Unintended pregnancy	0/200 (0%)	0	1/198 (0.5%)	1
Psychiatric disorders
Anxiety	1/200 (0.5%)	1	0/198 (0%)	0
Bipolar I disorder	1/200 (0.5%)	1	0/198 (0%)	0
Depression	1/200 (0.5%)	1	0/198 (0%)	0
Hypomania	0/200 (0%)	0	1/198 (0.5%)	1
Insomnia	1/200 (0.5%)	1	0/198 (0%)	0
Suicidal ideation	0/200 (0%)	0	1/198 (0.5%)	1
Suicide attempt	1/200 (0.5%)	1	0/198 (0%)	0
Reproductive system and breast disorders
Cervical dysplasia	0/200 (0%)	0	1/198 (0.5%)	1
Skin and subcutaneous tissue disorders
Toxic skin eruption	0/200 (0%)	0	1/198 (0.5%)	1
Social circumstances
Social stay hospitalisation	1/200 (0.5%)	1	0/198 (0%)	0
Other (Not Including Serious) Adverse Events
	Armodafinil 150 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/200 (18.5%)		21/198 (10.6%)
Gastrointestinal disorders
Nausea	12/200 (6%)	13	7/198 (3.5%)	7
Nervous system disorders
Headache	29/200 (14.5%)	35	15/198 (7.6%)	17

Limitations/Caveats

[Not Specified]

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.