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

• Sponsor: Cephalon (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01121536
• Collaborator: (none)
• Enrollment: 867
• Locations: 158
• Arm: 1
• Actual Duration (Months): 42.1
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of long term (6 months) armodafinil treatment as adjunctive therapy to mood-stabilizing medications in adults with bipolar I disorder.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 867 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 6-Month, Open-Label, Flexible-Dosage (150 to 200 mg/Day) Extension Study of the Safety and Efficacy of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder
• Actual Study Start Date: Apr 30, 2010
• Actual Primary Completion Date: Oct 31, 2013
• Actual Study Completion Date: Oct 31, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Armodafinil 150-200 mg/day Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.

Drug: Armodafinil; Armodafinil tablets, taken orally, once daily in the morning; Other Names: CEP-10953 Nuvigil

Outcome Measures

Primary Outcome Measures

1. Participants With Treatment-Emergent Adverse Events (TEAE) [Day 1 up to Month 6]

   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.

2. Participants With Clinically Significant Abnormal Serum Chemistry Values [Day 1 to Month 6]

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

3. Participants With Clinically Significant Abnormal Hematology Values [Day 1 to Month 6]

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

4. Participants With Clinically Significant Abnormal Urinalysis Values [Day 1 to Month 6]

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

5. Participants With Clinically Significant Abnormal Vital Signs Values [Day 1 to Month 6]

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

6. Change From Baseline to Endpoint in Electrocardiogram (ECG) Values [Day 0 (baseline), Month 6 or last post-baseline observation]

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

7. Physical Examination Shifts From Baseline to Endpoint [Day 0 (baseline), Month 6 (or last post-baseline observation)]

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

8. Change From Baseline to Endpoint in Body Weight [Day 0 (baseline), Month 6 (or last post-baseline observation)]

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

9. Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score [Day 0 (baseline), Month 6 or last post-baseline observation]

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

10. Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV) [Day 1, Week 1, Months 1, 2, 4 and 6 or last post-baseline visit]

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

11. Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score [Day 0 (baseline), Month 6 (or last post-baseline observation)]

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

12. Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score [Day 0 (baseline), Month 6 or last post-baseline observation]

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

Secondary Outcome Measures

1. Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) [Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline 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. Baseline was the score before the first dose of study drug in the double-blind study.

2. Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16) [Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)]

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

3. Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression [Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)]

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

4. Change From Baseline to Endpoint in the Global Assessment for Functioning (GAF) Scale [Day 0 (baseline), Month 6 or the last post-baseline assessment)]

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

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• The patient has completed 8 weeks of treatment in a Cephalon-sponsored Phase 3, double-blind study of armodafinil treatment in patients with major depression associated with bipolar I disorder.

• The patient met criteria for enrollment in the previous double-blind study and, in the opinion of the investigator, is in need of continued treatment for depression.

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

1. The mood stabilizers must be taken in an oral formulation, with the exception of risperidone, which can be either in an oral or long-acting injection formulation.

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

3. The patient must be judged by the investigator to be compliant with treatment with the mood stabilizer(s).

4. The patient must be willing to continue treatment with the same protocol-allowed mood stabilizer(s) at dosages considered appropriate by the investigator.

• The patient has a Young Mania Rating Scale (YMRS) total score of 14 or less at the enrollment visit. Patients who have a YMRS score of 12 through 14 must be discussed with the medical monitor to determine their suitability for enrollment.

Key Exclusion Criteria:

• The patient has any Axis I or Axis II disorder apart from bipolar I disorder that became the primary focus of treatment during the double-blind study.

• The patient has psychotic symptoms or had psychosis during the double-blind study.

• 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 met criteria for alcohol or substance abuse or dependence (with the exception of nicotine dependence) during the double-blind study.

• The patient has any history of homicidal ideation or significant aggression or currently has homicidal or significant aggressive ideation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 113	Birmingham	Alabama	United States	35216
2	Teva Investigational Site 225	Birmingham	Alabama	United States	35226
3	Teva Investigational Site 229	Anaheim	California	United States	92804
4	Teva Investigational Site 217	Cerritos	California	United States	90703
5	Teva Investigational Site 223	Cerritos	California	United States	90703
6	Teva Investigational Site 115	Garden Grove	California	United States	92845
7	Teva Investigational Site 121	Imperial	California	United States	92251
8	Teva Investigational Site 303	Oceanside	California	United States	92056
9	Teva Investigational Site 400	Oceanside	California	United States	92056
10	Teva Investigational Site 200	Pico Rivera	California	United States	90660
11	Teva Investigational Site 128	San Diego	California	United States	92123
12	Teva Investigational Site 201	San Diego	California	United States	92126
13	Teva Investigational Site 192	Santa Ana	California	United States	92705
14	Teva Investigational Site 292	Santa Ana	California	United States	92705
15	Teva Investigational Site 295	Sherman Oaks	California	United States	91403
16	Teva Investigational Site 122	Temecula	California	United States	92591
17	Teva Investigational Site 131	Gainesville	Florida	United States	32607
18	Teva Investigational Site 606	Jacksonville Beach	Florida	United States	32250
19	Teva Investigational Site 132	Jacksonville	Florida	United States	32256
20	Teva Investigational Site 127	Lauderhill	Florida	United States	33319
21	Teva Investigational Site 119	North Miami	Florida	United States	33161
22	Teva Investigational Site 118	Tampa	Florida	United States	33613
23	Teva Investigational Site 608	Tampa	Florida	United States	33613
24	Teva Investigational Site 205	Atlanta	Georgia	United States	30308
25	Teva Investigational Site 116	Atlanta	Georgia	United States	30328
26	Teva Investigational Site 204	Smyrna	Georgia	United States	30080
27	Teva Investigational Site 107	Naperville	Illinois	United States	60563
28	Teva Investigational Site 301	Naperville	Illinois	United States	60563
29	Teva Investigational Site 219	Oakbrook Terrace	Illinois	United States	60181
30	Teva Investigational Site 195	Park Ridge	Illinois	United States	60068
31	Teva Investigational Site 600	Lafayette	Indiana	United States	47905
32	Teva Investigational Site 300	Pikesville	Maryland	United States	21208
33	Teva Investigational Site 603	Watertown	Massachusetts	United States	02472
34	Teva Investigational Site 290	Flowood	Mississippi	United States	39232
35	Teva Investigational Site 133	Saint Louis	Missouri	United States	63139
36	Teva Investigational Site 103	Mount Laurel	New Jersey	United States	08054
37	Teva Investigational Site 212	Mount Laurel	New Jersey	United States	08054
38	Teva Investigational Site 193	Albuquerque	New Mexico	United States	87109
39	Teva Investigational Site 207	Brooklyn	New York	United States	11201
40	Teva Investigational Site 104	Brooklyn	New York	United States	11235
41	Teva Investigational Site 202	New York	New York	United States	10023
42	Teva Investigational Site 129	Rochester	New York	United States	14618
43	Teva Investigational Site 411	Staten Island	New York	United States	10305
44	Teva Investigational Site 110	Staten Island	New York	United States	10312
45	Teva Investigational Site 105	Raleigh	North Carolina	United States	27609
46	Teva Investigational Site 190	Beachwood	Ohio	United States	44125
47	Teva Investigational Site 213	Canton	Ohio	United States	44718
48	Teva Investigational Site 610	Cincinnati	Ohio	United States	45267
49	Teva Investigational Site 102	Dayton	Ohio	United States	45408
50	Teva Investigational Site 401	Oklahoma City	Oklahoma	United States	73103
51	Teva Investigational Site 609	Oklahoma City	Oklahoma	United States	73112
52	Teva Investigational Site 616	Oklahoma City	Oklahoma	United States	73112
53	Teva Investigational Site 406	Allentown	Pennsylvania	United States	18104
54	Teva Investigational Site 117	Media	Pennsylvania	United States	19063
55	Teva Investigational Site 106	Memphis	Tennessee	United States	38119
56	Teva Investigational Site 111	Austin	Texas	United States	78756
57	Teva Investigational Site 403	DeSoto	Texas	United States	75115
58	Teva Investigational Site 612	Friendswood	Texas	United States	77546
59	Teva Investigational Site 228	Houston	Texas	United States	77090
60	Teva Investigational Site 224	Irving	Texas	United States	75062
61	Teva Investigational Site 409	Orem	Utah	United States	84058
62	Teva Investigational Site 408	Salt Lake City	Utah	United States	84107
63	Teva Investigational Site 404	Richmond	Virginia	United States	23230
64	Teva Investigational Site 100	Bellevue	Washington	United States	98007
65	Teva Investigational Site 613	Kirkland	Washington	United States	98033
66	Teva Investigational Site 605	Spokane	Washington	United States	99204
67	Teva Investigational Site 237	Buenos Aires		Argentina	1428
68	Teva Investigational Site 450	Buenos Aires		Argentina	C1012AAU
69	Teva Investigational Site 881	Buenos Aires		Argentina	C1058AAJ
70	Teva Investigational Site 884	Buenos Aires		Argentina	C1117ABH
71	Teva Investigational Site 136	Buenos Aires		Argentina	C1405BOA
72	Teva Investigational Site 134	Buenos Aires		Argentina	C1425AHQ
73	Teva Investigational Site 235	Buenos Aires		Argentina	C1425CDC
74	Teva Investigational Site 462	Buenos Aires		Argentina
75	Teva Investigational Site 135	Cordoba		Argentina	5004ALB
76	Teva Investigational Site 236	Cordoba		Argentina	X5009BIN
77	Teva Investigational Site 138	La Plata, Buenos Aires		Argentina	01900
78	Teva Investigational Site 371	La Plata		Argentina	41515
79	Teva Investigational Site 238	Rosario		Argentina	2000
80	Teva Investigational Site 141	Brisbane		Australia	4053
81	Teva Investigational Site 240	Malvern		Australia	3144
82	Teva Investigational Site 624	Rio de Janeiro		Brazil	22270-060
83	Teva Investigational Site 248	Bourgas		Bulgaria	8000
84	Teva Investigational Site 146	Kardzhali		Bulgaria	06600
85	Teva Investigational Site 148	Kazanlak		Bulgaria	6100
86	Teva Investigational Site 853	Pazardjik		Bulgaria	4400
87	Teva Investigational Site 852	Pleven		Bulgaria	5800
88	Teva Investigational Site 249	Plovdiv		Bulgaria	4000
89	Teva Investigational Site 145	Plovdiv		Bulgaria	4002
90	Teva Investigational Site 370	Ruse		Bulgaria	7003
91	Teva Investigational Site 147	Sofia		Bulgaria	1377
92	Teva Investigational Site 854	Sofia		Bulgaria	1431
93	Teva Investigational Site 855	Sofia		Bulgaria	1431
94	Teva Investigational Site 247	Sofia		Bulgaria	1632
95	Teva Investigational Site 851	Varna		Bulgaria	9002
96	Teva Investigational Site 245	Varna		Bulgaria	9010
97	Teva Investigational Site 198	Kelowna		Canada	V1Y 1Z9
98	Teva Investigational Site 296	Mississauga		Canada	L5M 4N4
99	Teva Investigational Site 196	Mississauga		Canada	L5M4N4
100	Teva Investigational Site 299	Penticton		Canada	V2A 4M4
101	Teva Investigational Site 635	Rijeka		Croatia	51000
102	Teva Investigational Site 633	Zagreb		Croatia	10090
103	Teva Investigational Site 634	Zagreb		Croatia	10090
104	Teva Investigational Site 286	Dole		France	39100
105	Teva Investigational Site 153	Nimes		France	30029
106	Teva Investigational Site 655	Achim		Germany	28832
107	Teva Investigational Site 651	Dresden		Germany	01307
108	Teva Investigational Site 661	Budapest		Hungary	1032
109	Teva Investigational Site 664	Budapest		Hungary	1036
110	Teva Investigational Site 662	Budapest		Hungary	1083
111	Teva Investigational Site 666	Nagykallo		Hungary	4321
112	Teva Investigational Site 688	Catania		Italy	95124
113	Teva Investigational Site 689	Firenze		Italy	50134
114	Teva Investigational Site 687	Pisa		Italy	56126
115	Teva Investigational Site 692	Rome		Italy	00193
116	Teva Investigational Site 259	Bialystok		Poland	15-879
117	Teva Investigational Site 258	Gdansk		Poland	80-282
118	Teva Investigational Site 257	Gdansk		Poland	80952
119	Teva Investigational Site 156	Kielce		Poland	25-317
120	Teva Investigational Site 155	Krakow		Poland	31-526
121	Teva Investigational Site 256	Leszno		Poland	64-100
122	Teva Investigational Site 255	Skorzewo		Poland	60-185
123	Teva Investigational Site 861	Szczecin		Poland	71-460
124	Teva Investigational Site 157	Tuszyn		Poland	95-080
125	Teva Investigational Site 832	Belgrade		Serbia	11 000
126	Teva Investigational Site 175	Belgrade		Serbia	11000
127	Teva Investigational Site 177	Belgrade		Serbia	11000
128	Teva Investigational Site 831	Belgrade		Serbia	11000
129	Teva Investigational Site 833	Belgrade		Serbia	11000
130	Teva Investigational Site 176	Kragujevac		Serbia	34000
131	Teva Investigational Site 837	Nis		Serbia	18000
132	Teva Investigational Site 834	Novi Knezevac		Serbia	23330
133	Teva Investigational Site 699	Bratislava		Slovakia	82007
134	Teva Investigational Site 697	Rimavska Sobota		Slovakia	97901
135	Teva Investigational Site 696	Roznava		Slovakia	04801
136	Teva Investigational Site 698	Trencin		Slovakia	91101
137	Teva Investigational Site 712	Cape Town		South Africa	7530
138	Teva Investigational Site 709	Cape Town		South Africa	7708
139	Teva Investigational Site 708	Centurion		South Africa	0046
140	Teva Investigational Site 710	Johannesburg		South Africa	2195
141	Teva Investigational Site 711	Paarl		South Africa	7646
142	Teva Investigational Site 706	Pretoria		South Africa	0181
143	Teva Investigational Site 336	Alcoy		Spain	03804
144	Teva Investigational Site 434	Coslada (Madrid)		Spain	28822
145	Teva Investigational Site 430	Vitoria-Gasteiz		Spain	01006
146	Teva Investigational Site 433	Vitoria		Spain	01004
147	Teva Investigational Site 181	Dnipropetrovsk		Ukraine	49027
148	Teva Investigational Site 872	Donetsk		Ukraine	83099
149	Teva Investigational Site 282	Kharkiv		Ukraine	61068
150	Teva Investigational Site 281	Kiev		Ukraine	4080
151	Teva Investigational Site 180	Lugansk		Ukraine	91045
152	Teva Investigational Site 873	Lviv		Ukraine	79012
153	Teva Investigational Site 280	Odessa		Ukraine	65014
154	Teva Investigational Site 875	Odessa		Ukraine	65014
155	Teva Investigational Site 183	Poltava		Ukraine	36006
156	Teva Investigational Site 871	S. Oleksandrivka		Ukraine	65128
157	Teva Investigational Site 184	Simferopol		Ukraine	95006
158	Teva Investigational Site 182	Vinnytsya		Ukraine	21018

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: NCT01121536
• Other Study ID Numbers: C10953/3074; 2009-016648-38
• First Posted: May 12, 2010
• Last Update Posted: Sep 21, 2018
• Last Verified: Aug 1, 2018

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

Study Results

Participant Flow

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

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Period Title: Overall Study
STARTED	867
Safety Population	863
Full Analysis Population	859
COMPLETED	506
NOT COMPLETED	361

Baseline Characteristics

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Overall Participants	867
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.2 (10.96)
Sex: Female, Male (Count of Participants)
Female	525 60.6%
Male	342 39.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	91 10.5%
Not Hispanic or Latino	752 86.7%
Unknown or Not Reported	24 2.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.1%
Asian	10 1.2%
Native Hawaiian or Other Pacific Islander	1 0.1%
Black or African American	118 13.6%
White	709 81.8%
More than one race	0 0%
Unknown or Not Reported	28 3.2%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	83.7 (19.75)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	168.8 (9.54)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.4 (6.43)

Outcome Measures

1. Primary 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 up to Month 6

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	863
>=1 adverse event	423 48.8%
Severe adverse event	26 3%
Treatment-related adverse event	219 25.3%
Deaths	0 0%
Other serious adverse events	27 3.1%
Withdrawn from study due to adverse events	57 6.6%
Protocol-defined adverse events	19 2.2%

2. Primary Outcome

Title	Participants With Clinically Significant Abnormal Serum Chemistry Values
Description	Summary of serum chemistry tests in which at least one participant had a during study value that was clinically significant abnormal. The test name and criterion for clinically significant abnormal appear in each row. ULN=upper limit of normal BUN=Blood Urea Nitrogen; Uric acid has a normal range of 125-494 μmol/L. Criterion for clinically significant abnormal are different for men and women. GGT = gamma-glutamyl transpeptidase with a normal range of 4-61 U/L ALT = alanine aminotransferase with a normal range of 6-43 U/L BUN = blood urea nitrogen with a normal range of 1.4-8.6 mmol/L AST = aspartate aminotransferase with a normal range of 9-36 U/L
Time Frame	Day 1 to Month 6

Outcome Measure Data

Analysis Population Description

Safety population with post-baseline serum chemistry assessments

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	763
>=1 clinical significant value	41 4.7%
Uric Acid, M>=625, F>=506 μmol/L	17 2%
GGT, >=3*ULN	16 1.8%
ALT, >=3*ULN	7 0.8%
BUN, >=10.71 mmol/L	7 0.8%
AST, >=3*ULN	3 0.3%

3. Primary Outcome

Title	Participants With Clinically Significant Abnormal Hematology Values
Description	Summary of hematology tests in which at least one participant had a during study value that was clinically significant abnormal. The test name and criterion for clinically significant abnormal appear in each row. ULN=upper limit of normal WBC - white blood cell counts with a normal range of 3.8-10.7 10^9/L. Hemoglobin with a normal range of 115-181 g/L Hematocrit with a normal range of 0.34-0.54 L/L Platelet counts with a normal range of 130-400 10^9/L ANC= absolute neutrophil counts with a normal range of 1.96-7.23 10^9/L
Time Frame	Day 1 to Month 6

Outcome Measure Data

Analysis Population Description

Safety population with post-baseline hematology assessments

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	757
>=1 clinical significant value	13 1.5%
WBC, <=3*10^9/L	5 0.6%
Hemoglobin, M<=115, F<=95 g/L	4 0.5%
Hematocrit, M<0.37, F<0.32 L/L	8 0.9%
Platelets, <=75*10^9/L	1 0.1%
ANC, <=1*10^9/L	2 0.2%

4. Primary Outcome

Title	Participants With Clinically Significant Abnormal Urinalysis Values
Description	Summary of urinalysis tests in which at least one participant had a during study value that was clinically significant abnormal. Criterion for clinically significant abnormal urinalysis tests was >=2 unit increase from baseline.
Time Frame	Day 1 to Month 6

Outcome Measure Data

Analysis Population Description

Safety population with post-baseline urinalysis assessments

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	761
>=1 clinical significant value	28 3.2%
Urine hemoglobin	22 2.5%
Urine glucose	2 0.2%
Ketones	2 0.2%
Urine total protein	2 0.2%

5. Primary Outcome

Title	Participants With Clinically Significant Abnormal Vital Signs Values
Description	Summary of vital signs tests in which at least one participant had a during study value that was clinically significant abnormal. Criterion for clinically significant abnormal vital signs are based on FDA Neuropharmacological Division criteria: Pulse high: >=120 beats per minute (bpm) and increase of >=15 bpm from baseline Pulse low: <=50 bpm and decrease of >=15 bpm from baseline Sitting systolic blood pressure high: >=180 mm Hg and increase of >=20 mm Hg from baseline Sitting systolic blood pressure low: <=90 mm Hg and decrease of >=20 mm Hg from baseline Sitting diastolic blood pressure high: >=105 mm Hg and increase of >=15 mm Hg from baseline Sitting diastolic blood pressure low: <=50 mm Hg and decrease of >=15 mm Hg from baseline
Time Frame	Day 1 to Month 6

Outcome Measure Data

Analysis Population Description

Safety population with post-baseline vital signs assessments

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	860
>=1 clinical significant value	19 2.2%
Pulse high	2 0.2%
Pulse low	2 0.2%
Sitting systolic blood pressure high	3 0.3%
Sitting systolic blood pressure low	8 0.9%
Sitting diastolic blood pressure high	5 0.6%
Sitting diastolic blood pressure low	2 0.2%

6. Primary Outcome

Title	Change From Baseline to Endpoint in Electrocardiogram (ECG) Values
Description	ECG was conducted at baseline which was before the first dose of study drug in the double-blind study, and at the month-6 visit of the open-label study (or early termination). RR= inter-beat intervals
Time Frame	Day 0 (baseline), Month 6 or last post-baseline observation

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	759
PR interval	0.2 (16.60)
QRS interval	0.0 (7.03)
QT interval	1.4 (25.66)
QTc interval Bazett	2.2 (19.50)
QTc interval Fredericia	1.9 (15.36)
RR interval	-2.2 (137.98)

7. Primary Outcome

Title	Physical Examination Shifts From Baseline to Endpoint
Description	Baseline is the day prior to double-blind treatment. Assessments are summarized as normal or abnormal. The first assessment is the baseline assessment followed by the endpoint assessment. For example 'normal/abnormal' indicates participants who were normal at baseline and abnormal at endpoint. HEENT = Head, Eye, Ear, Nose and Throat exam
Time Frame	Day 0 (baseline), Month 6 (or last post-baseline observation)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	863
General appearance; normal/normal	714 82.4%
General appearance; normal/abnormal	8 0.9%
General appearance; abnormal/normal	23 2.7%
General appearance; abnormal/abnormal	40 4.6%
HEENT: normal/normal	753 86.9%
HEENT: normal/abnormal	3 0.3%
HEENT: abnormal/normal	15 1.7%
HEENT: abnormal/abnormal	13 1.5%
Chest+lungs: normal/normal	780 90%
Chest+lungs: normal/abnormal	0 0%
Chest+lungs: abnormal/normal	5 0.6%
Chest+lungs: abnormal/abnormal	0 0%
Heart: normal/normal	781 90.1%
Heart: normal/abnormal	2 0.2%
Heart: abnormal/normal	1 0.1%
Heart: abnormal/abnormal	1 0.1%
Abdomen: normal/normal	751 86.6%
Abdomen: normal/abnormal	5 0.6%
Abdomen: abnormal/normal	16 1.8%
Abdomen: abnormal/abnormal	13 1.5%
Musculoskeletal: normal/normal	756 87.2%
Musculoskeletal: normal/abnormal	7 0.8%
Musculoskeletal: abnormal/normal	11 1.3%
Musculoskeletal: abnormal/abnormal	11 1.3%
Skin: normal/normal	707 81.5%
Skin: normal/abnormal	9 1%
Skin: abnormal/normal	41 4.7%
Skin: abnormal/abnormal	28 3.2%
Lymph nodes: normal/normal	779 89.9%
Lymph nodes: normal/abnormal	0 0%
Lymph nodes: abnormal/normal	0 0%
Lymph nodes: abnormal/abnormal	1 0.1%
Neurological: normal/normal	777 89.6%
Neurological: normal/abnormal	2 0.2%
Neurological: abnormal/normal	2 0.2%
Neurological: abnormal/abnormal	3 0.3%

8. Secondary Outcome

Title	Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
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. Baseline was the score before the first dose of study drug in the double-blind study.
Time Frame	Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	859
Week 1 (837)	-23.7 (12.10)
Month 1 (793)	-25.8 (11.61)
Month 2 (716)	-27.6 (11.38)
Month 4 (578)	-29.2 (11.68)
Month 6 (503)	-29.7 (12.06)
Endpoint (857)	-27.5 (13.08)

9. Primary Outcome

Title	Change From Baseline to Endpoint in Body Weight
Description	Baseline was the score before the first dose of study drug in the double-blind study.
Time Frame	Day 0 (baseline), Month 6 (or last post-baseline observation)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	788
Mean (Standard Deviation) [kg]	-0.8 (5.67)

10. Primary 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. Baseline was the score before the first dose of study drug in the double-blind study.
Time Frame	Day 0 (baseline), Month 6 or last post-baseline observation

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 (double-blind study) and treatment assessments during the open-label study.

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	858
Mean (Standard Deviation) [units on a scale]	-0.7 (4.28)

11. Primary Outcome

Title	Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV)
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 number of participants who had findings on any of the C-SSRS-SLV (SLV=since last visit) categories at any of the time frames are indicated. - C-SSRS=Columbia Suicide Severity Rating Scale
Time Frame	Day 1, Week 1, Months 1, 2, 4 and 6 or last post-baseline visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	863
Suicidal behavior - Actual attempt	1 0.1%
Non-suicidal self-injurious behaviour	1 0.1%
Suicidal behavior - Interrupted attempt	0 0%
Suicidal behavior - Aborted attempt	0 0%
Suicidal behavior - suicidal behavior	0 0%
Suicidal behavior - Preparatory acts/behavior	1 0.1%
Suicidal behavior - Completed suicide	0 0%
Suicidal ideation - Wish to be dead	15 1.7%
Non-specific active suicidal thoughts	4 0.5%
Any methods (not plan) w/o intent to act	2 0.2%
Some intent to act, w/o specific plan	1 0.1%
Suicidal ideation - Specific plan and intent	1 0.1%

12. Secondary Outcome

Title	Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16)
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. Baseline was the score before the first dose of study drug in the double-blind study.
Time Frame	Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	859
Week 1 (838)	-9.3 (4.68)
Month 1 (793)	-10.0 (4.47)
Month 2 (716)	-10.6 (4.52)
Month 4 (578)	-11.1 (4.70)
Month 6 (503)	-11.3 (4.69)
Endpoint (857)	-10.6 (5.07)

13. Secondary Outcome

Title	Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression
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. Baseline was the score before the first dose of study drug in the double-blind study.
Time Frame	Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	859
Week 1 (838)	-1.7 (1.17)
Month 1 (791)	-1.9 (1.17)
Month 2 (716)	-2.0 (1.18)
Month 4 (578)	-2.2 (1.16)
Month 6 (502)	-2.3 (1.18)
Endpoint (859)	-2.0 (1.31)

14. Secondary Outcome

Title	Change From Baseline to 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. Baseline was the score before the first dose of study drug in the double-blind study.
Time Frame	Day 0 (baseline), Month 6 or the last post-baseline assessment)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	779
Mean (Standard Deviation) [units on a scale]	17.7 (13.61)

15. Primary 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. Baseline was the assessment before the first dose of study drug in the double-blind study.
Time Frame	Day 0 (baseline), Month 6 (or last post-baseline observation)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	855
Mean (Standard Deviation) [units on a scale]	-9.1 (7.66)

16. Primary 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. Baseline was the score before the first dose of study drug in the double-blind study.
Time Frame	Day 0 (baseline), Month 6 or last post-baseline observation

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
Measure Participants	786
Mean (Standard Deviation) [units on a scale]	-6.2 (5.68)

Adverse Events

Time Frame	Day 1 up to 6 months
Arm/Group Title	Armodafinil 150-200 mg/Day
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. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.
All Cause Mortality
	Armodafinil 150-200 mg/Day
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Armodafinil 150-200 mg/Day
	Affected / at Risk (%)	# Events
Total	27/863 (3.1%)
Cardiac disorders
Angina pectoris	1/863 (0.1%)	1
Myocardial infarction	1/863 (0.1%)	1
Torsade de pointes	1/863 (0.1%)	1
Gastrointestinal disorders
Colitis	1/863 (0.1%)	1
Diarrhoea	1/863 (0.1%)	1
Hepatobiliary disorders
Cholecystitis acute	1/863 (0.1%)	1
Infections and infestations
Laryngitis	1/863 (0.1%)	1
Pilonidal cyst	1/863 (0.1%)	1
Sialoadenitis	1/863 (0.1%)	1
Injury, poisoning and procedural complications
Accidental overdose	1/863 (0.1%)	1
Metabolism and nutrition disorders
Dehydration	1/863 (0.1%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/863 (0.1%)	1
Nervous system disorders
Transient ischaemic attack	1/863 (0.1%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/863 (0.1%)	1
Psychiatric disorders
Acute psychosis	1/863 (0.1%)	1
Agitation	1/863 (0.1%)	1
Alcohol abuse	1/863 (0.1%)	1
Alcohol withdrawal syndrome	1/863 (0.1%)	1
Bipolar I disorder	3/863 (0.3%)	3
Homicidal ideation	1/863 (0.1%)	1
Major depression	1/863 (0.1%)	1
Mania	5/863 (0.6%)	6
Suicidal ideation	3/863 (0.3%)	3
Suicide attempt	1/863 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/863 (0.1%)	1
Vascular disorders
Deep vein thrombosis	1/863 (0.1%)	1
Hypotension	1/863 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Armodafinil 150-200 mg/Day
	Affected / at Risk (%)	# Events
Total	133/863 (15.4%)
Nervous system disorders
Headache	96/863 (11.1%)	119
Psychiatric disorders
Insomnia	49/863 (5.7%)	56

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.