Efficacy and Safety of Armodafinil for Adults With Excessive Sleepiness Obstructive Sleep Apnea/Hypopnea and Depression

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
55 centers in the US. First participant enrolled: October 2007/ Last participant last visit: March 2009

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study consisted of a 1-week single-blind, placebo run-in screening period followed by a 12-week double blind treatment period. Of the 249 patients enrolled, 248 patients received at least 1 dose of study drug and were evaluated for safety; 1 patient who was assigned to receive armodafinil was lost to follow-up before taking any study drug.

Reporting Groups

	Description
Armodafinil 200 mg/Day	Armodafinil (or placebo) was titrated to a target dosage of 200 mg/day (4 tablets) for each patient. Dosing began at 50 mg (1 tablet)/day each morning on Day 1, and then increased by 50 mg (1 tablet) on days 2, 5, and 8 to target dose of 200 mg/day (4 tablets). If deemed appropriate by investigator, dose could be further titrated to 250 mg/day (5 tablets). If tolerability issues arose, dose could be decreased in 50 mg increments anytime after 200 mg/day dose was achieved.
Placebo	Placebo tablets matching the 50 mg armodafinil tablet were used in a manner identical to that of the armodafinil tablets for both the placebo run in period and the double blind treatment period. Study drug was titrated to a target dosage of 4 tablets/day for each patient. Dosing began at 1 tablet/day in the morning on Day 1, and then increased by 1 tablet on days 2, 5, and 8 to target dose of 4 tablets. If deemed appropriate by investigator, dose could be further titrated to 5 tablets. If tolerability issues arose, dose could be decreased in 1 tablet increments anytime after 4 tablets/day dose was achieved.

Participant Flow:   Overall Study

	Armodafinil 200 mg/Day	Placebo
STARTED	125 [1]	124
COMPLETED	99	98
NOT COMPLETED	26	26
Adverse Event	12	7
Lack of Efficacy	0	2
Lost to Follow-up	3	2
Physician Decision	0	3
Protocol Violation	5	7
Withdrawal by Subject	4	4
Non-Specific	2	1

Reporting Groups

	Description
Armodafinil 200 mg/Day	Armodafinil (or placebo) was titrated to a target dosage of 200 mg/day (4 tablets) for each patient. Dosing began at 50 mg (1 tablet)/day each morning on Day 1, and then increased by 50 mg (1 tablet) on days 2, 5, and 8 to target dose of 200 mg/day (4 tablets). If deemed appropriate by investigator, dose could be further titrated to 250 mg/day (5 tablets). If tolerability issues arose, dose could be decreased in 50 mg increments anytime after 200 mg/day dose was achieved.
Placebo	Placebo tablets matching the 50 mg armodafinil tablet were used in a manner identical to that of the armodafinil tablets for both the placebo run in period and the double blind treatment period. Study drug was titrated to a target dosage of 4 tablets/day for each patient. Dosing began at 1 tablet/day in the morning on Day 1, and then increased by 1 tablet on days 2, 5, and 8 to target dose of 4 tablets. If deemed appropriate by investigator, dose could be further titrated to 5 tablets. If tolerability issues arose, dose could be decreased in 1 tablet increments anytime after 4 tablets/day dose was achieved.
Total	Total of all reporting groups

Baseline Measures

	Armodafinil 200 mg/Day	Placebo	Total
Number of Participants   [units: participants]	125	124	249
Age   [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	125	124	249
>=65 years	0	0	0
Age   [units: years] Mean ± Standard Deviation	49.5  ± 10.32	49.5  ± 9.69	49.5  ± 9.99
Gender   [units: participants]
Female	68	66	134
Male	57	58	115
Region of Enrollment   [units: participants]
United States	125	124	249

1.  Primary:

Change From Baseline on Maintenance of Wakefulness Test (MWT) to Endpoint (12 Weeks or Last Observation After Baseline)   [ Time Frame: Baseline and 12 weeks (or last observation after baseline) ]

2.  Primary:

Clinical Global Impression of Change (CGI-C) at Endpoint (12-weeks or Last Observation After Baseline)   [ Time Frame: 12 weeks (or last observation after baseline) ]

3.  Secondary:

Change From Baseline on the Epworth Sleepiness Scale (ESS) at Endpoint (12 Weeks or Last Measurement After Baseline)   [ Time Frame: Baseline and 12 weeks (or last observation after baseline) ]

4.  Secondary:

Change From Baseline on Maintenance of Wakefulness Test (MWT) at 4 Weeks   [ Time Frame: baseline and 4 weeks ]

5.  Secondary:

Change From Baseline on Maintenance of Wakefulness Test (MWT) at 8 Weeks   [ Time Frame: Baseline and 8 weeks following start of study drug administration ]

6.  Secondary:

Change From Baseline on Maintenance of Wakefulness Test (MWT) at 12 Weeks   [ Time Frame: baseline and 12 weeks (or last observation after baseline) ]

7.  Secondary:

Clinical Global Impression of Change (CGI-C) at 4 Weeks   [ Time Frame: 4 weeks after beginning study drug treatment ]

8.  Secondary:

Clinical Global Impression of Change (CGI-C) at 8 Weeks   [ Time Frame: 8 weeks after beginning study drug treatment ]

9.  Secondary:

Clinical Global Impression of Change (CGI-C) at 12 Weeks   [ Time Frame: 12 weeks after beginning treatment ]

10.  Secondary:

Clinical Global Impression of Change (CGI C) at 4 Weeks - Full Scale   [ Time Frame: 4 weeks after start of treatment ]

11.  Secondary:

Clinical Global Impression of Change (CGI-C) at 8 Weeks - Full Scale   [ Time Frame: 8 weeks after start of study drug treatment ]

12.  Secondary:

Clinical Global Impression of Change (CGI-C) at 12 Weeks - Full Scale   [ Time Frame: 12 weeks after starting study drug treatment ]

13.  Secondary:

Change From Baseline on Epworth Sleepiness Scale (ESS) at 2 Weeks   [ Time Frame: Baseline and 2 weeks following start of study drug administration ]

14.  Secondary:

Change From Baseline on Epworth Sleepiness Scale (ESS) at 4 Weeks   [ Time Frame: Baseline and 4 weeks after start of study drug administration ]

15.  Secondary:

Change From Baseline on Epworth Sleepiness Scale (ESS) at 8 Weeks   [ Time Frame: Baseline and 8 weeks after start of study drug administration ]

16.  Secondary:

Change From Baseline on Epworth Sleepiness Scale (ESS) at 12 Weeks   [ Time Frame: 12 weeks (or last observation after baseline) ]

17.  Secondary:

Number of Responders According to the Epworth Sleepiness Scale (ESS) Total Score at 2 Weeks   [ Time Frame: 2 weeks ]

18.  Secondary:

Number of Responders According to the Epworth Sleepiness Scale (ESS) Total Score at 4 Weeks   [ Time Frame: 4 weeks ]

19.  Secondary:

Number of Responders According to the Epworth Sleepiness Scale (ESS) Total Score at 8 Weeks   [ Time Frame: 8 weeks ]

20.  Secondary:

Number of Responders According to the Epworth Sleepiness Scale (ESS) Total Score at 12 Weeks   [ Time Frame: 12 weeks ]

21.  Secondary:

Change From Baseline to Endpoint (Week 12 or Last Observation After Baseline) in the Brief Fatigue Inventory (BFI) Total Score   [ Time Frame: Baseline and 12 weeks following start of study drug administration or last recorded observation ]

22.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Total Score at 2 Weeks   [ Time Frame: Baseline and 2 weeks after start of study drug administration ]

23.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Total Score at 4 Weeks   [ Time Frame: Baseline and 4 weeks after start of study drug administration ]

24.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Total Score at 8 Weeks   [ Time Frame: Baseline and 8 weeks after start of study drug administration ]

25.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Total Score at 12 Weeks   [ Time Frame: Baseline and 12 weeks after start of study drug administration ]

26.  Secondary:

Change From Baseline on the Brief Fatigue Inventory (BFI) Worst Daily Fatigue Score at Endpoint (12 Weeks or Last Observation After Baseline)   [ Time Frame: Baseline and 12 weeks or last observation after baseline ]

27.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Worse Daily Fatigue Score at 2 Weeks   [ Time Frame: Baseline and 2 weeks after start of study drug administration ]

28.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Worse Daily Fatigue Score at 4 Weeks   [ Time Frame: Baseline and 4 weeks after start of study drug administration ]

29.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Worse Daily Fatigue Score at 8 Weeks   [ Time Frame: Baseline and 8 weeks after start of study drug administration ]

30.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Worse Daily Fatigue Score at 12 Weeks   [ Time Frame: 12 weeks ]

31.  Secondary:

Number of Responders According to Brief Fatigue Inventory (BFI) Worst Fatigue Score at Endpoint (12 Weeks or Last Observation After Baseline)   [ Time Frame: 12 weeks after start of study drug administration (or last observation after baseline) ]

32.  Secondary:

Number of Responders According to the Brief Fatigue Inventory (BFI) Worst Fatigue Score at 2 Weeks   [ Time Frame: 2 weeks after start of study drug administration ]

33.  Secondary:

Number of Responders According to the Brief Fatigue Inventory (BFI) Worst Fatigue Score at 4 Weeks   [ Time Frame: 4 weeks after start of study drug administration ]

34.  Secondary:

Number of Responders According to the Brief Fatigue Inventory (BFI) Worst Fatigue Score at 8 Weeks   [ Time Frame: 8 weeks after start of study drug administration ]

35.  Secondary:

Number of Responders According to the Brief Fatigue Inventory (BFI) Worst Fatigue Score at 12 Weeks   [ Time Frame: 12 weeks after start of study drug administration ]

36.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Interference Score at Endpoint (12 Weeks or Last Observation After Baseline)   [ Time Frame: Baseline and at endpoint (12 weeks or last observation after baseline) ]

37.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Interference Score at 2 Weeks   [ Time Frame: Baseline and 2 weeks after start of study drug administration ]

38.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Interference Score at 4 Weeks   [ Time Frame: Baseline and 4 weeks after start of study drug administration ]

39.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Interference Score at 8 Weeks   [ Time Frame: Baseline and 8 weeks after start of study drug administration ]

40.  Secondary:

Change From Baseline on Brief Fatigue Inventory (BFI) Interference Score at 12 Weeks (or Last Observation After Baseline)   [ Time Frame: Baseline and 12 weeks after start of study drug administration ]

41.  Secondary:

Change From Baseline on Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score at Endpoint (12 Weeks or Last Observation After Baseline)   [ Time Frame: Baseline and endpoint (12 weeks after start of study drug or last observation after baseline) ]

42.  Secondary:

Change From Baseline on Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score at 2 Weeks   [ Time Frame: baseline and 2 weeks following start of study drug administration ]

43.  Secondary:

Change From Baseline on Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score at 4 Weeks   [ Time Frame: baseline and 4 weeks following start of study drug administration ]

44.  Secondary:

Change From Baseline on Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score at 8 Weeks   [ Time Frame: baseline and 8 weeks following start of study drug administration ]

45.  Secondary:

Change From Baseline on Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score at 12 Weeks   [ Time Frame: baseline and 12 weeks following the start of study drug administration ]

46.  Secondary:

Number of Responders According to the Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score at Endpoint (Week 12 or Last Observation After Baseline)   [ Time Frame: Endpoint (week 12 or last observation after baseline) ]

47.  Secondary:

Number of Responders According to the Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score at 2 Weeks   [ Time Frame: 2 weeks following start of study drug administration ]

48.  Secondary:

Number of Responders According to the Functional Outcomes of Sleep Questionnaire (FOSQ) at Week 4   [ Time Frame: 4 weeks following start of study drug administration ]

49.  Secondary:

Number of Responders According to the Functional Outcomes of Sleep Questionnaire (FOSQ) at Week 8   [ Time Frame: 8 weeks following start of study drug administration ]

50.  Secondary:

Number of Responders According to the Functional Outcomes of Sleep Questionnaire (FOSQ) at Week 12   [ Time Frame: 12 weeks following the start of study drug administration ]

51.  Secondary:

Change From Baseline on Medical Outcomes Study 6 Item Cognitive Functioning (MOS-CF6) Scale at Endpoint (12 Weeks or Last Observation After Baseline)   [ Time Frame: Baseline and Endpoint (12 weeks or last observation after baseline) ]

52.  Secondary:

Change From Baseline on Medical Outcomes Study 6 Item Cognitive Functioning (MOS-CF6) Scale at 2 Weeks   [ Time Frame: baseline and 2 weeks ]

53.  Secondary:

Change From Baseline on Medical Outcomes Study 6 Item Cognitive Functioning (MOS-CF6) Scale at 4 Weeks   [ Time Frame: baseline and 4 weeks following start of study drug administration ]

54.  Secondary:

Change From Baseline on Medical Outcomes Study 6 Item Cognitive Functioning (MOS-CF6) Scale at 8 Weeks   [ Time Frame: baseline and 8 weeks following start of study drug administration ]

55.  Secondary:

Change From Baseline on Medical Outcomes Study 6 Item Cognitive Functioning (MOS-CF6) Scale at 12 Weeks   [ Time Frame: baseline and 12 weeks following start of study drug administration ]

56.  Secondary:

Change From Baseline in the Excessive Sleepiness (ES) Symptom Rating Form - Sleepiness Scores at Endpoint (12 Weeks or Last Observation After Baseline)   [ Time Frame: Baseline and Endpoint (12 weeks or last observation after baseline) ]

57.  Secondary:

Change From Baseline in the Excessive Sleepiness (ES) Symptom Rating Form - Sleepiness Scores at 2 Weeks   [ Time Frame: Baseline and 2 weeks ]

58.  Secondary:

Change From Baseline in the Excessive Sleepiness (ES) Symptom Rating Form - Sleepiness Scores at 4 Weeks   [ Time Frame: Baseline and 4 weeks following start of study drug administration ]

59.  Secondary:

Change From Baseline in the Excessive Sleepiness (ES) Symptom Rating Form - Sleepiness Scores at 8 Weeks   [ Time Frame: baseline and 8 weeks following start of study drug administration ]

60.  Secondary:

Change From Baseline in the Excessive Sleepiness (ES) Symptom Rating Form - Sleepiness Scores at 12 Weeks   [ Time Frame: Baseline and 12 weeks following start of study drug administration ]