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

This study has been completed.
Sponsor:
Information provided by:
Cephalon
ClinicalTrials.gov Identifier:
NCT00518986
First received: August 17, 2007
Last updated: March 28, 2011
Last verified: March 2011
History of Changes
Results First Received: March 30, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Sleep Disorders
Obstructive Sleep Apnea
Major Depressive Disorder
Dysthymic Disorder
Interventions: Drug: armodafinil
Drug: placebo

  Participant Flow
  Hide Participant Flow

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  
[1] One subject discontinued before treatment, only 124 subjects in each treatment group were dosed.



  Baseline Characteristics
  Hide Baseline Characteristics

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  



  Outcome Measures
  Show All Outcome Measures

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) ]
  Show Outcome Measure 1

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) ]
  Show Outcome Measure 2

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) ]
  Show Outcome Measure 3

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

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 ]
  Show Outcome Measure 5

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) ]
  Show Outcome Measure 6

7.  Secondary:   Clinical Global Impression of Change (CGI-C) at 4 Weeks   [ Time Frame: 4 weeks after beginning study drug treatment ]
  Show Outcome Measure 7

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

9.  Secondary:   Clinical Global Impression of Change (CGI-C) at 12 Weeks   [ Time Frame: 12 weeks after beginning treatment ]
  Show Outcome Measure 9

10.  Secondary:   Clinical Global Impression of Change (CGI C) at 4 Weeks - Full Scale   [ Time Frame: 4 weeks after start of treatment ]
  Show Outcome Measure 10

11.  Secondary:   Clinical Global Impression of Change (CGI-C) at 8 Weeks - Full Scale   [ Time Frame: 8 weeks after start of study drug treatment ]
  Show Outcome Measure 11

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

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 ]
  Show Outcome Measure 13

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 ]
  Show Outcome Measure 14

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 ]
  Show Outcome Measure 15

16.  Secondary:   Change From Baseline on Epworth Sleepiness Scale (ESS) at 12 Weeks   [ Time Frame: 12 weeks (or last observation after baseline) ]
  Show Outcome Measure 16

17.  Secondary:   Number of Responders According to the Epworth Sleepiness Scale (ESS) Total Score at 2 Weeks   [ Time Frame: 2 weeks ]
  Show Outcome Measure 17

18.  Secondary:   Number of Responders According to the Epworth Sleepiness Scale (ESS) Total Score at 4 Weeks   [ Time Frame: 4 weeks ]
  Show Outcome Measure 18

19.  Secondary:   Number of Responders According to the Epworth Sleepiness Scale (ESS) Total Score at 8 Weeks   [ Time Frame: 8 weeks ]
  Show Outcome Measure 19

20.  Secondary:   Number of Responders According to the Epworth Sleepiness Scale (ESS) Total Score at 12 Weeks   [ Time Frame: 12 weeks ]
  Show Outcome Measure 20

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 ]
  Show Outcome Measure 21

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 ]
  Show Outcome Measure 22

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 ]
  Show Outcome Measure 23

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 ]
  Show Outcome Measure 24

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 ]
  Show Outcome Measure 25

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 ]
  Show Outcome Measure 26

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 ]
  Show Outcome Measure 27

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 ]
  Show Outcome Measure 28

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 ]
  Show Outcome Measure 29

30.  Secondary:   Change From Baseline on Brief Fatigue Inventory (BFI) Worse Daily Fatigue Score at 12 Weeks   [ Time Frame: 12 weeks ]
  Show Outcome Measure 30

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) ]
  Show Outcome Measure 31

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 ]
  Show Outcome Measure 32

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 ]
  Show Outcome Measure 33

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 ]
  Show Outcome Measure 34

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 ]
  Show Outcome Measure 35

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) ]
  Show Outcome Measure 36

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 ]
  Show Outcome Measure 37

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 ]
  Show Outcome Measure 38

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 ]
  Show Outcome Measure 39

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 ]
  Show Outcome Measure 40

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) ]
  Show Outcome Measure 41

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 ]
  Show Outcome Measure 42

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 ]
  Show Outcome Measure 43

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 ]
  Show Outcome Measure 44

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 ]
  Show Outcome Measure 45

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) ]
  Show Outcome Measure 46

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 ]
  Show Outcome Measure 47

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 ]
  Show Outcome Measure 48

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 ]
  Show Outcome Measure 49

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 ]
  Show Outcome Measure 50

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) ]
  Show Outcome Measure 51

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 ]
  Hide Outcome Measure 52

Measure Type Secondary
Measure Title Change From Baseline on Medical Outcomes Study 6 Item Cognitive Functioning (MOS-CF6) Scale at 2 Weeks
Measure Description The MOS-CF6 assesses self-reported cognitive function. Items were selected to cover 6 relevant aspects of cognitive functioning as follows: confusion, concentration/thinking, attention, memory, reasoning, problem-solving, and processing speed. The MOS-CF6 responses includes 6 choices, ranging from "none of the time" to "all of the time". The MOS-CF6 is scored by summing responses across the 6 items and converting the total to a 0 - 100 point scale, with the higher score indicating better cognitive functioning. Data is presented showing the change in score from baseline to 2 weeks.
Time Frame baseline and 2 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set defined as subjects who completed the MOS-CF6 at baseline and at 2 weeks

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.

Measured Values
    Armodafinil 200 mg/Day     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  109     104  
Change From Baseline on Medical Outcomes Study 6 Item Cognitive Functioning (MOS-CF6) Scale at 2 Weeks  
[units: Units on a scale]
Least Squares Mean ± Standard Error 		  2.0  ± 0.57     1.9  ± 0.58  


Statistical Analysis 1 for Change From Baseline on Medical Outcomes Study 6 Item Cognitive Functioning (MOS-CF6) Scale at 2 Weeks
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.8930
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Least square (LS) mean and standard error of the LS mean for each treatment group, and the p-value for the treatment comparison is from an analysis of covariance (ANCOVA) with treatment as a factor and the baseline value as a covariate.
[2] Other relevant information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



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 ]
  Show Outcome Measure 53

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 ]
  Show Outcome Measure 54

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 ]
  Show Outcome Measure 55

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) ]
  Show Outcome Measure 56

57.  Secondary:   Change From Baseline in the Excessive Sleepiness (ES) Symptom Rating Form - Sleepiness Scores at 2 Weeks   [ Time Frame: Baseline and 2 weeks ]
  Show Outcome Measure 57

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 ]
  Show Outcome Measure 58

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 ]
  Show Outcome Measure 59

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 ]
  Show Outcome Measure 60


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Medical monitor
Organization: Cephalon, Inc.
phone: 1-800-896-5855


No publications provided by Cephalon

Publications automatically indexed to this study:


Responsible Party: Sponsor's Medical Expert, Cephalon
ClinicalTrials.gov Identifier: NCT00518986     History of Changes
Other Study ID Numbers: C10953/4024/ES/US
Study First Received: August 17, 2007
Results First Received: March 30, 2010
Last Updated: March 28, 2011
Health Authority: United States: Food and Drug Administration