Safety/Efficacy Study With Armodafinil (CEP-10953) in Treatment of Excessive Sleepiness Associated With Chronic SWSD

• Sponsor: Cephalon (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00080288
• Collaborator: (none)
• Enrollment: 254
• Arms: 2
• Duration (Months): 9

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine whether treatment with Armodafinil (CEP-10953) is more effective than placebo treatment for patients with excessive sleepiness associated with chronic shift work sleep disorder (SWSD) by measuring mean sleep latency from the Multiple Sleep Latency Test (MSLT) (20 minutes) (average of 4 naps at 0200, 0400, 0600, and 0800) and by Clinical Global Impression of Change (CGI-C) ratings.

Condition or Disease	Intervention/Treatment	Phase
Excessive Sleepiness; Shift Work Sleep Disorder	Drug: Armodafinil 150 mg/day; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 254 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A 12 Week, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of CEP 10953 (150 mg) as Treatment for Adults With Excessive Sleepiness Associated With Chronic Shift Work Sleep Disorder
• Study Start Date: Mar 1, 2004
• Study Completion Date: Dec 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Armodafinil 150 mg/day	Drug: Armodafinil 150 mg/day; Armodafinil 150 mg taken 30 minutes to 1 hour before the start of the night shift, but no later than 2300, only on nights worked.
Placebo Comparator: 2 Placebo	Drug: Placebo; Matching placebo tablets once daily

Outcome Measures

Primary Outcome Measures

1. Multiple Sleep Latency Test (MSLT) [up to 12 weeks]

   The Multiple Sleep Latency Test (MSLT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. Mean sleep latency from MSLT was measured for five 20-minute (maximum) MSLT naps performed at scheduled visits (2400 [midnight], 0200, 0400, 0600, and 0800).The MSLT was administered at weeks 4, 8, and 12. The primary efficacy variable was the mean change from the baseline assessment in MSLT sleep latency as assessed at week 12 (or last postbaseline visit).

2. Clinical Global Impression of Change (CGI-C) [up to 12 weeks]

   Number of participants who had at least minimal improvement in CGI-C ratings at Week 12 or last post-baseline visit. The CGI-C uses the following categories and scoring assignments: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; and 7=Very much worse. Severity of illness was assessed at baseline by the CGI-S, which consists of the following categories: 1=Normal (shows no signs of illness); 2=Borderline ill; 3=Mildly (Slightly) ill; 4=Moderately ill; 5=Markedly ill; 6=Severely ill; and 7=Among the most extremely ill patients.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Patients are included in the study if all of the following criteria are met:

• Written informed consent is obtained.

• The patient is an outpatient, man or woman of any ethnic origin, 18 to 65 years of age (inclusive).

• The patient has a complaint of excessive sleepiness.

• The patient has a diagnosis of SWSD according to International Classification of Sleep Disorders (ICSD) criteria, and must have had excessive sleepiness during night shifts for at least 3 months.

• The patient must work at least 5 night shifts per month, of which at least 3 nights are consecutive, and plan to maintain this schedule.

• The patient must work night shifts that include at least 6 hours between 2200 and 0800 and be no longer than 12 hours in duration.

• The patient is in good health as determined by a medical and psychiatric history, physical examination, ECG, and serum chemistry and hematology.

• Women must be surgically sterile, 2 years postmenopausal, or, if of child-bearing potential, using a medically accepted method of birth control (ie, barrier method with spermicide, steroidal contraceptive, or intrauterine device [IUD]) and agree to continued use of this method for the duration of the study. Steroidal contraceptives must be used with a barrier method while taking the study drug and for at least a full cycle after discontinuation of the study drug.

• The patient has a mean sleep latency of 6 minutes or less as determined by the MSLT

• The patient has a CGI-S rating as it pertains to sleepiness during night shifts including the commute to and from work.

• The patient does not have any medical or psychiatric disorders that could account for the excessive sleepiness during the night shift.

• The patient is able to complete self rating scales and computer-based testing.

• The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.

Exclusion Criteria:

Patients are excluded from participating in this study if 1 or more of the following criteria are met:

• has any clinically significant, uncontrolled medical or psychiatric conditions (treated or untreated)

• has a probable diagnosis of a current sleep disorder other than SWSD

• consumes caffeine including coffee, tea and/or other caffeine containing beverages or food averaging more than 600 mg of caffeine per day

• used any prescription drugs disallowed by the protocol or clinically significant use of over the-counter (OTC) drugs within 7 days before the screening/baseline visit

• has a history of alcohol, narcotic, or any other drug abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, 4th Edition (DSM IV)

• has a positive urine drug screen (UDS) at the screening visit

• has a clinically significant deviation from normal in the physical examination

• is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.)

• has used an investigational drug within 1 month before the screening visit

• has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery)

• has a known clinically significant drug sensitivity to stimulants or modafinil

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Cephalon

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00080288
• Other Study ID Numbers: C10953/3022/CM/MN
• First Posted: Mar 29, 2004
• Last Update Posted: Jul 19, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by , ,: Excessive Sleepiness; Chronic Shift Work Sleep Disorder; Chronic SWSD; Circadian Rhythm Disorder; Shift Worker; Cephalon; Cephalon, Inc; Nuvigil
• Additional relevant MeSH terms: Sleep Wake Disorders; Parasomnias; Disorders of Excessive Somnolence; Sleep Disorders, Circadian Rhythm; Sleepiness; Modafinil

Study Results

Participant Flow

Recruitment Details	42 centers (37 in US, 5 in Canada). First patient enrolled: 2 April 2004/ Last patient last visit: 23 December 2004
Pre-assignment Detail	9 participants (3 female ; 6 male) withdrew after randomization but prior to receiving study drug. These 9 patients are included in the Participant Flow table below.

Arm/Group Title	Armodafinil 150 mg/Day	Placebo
Arm/Group Description	Armodafinil 150 mg taken 30 minutes to 1 hour before the start of the night shift, but no later than 2300, only on nights worked	Matching placebo tablets once daily
Period Title: Overall Study
STARTED	127	127
COMPLETED	97	89
NOT COMPLETED	30	38

Baseline Characteristics

Arm/Group Title	Armodafinil 150 mg/Day	Placebo	Total
Arm/Group Description	Armodafinil 150 mg taken 30 minutes to 1 hour before the start of the night shift, but no later than 2300, only on nights worked	Matching placebo tablets once daily	Total of all reporting groups
Overall Participants	127	127	254
Age (participants) [Number]
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	123 96.9%	122 96.1%	245 96.5%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.9 (10.75)	40.3 (10.76)	39.6 (10.76)
Gender (participants) [Number]
Female	57 44.9%	58 45.7%	115 45.3%
Male	66 52%	64 50.4%	130 51.2%
Region of Enrollment (participants) [Number]
United States	117 92.1%	117 92.1%	234 92.1%
Canada	10 7.9%	10 7.9%	20 7.9%

Outcome Measures

1. Primary Outcome

Title	Multiple Sleep Latency Test (MSLT)
Description	The Multiple Sleep Latency Test (MSLT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. Mean sleep latency from MSLT was measured for five 20-minute (maximum) MSLT naps performed at scheduled visits (2400 [midnight], 0200, 0400, 0600, and 0800).The MSLT was administered at weeks 4, 8, and 12. The primary efficacy variable was the mean change from the baseline assessment in MSLT sleep latency as assessed at week 12 (or last postbaseline visit).
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis set of 245 total patients: 9 participants withdrew after randomization but prior to receiving study drug Full Analysis set of 216 total patients: 29 patients that had withdrawn from the study were non-evaluable for efficacy.

Arm/Group Title	Armodafinil 150 mg/Day	Placebo
Arm/Group Description	Armodafinil 150 mg taken 30 minutes to 1 hour before the start of the night shift, but no later than 2300, only on nights worked	Matching placebo tablets once daily
Measure Participants	112	104
Mean (Standard Deviation) [Minutes]	3.1 (4.46)	0.4 (2.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Armodafinil 150 mg/Day, Placebo
	Comments	Assumption: both primary treatment comparisons would be with a 2 sided test at an alpha level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.7
	Confidence Interval	() 95%; 1.67 to 3.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Clinical Global Impression of Change (CGI-C)
Description	Number of participants who had at least minimal improvement in CGI-C ratings at Week 12 or last post-baseline visit. The CGI-C uses the following categories and scoring assignments: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; and 7=Very much worse. Severity of illness was assessed at baseline by the CGI-S, which consists of the following categories: 1=Normal (shows no signs of illness); 2=Borderline ill; 3=Mildly (Slightly) ill; 4=Moderately ill; 5=Markedly ill; 6=Severely ill; and 7=Among the most extremely ill patients.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis set of 245 total patients: 9 participants withdrew after randomization but prior to receiving study drug Full Analysis set of 216 total patients: 29 patients that had withdrawn from the study were non-evaluable for efficacy.

Arm/Group Title	Armodafinil 150 mg/Day	Placebo
Arm/Group Description	Armodafinil 150 mg taken 30 minutes to 1 hour before the start of the night shift, but no later than 2300, only on nights worked	Matching placebo tablets once daily
Measure Participants	112	104
Number [Participants]	112 88.2%	104 81.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Armodafinil 150 mg/Day, Placebo
	Comments	Assumption: both primary treatment comparisons would be with a 2 sided test at an alpha level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	The p value for each treatment group is for the comparison of that treatment group to the placebo treatment group. Adjusted for country.

Adverse Events

Arm/Group Title	Armodafinil 150 mg/Day		Placebo
Arm/Group Description	Armodafinil 150 mg taken 30 minutes to 1 hour before the start of the night shift, but no later than 2300, only on nights worked		Matching placebo tablets once daily
All Cause Mortality
	Armodafinil 150 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Armodafinil 150 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/123 (0.8%)		1/122 (0.8%)
Infections and infestations
Meningitis viral	1/123 (0.8%)		0/122 (0%)
Psychiatric disorders
Depression suicidal	0/123 (0%)		1/122 (0.8%)
Other (Not Including Serious) Adverse Events
	Armodafinil 150 mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/123 (22.8%)		18/122 (14.8%)
Gastrointestinal disorders
Nausea	9/123 (7.3%)		4/122 (3.3%)
Infections and infestations
Nasopharyngitis	7/123 (5.7%)		4/122 (3.3%)
Nervous system disorders
Headache	15/123 (12.2%)		12/122 (9.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.