Extension Study of the Safety and Efficacy of Armodafinil in the Treatment of Patients With Excessive Sleepiness

• Sponsor: Cephalon (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00228553
• Collaborator: (none)
• Enrollment: 743
• Locations: 100
• Arm: 1
• Duration (Months): 26
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

A 12 Month, Open-Label, Flexible Dosage Extension Study of the Safety and Efficacy of Armodafinil (CEP-10953) in the Treatment of Patients with Excessive Sleepiness Associated with Narcolepsy, Obstructive Sleep Apnea/Hypopnea Syndrome, or Chronic Shift Work Sleep Disorder

Condition or Disease	Intervention/Treatment	Phase
Excessive Daytime Sleepiness; Narcolepsy; Obstructive Sleep Apnea/Hypopnea Syndrome; Chronic Shift Work Sleep Disorder	Drug: Armodafinil 100 to 250 mg/day	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 743 participants
• Allocation: Non-Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 12-Month, Open-Label, Flexible-Dosage (100 to 250 mg/Day) Extension Study of the Safety and Efficacy of Armodafinil (CEP-10953) in the Treatment of Patients With Excessive Sleepiness Associated With Narcolepsy, Obstructive Sleep Apnea/Hypopnea Syndrome, or Chronic Shift Work Sleep Disorder (With an Open-Ended Extension Period)
• Study Start Date: May 1, 2004
• Actual Study Completion Date: Jul 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Armodafinil 100 to 250 mg/day	Drug: Armodafinil 100 to 250 mg/day; Armodafinil 100-250 mg: once daily in the morning for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) or narcolepsy, once daily only on nights worked for patients with shift worker sleep disorder (SWSD).

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability in This Patient Population (Narcolepsy, OSAHS, SWSD) Over Time (up to 2 Years) [End of months 1, 3, 6, 9, and 12 and every 3 months for up to an additional year]

   An adverse event is any untoward medical occurrence in a patient that develops or worsens in severity during the conduct of a clinical study. Serious and Non-serious Adverse Events (SAEs). Serious adverse event is any adverse event occurring at any dose that results in any of the following outcomes: death, life-threatening, inpatient hospitalization, persistent or significant disability, congenital anomaly, or an important medical event. An adverse event that does not meet any of the criteria for seriousness listed previously will be regarded as a nonserious adverse event.

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:

• Men and women (outpatients) of any ethnic origin, between 18 and 65 years of age (inclusive) at the beginning of the respective double-blind study, are eligible.

• The patient has completed a cephalon-sponsored double-blind study (study C10953/3020/NA/MN, C10953/3021/AP/MN, C10953/3022/CM/MN, or C10953/3025/AP/MN), and the investigator has recommended they be enrolled.

• Patients with OSAHS must continue to be regular users of nCPAP therapy, which the investigator considers to remain effective. Patients with chronic SWSD must work 5 nights/month, with night shifts including at least 6 hours between 2200 and 0800 that are no longer than 12 hours in duration.

• The patient is considered to be in good health.

• Women must be surgically sterile, 2 years postmenopausal, or if of childbearing potential, must use a medically accepted method of birth control (ie, barrier method with spermicide, steroidal contraceptive [oral, implanted, and Depo-Provera contraceptives must be used in conjunction with a barrier method], or intrauterine device [IUD]).

• The patient must be 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:

• Have any clinically significant, uncontrolled medical conditions (treated or untreated).

• Have a probable diagnosis of a current sleep disorder other than the primary diagnosis of narcolepsy, OSAHS, or chronic SWSD.

• Consume caffeine including coffee, tea and/or other caffeine-containing beverages or food averaging more than 600 mg of caffeine.

• Use any prescription drugs disallowed by the protocol or clinically significant use of over-the-counter (OTC) drugs within 7 days before visit 1.

• Have a history of alcohol, narcotic, or any other drug abuse as defined by the Diagnostic and Statistical Manual of the American Psychiatric Association, 4th Edition (DSM-IV) (American Psychiatric Association 1994).

• Have a positive urine drug screen (UDS) (subjects enrolling in this open-label study within 7 days after completing the double-blind study may be enrolled without UDS results).

• Have a clinically significant deviation from normal in the physical examination.

• Are pregnant or lactating. Any woman becoming pregnant during the study will be withdrawn from the study.

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

• Have a known clinically significant drug sensitivity to stimulants.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sleep Disorders Ctr of Alabama	Birmingham	Alabama	United States	35213
2	Pulmonary Associates, PA	Phoenix	Arizona	United States	85006
3	Psypharma Clinical Research	Phoenix	Arizona	United States	85050
4	Central Arkansas Research	Hot Springs	Arkansas	United States	71913
5	Advanced Clinical Research Ins	Anaheim	California	United States	92801
6	Southwestern Research	Beverly Hills	California	United States	90210
7	Pacific Sleep Medicine Service	Los Angeles	California	United States	90048
8	Pacific Sleep Medicine Service	Palm Springs	California	United States	92262
9	Radiant Research San Diego	San Diego	California	United States	92103
10	Pacific Sleep Medicine Service	San Diego	California	United States	92121
11	BMR HealthQuest	San Diego	California	United States	92123
12	Sleep Clinic of San Francisco	San Francisco	California	United States	94117
13	St. Johns Medical Plaza Sleep	Santa Monica	California	United States	90404
14	Stanford University	Stanford	California	United States	94305
15	PAB Clinical Research	Brandon	Florida	United States	33511
16	St. Petersburg Sleep Disorder	St. Petersburg	Florida	United States	33707
17	Sleep-Wake Disorder Center	Winter Park	Florida	United States	32789
18	Neurotrials Research	Atlanta	Georgia	United States	30342
19	Sleep Disorders Center of GA	Atlanta	Georgia	United States	30342
20	SLEEPMED, Inc.	Macon	Georgia	United States	31202
21	Radiant Research Marietta	Marietta	Georgia	United States	30060
22	Henry Lahmeyer, MD	Northfield	Illinois	United States	60093
23	Peoria Pulmonary Associates	Peoria	Illinois	United States	61603
24	Center for Sleep Disorders	Danville	Indiana	United States	46122
25	University of Iowa Hospitals	Iowa City	Iowa	United States	52242
26	Vince and Associates Clinical	Overland Park	Kansas	United States	66211
27	Topeka Pulmonary	Topeka	Kansas	United States	66606
28	Graves Gilbert Clinic	Bowling Green	Kentucky	United States	42101
29	Community Research	Crestview	Kentucky	United States	45217
30	Chest Medicine Associates DBA	Louisville	Kentucky	United States	40217
31	Neurotrials Research of New Or	Metairie	Louisiana	United States	70001
32	Northshore Research Associates	Slidell	Louisiana	United States	70461
33	Center for Sleep/Wake Disorder	Chevy Chase	Maryland	United States	20815
34	Regional Pulmonary and Sleep	Elkton	Maryland	United States	21021
35	McLean Hospital	Belmont	Massachusetts	United States	02478
36	Neurocare, Inc.	Newton	Massachusetts	United States	02459
37	Sleep Disorders Center	Hattiesburg	Mississippi	United States	39404
38	Washington University School o	St. Louis	Missouri	United States	63105
39	Clinical Rsch Center of Nevada	Las Vegas	Nevada	United States	89104
40	CNS Research Institute	Clementon	New Jersey	United States	08021
41	Montefiore Medical Center	Bronx	New York	United States	10467
42	New York University	New York	New York	United States	10016
43	Clinilabs / Sleep Disorders In	New York	New York	United States	10025
44	Duke University Hospital	Durham	North Carolina	United States	27710
45	Vital re:Search	Greensboro	North Carolina	United States	27408
46	Neurology Associates of Hickor	Hickory	North Carolina	United States	28602
47	Wake Research Associates	Raleigh	North Carolina	United States	27612
48	Central Carolina Neurology Sle	Salisbury	North Carolina	United States	28144
49	All Trials Clinical Research	Winston-Salem	North Carolina	United States
50	St. Alexius Medical Center	Bismarck	North Dakota	United States	58501
51	North Coast Clinical Trials	Beechwood	Ohio	United States	44122
52	Community Research Management	Cincinnati	Ohio	United States	45219
53	Tri State Sleep Disorders Cent	Cincinnati	Ohio	United States	45246
54	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
55	Dept Veterans Affairs Dayton	Dayton	Ohio	United States	45428
56	Ohio Sleep Medicine-Neurosci	Dublin	Ohio	United States	43017
57	Southwest Cleveland Sleep Cent	Middleburg Heights	Ohio	United States	44130
58	St. Vincent Mercy Medical Cent	Toledo	Ohio	United States	43608
59	Clinical Pharmaceutical Trials	Tulsa	Oklahoma	United States	74104
60	Capital Region Sleep Disorders	Carlisle	Pennsylvania	United States	17013
61	Consolidated Clinical Trials	Pittsburgh	Pennsylvania	United States	15221
62	Omega Medical Research	Warwick	Rhode Island	United States	02886
63	Lowcountry Lung and Critical	Charleston	South Carolina	United States	29406
64	SleepMed of South Carolina	Columbia	South Carolina	United States	29201
65	St. Thomas Sleep Disorders Cen	Nashville	Tennessee	United States	37205
66	FutureSearch Trials	Austin	Texas	United States	78703
67	Sleep Medicine Institute	Dallas	Texas	United States
68	Houston Sleep Center	Houston	Texas	United States	77024
69	VA Medical CenterSleep Diagnos	Houston	Texas	United States	77030
70	Sadler Clinic	The Woodlands	Texas	United States	77380
71	Radiant Research Salt Lake	Salt Lake City	Utah	United States	84107
72	Sentara Norfolk General Hospit	Norfolk	Virginia	United States	23507
73	Swedish Sleep Medicine Institute	Seattle	Washington	United States	98122
74	Allegiance Research Specialist	Wauwatosa	Wisconsin	United States	53226
75	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia
76	St. George Hospital	Kogarah	New South Wales	Australia	2217
77	Westmead Hospital	Wentworthville	New South Wales	Australia
78	Monash Medical Center	Clayton	Victoria	Australia
79	Melbourne Sleep Disorders Ctr.	East Melbourne	Victoria	Australia
80	Canadian Sleep Institute	Calgary	Alberta	Canada
81	Sleep Clinic	Kitchener	Ontario	Canada	N2G1G1
82	Niagara Clinical Research	Niagara Falls	Ontario	Canada
83	Ottawa Hospital	Ottawa	Ontario	Canada	K1Y 4E9
84	West Parry Sound Health Center	Parry Sound	Ontario	Canada	P2A 1T3
85	Sleep and Neuropsychiatry Cent	Scarborough	Ontario	Canada
86	Toronto Western Hospital	Toronto	Ontario	Canada	M5T 2S8
87	Baycrest Hospital	Toronto	Ontario	Canada
88	Hopital Guy de Chauliac	Montpellier	Cedex 05	France	34295
89	Universitaires de Strasbourg	Strasbourg	Cedex	France	67091
90	Hopital Antoine Beclere	Clamart		France	92141
91	Hospital Henri-Mondor	Creteil		France	94010
92	University of Freiburg	Freiburg		Germany	D-79104
93	Klinikum der Philipps	Marburg		Germany	35033
94	University of Regensburg	Regensburg		Germany	D-93042
95	Hephata Klinik	Schwalmstadt		Germany	D-34613
96	SomniCare Sleep Institute	San Juan		Puerto Rico	00918
97	City Clinical Hospital 33	Moscow		Russian Federation
98	City Clinical Hospital 83	Moscow		Russian Federation
99	Clinical Hospital Russian Scie	Saint Petersburg		Russian Federation
100	Multifunction Center of Neurol	Samara		Russian Federation

Sponsors and Collaborators

• Cephalon

Investigators

• Study Director: Sponsor's Medical Director, MD, Cephalon

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00228553
• Other Study ID Numbers: C10953/3024/ES/MN
• First Posted: Sep 29, 2005
• Last Update Posted: Jul 19, 2013
• Last Verified: Jul 1, 2013

• Additional relevant MeSH terms: Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Sleep Wake Disorders; Parasomnias; Narcolepsy; Disorders of Excessive Somnolence; Sleep Disorders, Circadian Rhythm; Sleepiness; Modafinil

Study Results

Participant Flow

Recruitment Details	99 centers in the US, Canada, France, Germany, Russia, and Australia. First participant enrolled: 15 May 2004/ Last participant last visit: 19 July 2006
Pre-assignment Detail	12 participants (3 female ; 9 male) withdrew after randomization but prior to receiving study drug

Arm/Group Title	Armodafinil 100 to 250 mg/Day
Arm/Group Description	Armodafinil 100-250 mg: once daily in the morning for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) or narcolepsy, once daily only on nights worked for patients with shift worker sleep disorder (SWSD)
Period Title: Overall Study
STARTED	743
COMPLETED	313
NOT COMPLETED	430

Baseline Characteristics

Arm/Group Title	Armodafinil 100 to 250 mg/Day
Arm/Group Description	Armodafinil 100-250 mg: once daily in the morning for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) or narcolepsy, once daily only on nights worked for patients with shift worker sleep disorder (SWSD)
Overall Participants	731
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	726 99.3%
>=65 years	5 0.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.7 (10.97)
Sex: Female, Male (Count of Participants)
Female	257 35.2%
Male	474 64.8%
Region of Enrollment (participants) [Number]
France	8 1.1%
United States	611 83.6%
Canada	70 9.6%
Australia	25 3.4%
Russian Federation	16 2.2%
Germany	13 1.8%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability in This Patient Population (Narcolepsy, OSAHS, SWSD) Over Time (up to 2 Years)
Description	An adverse event is any untoward medical occurrence in a patient that develops or worsens in severity during the conduct of a clinical study. Serious and Non-serious Adverse Events (SAEs). Serious adverse event is any adverse event occurring at any dose that results in any of the following outcomes: death, life-threatening, inpatient hospitalization, persistent or significant disability, congenital anomaly, or an important medical event. An adverse event that does not meet any of the criteria for seriousness listed previously will be regarded as a nonserious adverse event.
Time Frame	End of months 1, 3, 6, 9, and 12 and every 3 months for up to an additional year

Outcome Measure Data

Analysis Population Description

Safety Analysis set of 731 total patients: 12 participants (3 female ; 9 male) withdrew after randomization but prior to receiving study drug.

Arm/Group Title	Armodafinil 100 to 250 mg/Day
Arm/Group Description	Armodafinil 100-250 mg: once daily in the morning for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) or narcolepsy, once daily only on nights worked for patients with shift worker sleep disorder (SWSD)
Measure Participants	731
Number [Participants]	667 91.2%

Adverse Events

Time Frame	For the duration of the study (up to 2 years)
Arm/Group Title	Armodafinil 100 to 250 mg/Day
Arm/Group Description	Armodafinil 100-250 mg: once daily in the morning for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) or narcolepsy, once daily only on nights worked for patients with shift worker sleep disorder (SWSD)
All Cause Mortality
	Armodafinil 100 to 250 mg/Day
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Armodafinil 100 to 250 mg/Day
	Affected / at Risk (%)	# Events
Total	56/731 (7.7%)
Cardiac disorders
Myocardial infarction	4/731 (0.5%)
Coronary artery disease	2/731 (0.3%)
Angina pectoris	1/731 (0.1%)
Atrial fibrillation	1/731 (0.1%)
Bradycardia	1/731 (0.1%)
Cardiac failure congestive	1/731 (0.1%)
Sinus bradycardia	1/731 (0.1%)
Supraventricular tachycardia	1/731 (0.1%)
Ventricular fibrillation	1/731 (0.1%)
Ventricular tachycardia	1/731 (0.1%)
Gastrointestinal disorders
Haemorrhoidal haemorrhage	2/731 (0.3%)
Abdominical adhesions	1/731 (0.1%)
Abdominal Hernia	1/731 (0.1%)
Diverticulitis	1/731 (0.1%)
Diverticulitis Intestinal	1/731 (0.1%)
Gastric Ulcer Haemorrhage	1/731 (0.1%)
Gastrooesophageal Reflux Disease	1/731 (0.1%)
Hiatus Hernia	1/731 (0.1%)
Intestinal Obstruction	1/731 (0.1%)
Pancreatitis	1/731 (0.1%)
Rectocele	1/731 (0.1%)
General disorders
Chest Pain	6/731 (0.8%)
Hepatobiliary disorders
Cholecystitis	1/731 (0.1%)
Cholecystitis Chronic	1/731 (0.1%)
Choletithiasis	1/731 (0.1%)
Infections and infestations
Cellulitis	2/731 (0.3%)
Appendicitis	1/731 (0.1%)
Bacteraemia	1/731 (0.1%)
Bursitis Infective	1/731 (0.1%)
Gastroenteritis	1/731 (0.1%)
Pnuemonia	1/731 (0.1%)
Pyelonephritis	1/731 (0.1%)
Injury, poisoning and procedural complications
Arthropod Bite	1/731 (0.1%)
Epicondylitis	1/731 (0.1%)
Heat Stroke	1/731 (0.1%)
Pelvic Fracture	1/731 (0.1%)
Rib Fracture	1/731 (0.1%)
Skin Laceration	1/731 (0.1%)
Tendon Rupture	1/731 (0.1%)
Investigations
Cardioactive Drug Level Increased	1/731 (0.1%)
Metabolism and nutrition disorders
Diabetes Mellitus	1/731 (0.1%)
Musculoskeletal and connective tissue disorders
Localised Osteoarthritis	1/731 (0.1%)
Tenosynovitis	1/731 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	2/731 (0.3%)
Chronic Myeloid Leukaemia	1/731 (0.1%)
Colon Cancer	1/731 (0.1%)
Gastric Cancer	1/731 (0.1%)
Non-Hodgkin's Lymphoma	1/731 (0.1%)
Parathyroid Tumour Benign	1/731 (0.1%)
Testis Cancer	1/731 (0.1%)
Nervous system disorders
Headache	1/731 (0.1%)
Intracranial Aneurysm	1/731 (0.1%)
Spinal Cord Compression	1/731 (0.1%)
Transient Ischaemic Attack	1/731 (0.1%)
Renal and urinary disorders
Nephrolithiasis	4/731 (0.5%)
Cystocele	1/731 (0.1%)
Renal Failure Acute	1/731 (0.1%)
Stress Incontinence	1/731 (0.1%)
Urethal Disorder	1/731 (0.1%)
Reproductive system and breast disorders
Adenomyosis	1/731 (0.1%)
Dysfunctional Uterine Bleeding	1/731 (0.1%)
Uterine Polyp	1/731 (0.1%)
Uterine Prolapse	1/731 (0.1%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/731 (0.1%)
Atelectasis	1/731 (0.1%)
Pneumothorax	1/731 (0.1%)
Pulmonary Embolism	1/731 (0.1%)
Pulmonary Oedema	1/731 (0.1%)
Vascular disorders
Hypertension	2/731 (0.3%)
Atherosclerosis	1/731 (0.1%)
Thrombosis	1/731 (0.1%)
Other (Not Including Serious) Adverse Events
	Armodafinil 100 to 250 mg/Day
	Affected / at Risk (%)	# Events
Total	667/731 (91.2%)
Gastrointestinal disorders
Nausea	68/731 (9.3%)
Dry mouth	49/731 (6.7%)
Diarrhoea	39/731 (5.3%)
Infections and infestations
Nasopharyngitis	123/731 (16.8%)
Upper respiratory tract infection	76/731 (10.4%)
Sinusitis	64/731 (8.8%)
Influenza	55/731 (7.5%)
Bronchitis	37/731 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	59/731 (8.1%)
Back pain	53/731 (7.3%)
Nervous system disorders
Headache	179/731 (24.5%)
Dizziness	47/731 (6.4%)
Psychiatric disorders
Insomnia	99/731 (13.5%)
Anxiety	57/731 (7.8%)
Respiratory, thoracic and mediastinal disorders
Cough	42/731 (5.7%)
Vascular disorders
Hypertension	40/731 (5.5%)

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.