Study to Evaluate the Efficacy and Safety of Armodafinil as Treatment for Patients With Excessive Sleepiness Associated With Mild or Moderate Closed Traumatic Brain Injury

NCT00893789 | Terminated Phase 3 Results

• 1 other identifier: C10953/3067/ES/MN
• Study Type: interventional
• Target: 117
• Locations: 4 countries
• Sites: 73

Brief Summary

The primary objective of the study is to determine whether armodafinil treatment is more effective than placebo treatment in patients with excessive sleepiness associated with mild or moderate closed traumatic brain injury (TBI).

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Multiple Sleep Latency Test (MSLT) at Endpoint (Last Postbaseline Observation Up to Week 12)

  The MSLT is an objective assessment of sleepiness that measures the likelihood of falling asleep. Four 20-minute (maximum) MSLT naps were performed at 0900, 1100, 1300, and 1500. The participant, dressed in nonconstricting clothes, was instructed to lie quietly and attempt sleep. Each MSLT nap continued until: (a) 3 consecutive 30-second epochs of stage 1 sleep were reached or (b) any single, 30-second epoch of stage 2, 3, 4, or rapid eye movement (REM) sleep was reached. Sleep latency for each nap and average sleep latency for the 4 naps were tabulated. According to clinical protocol for the MSLT, each nap was terminated after 20 minutes if no sleep occurred. If a participant did not fall asleep in 20 minutes, his/her sleep latency for that nap was set to 20 minutes. Sleep latency was measured as the elapsed time from lights-out to the first epoch scored as sleep. With a 30-second scoring epoch, this criterion was reached when sleep occupied at least 16 seconds of any epoch.

  Baseline, last postbaseline observation up to Week 12

• Percentage of Responders and Nonresponders According to Clinical Global Impression of Change (CGI-C) Ratings at Endpoint (Last Postbaseline Observation Up to Week 12)

  The CGI-C is the clinician's rating of disease severity as compared with pretreatment, assessed by the Clinical Global Impression of Severity (CGI-S). Severity of illness, as related to excessive sleepiness, was assessed at baseline by the CGI-S, which consists of 7 categories: normal-shows no sign of illness, borderline ill, mildly (slightly) ill, moderately ill, markedly ill, severely ill, and among the most extremely ill. The clinician assessed the change from baseline in the participant's condition, as related to excessive sleepiness, in response to treatment. The CGI-C uses the following 7 categories and scoring assignments: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse. Responders were defined as those participants who were considered much or very much improved on the CGI-C. Those in all other categories of the CGI-C were considered nonresponders.

  Last postbaseline observation up to Week 12

Secondary Outcomes (17)

• Change From Baseline in Mean Sleep Latency From the MSLT at Weeks 4, 8, and 12

  Baseline, Weeks 4, 8, and 12

• Percentage of Responders and Nonresponders According to Clinical Global Impression of Change (CGI-C) Ratings at Weeks 2, 4, 8, and 12

  Weeks 2, 4, 8, and 12

• Change From Baseline in Traumatic Brain Injury - Work Instability Scale (TBI-WIS) Total Score At Weeks 4, 8, 12 and Endpoint (Last Postbaseline Observation Up to Week 12)

  Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12)

• Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 12 and Endpoint (Last Postbaseline Observation Up to Week 12)

  Baseline, Week 12, Endpoint (last postbaseline observation, up to Week 12)

• Percentage of Participants Answering "No" to All Questions on the Columbia-Suicide Severity Rating Scale Since Last Visit Version (C-SSRS SLV) at Weeks 2, 4, 8, 12 and Endpoint (Last Postbaseline Observation Up to Week 12)

  Weeks 4, 8, 12 and Endpoint (last postbaseline observation up to Week 12)

Study Arms (4)

1

EXPERIMENTAL

Armodafinil 50 mg/day

Drug: Armodafinil

2

EXPERIMENTAL

Armodafinil 150 mg/day

Drug: Armodafinil

3

EXPERIMENTAL

Armodafinil 250 mg/day

Drug: Armodafinil

4

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Armodafinil DRUG

Armodafinil 50 mg/day

1

Placebo OTHER

Placebo

4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient had a mild (Glasgow Coma Scale \[GCS\] score 13-15) or moderate (GCS score 9-12) closed TBI at the time of the injury, and the injury occurred 1 to 10 years prior to screening.
• The patient had a Glasgow Outcome Scale score of 5 at the screening visit.
• The patient had an Epworth Sleepiness Scale (ESS) score of at least 10 at screening.
• The patient had a mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of 4 naps) of less than 8 minutes at baseline.
• The patient had a Clinical Global Impression of Severity of Illness (CGI-S) rating relating to their excessive sleepiness of 4 or more at the screening and baseline visits.
• The patient had a complaint of excessive sleepiness (at least 5 days/week on average) for at least 3 months, and the excessive sleepiness began within 12 months of the TBI.
• Written informed consent was obtained.
• The patient was a man or woman of any ethnic origin 18 to 65 years of age.
• If admitted to an inpatient treatment facility, the patient was discharged at least 1 month prior to the screening visit.
• The patient did not have any medical or psychiatric disorders that could account for the excessive sleepiness.
• Women of childbearing potential (not surgically sterile or 2 years postmenopausal), used a medically accepted method of contraception, and continued use of one of these methods for the duration of the study (and for 30 days after participation in the study). Acceptable methods of contraception included: abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method, or intrauterine device (IUD).
• The patient was in otherwise good health, as judged by the investigator, on the basis of a medical and psychiatric history, physical examination, electrocardiogram (ECG), serum chemistry, hematology, and urinalysis.
• The patient was willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.
• The patient had a Mini Mental State Examination (MMSE) score of more than 26 at the screening visit.
• The patient was on stable dosages of medications (allowed by the protocol) for a minimum of 3 months (selective serotonin reuptake inhibitors \[SSRIs\] and serotonin-norepinephrine reuptake inhibitors \[SNRIs\]), 8 weeks (contraceptives), or 4 weeks (all other allowed medication) before the screening visit and was not likely to require a change in therapy for at least 12 weeks on the basis of the investigators' assessment.

You may not qualify if:

• The patient had a history of 2 or more episodes of transient loss of consciousness (LOC) without clear medical explanation, or had a history of known or suspected pseudo seizure (psychogenic seizure). Patients with a history of seizure or epilepsy may have been eligible following discussion with the medical monitor.
• The patient required, or was likely to require, treatment with anticonvulsant medication during the study, or had taken anticonvulsant medication within 6 months before the screening visit.
• The patient had an unstable or uncontrolled medical (including illnesses related to the cardiovascular \[including patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who had experienced the mitral valve prolapse syndrome\], renal, or hepatic systems or surgical) condition (treated or untreated) or was not a suitable candidate for treatment with armodafinil, as judged by the investigator.
• The patient had neurosurgery involving the brain or brainstem.
• The patient had a history of schizophrenia, bipolar disorder, psychotic depression, or other psychotic episode.
• The patient had any current Axis I disorder (including depression and posttraumatic stress disorder \[PTSD\]), as assessed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (SCID). The patient had any Axis II disorder (as assessed by SCID) that, in the opinion of the investigator, would affect patient participation in the study or full compliance with study procedures.
• The patient had a history of, or currently met The International Classification of Sleep Disorders, Edition 2 (ICSD 2) (American Academy of Sleep Medicine 2005) criteria for narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), shift work sleep disorder (SWSD), or any other sleep disorder associated with excessive daytime sleepiness; or the patient had a history of idiopathic hypersomnia, insomnia (requiring treatment), or sleep disorder before the development of the TBI.
• The patient had 85% or less sleep efficiency (sleep duration ÷ time in bed x 100%) as determined from nocturnal polysomnography (NPSG).
• The patient had any disorder that may interfere with drug absorption, distribution, metabolism, or excretion.
• The patient used any medications, including over-the-counter (OTC) medicines disallowed by the protocol, within 7 days or 5 half lives (medication or its active metabolites), whichever was longer, before the screening visit.
• The patient had a need for chronic pain medications.
• In the judgment of the investigator, the patient had a clinically significant deviation from normal in the physical examination.
• In the judgment of the investigator, the patient had any clinically significant ECG finding.
• The patient had a diagnosis of any type of dementia.
• The patient had a history of suicidal ideation (considered by the investigator to be of current clinical significance), or was currently suicidal.

Sponsors & Collaborators

• Cephalon, Inc.: lead

Study Sites (73)

Teva Investigational Site 58

Birmingham, Alabama, 35213, United States

Location

Teva Investigational Site 62

Tucson, Arizona, 85712, United States

Location

Teva Investigational Site 40

Tucson, Arizona, 85723, United States

Location

Teva Investigational Site 16

Hot Springs, Arkansas, 71913, United States

Location

Teva Investigational Site 5

Little Rock, Arkansas, 72205, United States

Location

Teva Investigational Site 44

Fountain Valley, California, 92708, United States

Location

Teva Investigational Site 49

La Palma, California, 90623, United States

Location

Teva Investigational Site 51

La Palma, California, 90623, United States

Location

Teva Investigational Site 71

Mather, California, 95655, United States

Location

Teva Investigational Site 55

San Diego, California, 92103, United States

Location

Teva Investigational Site 33

San Diego, California, 92161, United States

Location

Teva Investigational Site 53

Santa Monica, California, 90404, United States

Location

Teva Investigational Site 69

Wallingford, Connecticut, 06492, United States

Location

Teva Investigational Site 52

Hallandale, Florida, 33009, United States

Location

Teva Investigational Site 47

Miami, Florida, 33173, United States

Location

Teva Investigational Site 1

Orlando, Florida, 32806, United States

Location

Teva Investigational Site 18

Pembroke Pines, Florida, 33026, United States

Location

Teva Investigational Site 10

Spring Hill, Florida, 34609, United States

Location

Teva Investigational Site 38

St. Petersburg, Florida, 33707, United States

Location

Teva Investigational Site 17

Tampa, Florida, 33607, United States

Location

Teva Investigational Site 26

Atlanta, Georgia, 30321, United States

Location

Teva Investigational Site 12

Atlanta, Georgia, 30342, United States

Location

Teva Investigational Site 14

Atlanta, Georgia, 30342, United States

Location

Teva Investigational Site 68

Gainesville, Georgia, 30501, United States

Location

Teva Investigational Site 67

Macon, Georgia, 31201, United States

Location

Teva Investigational Site 29

Stockbridge, Georgia, 30281, United States

Location

Teva Investigational Site 15

Suwanee, Georgia, 30024, United States

Location

Teva Investigational Site 46

Chicago, Illinois, 60675-6714, United States

Location

Teva Investigational Site 54

Chicago, Illinois, 60675-6714, United States

Location

Teva Investigational Site 59

Chicago, Illinois, 60675-6714, United States

Location

Teva Investigational Site 28

Danville, Indiana, 46122, United States

Location

Teva Investigational Site 19

Fort Wayne, Indiana, 46805, United States

Location

Teva Investigational Site 2

Indianapolis, Indiana, 46250, United States

Location

Teva Investigational Site 39

Indianapolis, Indiana, 46260, United States

Location

Teva Investigational Site 41

Iowa City, Iowa, 52242, United States

Location

Teva Investigational Site 9

Shawnee Mission, Kansas, 66201, United States

Location

Teva Investigational Site 48

Louisville, Kentucky, 40217, United States

Location

Teva Investigational Site 32

Chevy Chase, Maryland, 20815-6901, United States

Location

Teva Investigational Site 37

Belmont, Massachusetts, 02478, United States

Location

Teva Investigational Site 70

Brighton, Massachusetts, 02135, United States

Location

Teva Investigational Site 22

Saginaw, Michigan, 48604, United States

Location

Teva Investigational Site 7

Hattiesburg, Mississippi, 39402, United States

Location

Teva Investigational Site 42

St Louis, Missouri, 63143, United States

Location

Teva Investigational Site 56

Lincoln, Nebraska, 68510, United States

Location

Teva Investigational Site 72

New York, New York, 10010, United States

Location

Teva Investigational Site 63

New York, New York, 10019, United States

Location

Teva Investigational Site 36

West Seneca, New York, 14224, United States

Location

Teva Investigational Site 11

Durham, North Carolina, 27710, United States

Location

Teva Investigational Site 45

Winston-Salem, North Carolina, 27157, United States

Location

Teva Investigational Site 31

Cincinnati, Ohio, 45227, United States

Location

Teva Investigational Site 34

Cincinnati, Ohio, 45246, United States

Location

Teva Investigational Site 57

Middleburg Heights, Ohio, 44130, United States

Location

Teva Investigational Site 30

Toledo, Ohio, 43623, United States

Location

Teva Investigational Site 3

Oklahoma City, Oklahoma, 73112, United States

Location

Teva Investigational Site 64

Clarks Summit, Pennsylvania, 18411, United States

Location

Teva Investigational Site 13

Jefferson Hills, Pennsylvania, 15025, United States

Location

Teva Investigational Site 65

Columbia, South Carolina, 29201, United States

Location

Teva Investigational Site 61

Germantown, Tennessee, 38139, United States

Location

Teva Investigational Site 60

Austin, Texas, 78756, United States

Location

Teva Investigational Site 25

Dallas, Texas, 75235, United States

Location

Teva Investigational Site 8

Houston, Texas, 77030, United States

Location

Teva Investigational Site 20

Houston, Texas, 77063, United States

Location

Teva Investigational Site 73

Kingwood, Texas, 77339, United States

Location

Teva Investigational Site 23

San Antonio, Texas, 78229, United States

Location

Teva Investigational Site 35

Midvale, Utah, 84047, United States

Location

Teva Investigational Site 66

Midvale, Utah, 84047, United States

Location

Teva Investigational Site 24

Richmond, Virginia, 23249, United States

Location

Teva Investigational Site 50

West Allis, Wisconsin, 53227, United States

Location

Teva Investigational Site 405

Berlin, 10117, Germany

Location

Teva Investigational Site 404

München, 80331, Germany

Location

Teva Investigational Site 501

Pisa, 56126, Italy

Location

Teva Investigational Site 704

Barcelona, 08003, Spain

Location

Teva Investigational Site 701

Madrid, 28036, Spain

Location

Related Publications (1)

• Menn SJ, Yang R, Lankford A. Armodafinil for the treatment of excessive sleepiness associated with mild or moderate closed traumatic brain injury: a 12-week, randomized, double-blind study followed by a 12-month open-label extension. J Clin Sleep Med. 2014 Nov 15;10(11):1181-91. doi: 10.5664/jcsm.4196.

  PMID: 25325609 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

The sponsor's decision to terminate the study early resulted in a small number of study participants and related limitations to the interpretation of the study results.

Results Point of Contact

• Title: Manager, Biopharmaceutics
• Organization: Teva Pharmaceuticals USA

clinicaltrialqueries@tevausa.com

1-866-384-5525

Study Officials

• Sponsor's Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2009
• First Posted: May 6, 2009
• Study Start: April 30, 2009
• Primary Completion: January 31, 2011
• Study Completion: January 31, 2011
• Last Updated: December 17, 2021
• Results First Posted: October 18, 2013

Record last verified: 2021-12

Locations

US (68); DE (2); ES (2); IT (1)