A 12-week, randomized, double-blind, placebo-controlled, parallel-group. fixed-dosage study to evaluate the efficacy and safety of armodafinil (50, 150, and 250 mg/day) as treatment for patients with excessive sleepiness associated with mild or moderate closed traumatic brain injury - ?Estudio de 12 semanas, aleatorizado, doble-ciego controlado con placebo, de grupos paralelos con dosis fijas para evaluar la eficacia y la seguridad de Armodafinil (50, 150 y 250 mg/día) en el tratamiento de pacientes con somnolencia excesiva asociada a un trauma cráneo-cerebral no penetrante leve o moderado - C10953/3067/ES/MN

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-014545-83-ES
• Date of registration: 05/01/2010
• Prospective Registration: Yes
• Primary sponsor: Cephalon Inc.
• Public title: A 12-week, randomized, double-blind, placebo-controlled, parallel-group. fixed-dosage study to evaluate the efficacy and safety of armodafinil (50, 150, and 250 mg/day) as treatment for patients with excessive sleepiness associated with mild or moderate closed traumatic brain injury - ?Estudio de 12 semanas, aleatorizado, doble-ciego controlado con placebo, de grupos paralelos con dosis fijas para evaluar la eficacia y la seguridad de Armodafinil (50, 150 y 250 mg/día) en el tratamiento de pacientes con somnolencia excesiva asociada a un trauma cráneo-cerebral no penetrante leve o moderado - C10953/3067/ES/MN
• Scientific title: A 12-week, randomized, double-blind, placebo-controlled, parallel-group. fixed-dosage study to evaluate the efficacy and safety of armodafinil (50, 150, and 250 mg/day) as treatment for patients with excessive sleepiness associated with mild or moderate closed traumatic brain injury - ?Estudio de 12 semanas, aleatorizado, doble-ciego controlado con placebo, de grupos paralelos con dosis fijas para evaluar la eficacia y la seguridad de Armodafinil (50, 150 y 250 mg/día) en el tratamiento de pacientes con somnolencia excesiva asociada a un trauma cráneo-cerebral no penetrante leve o moderado - C10953/3067/ES/MN
• Date of first enrolment: 24/02/2010
• Target sample size: 620
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-014545-83
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic, France, Germany, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
- mild (Glasgow Coma Scale [GCS] score 13-15) or moderate (GCS 9-12) closed TBI at the time of injury, and injury occurred 1 to 10 years prior to screening. TBI is defined as traumatically induced physiologic disruption of brain function as manifested by 1 of the following:
any period of LOC, any loss of memory for events immediately before or after the accident, any alteration of mental state, focal neurological deficits (may or may not be transient)
- the patient has a Glasgow Outcome Scale score of 5 at the screening visit
- the patient has an ESS score of at least 10 at screening
- the patient has a mean sleep latency on the MSLT (average of 4 naps) of less than 8 minutes at baseline
- the patient has 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 has 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 is obtained
- the patient is a man or woman of any ethnic origin 18 to 65 years of age
- if admitted to an in-patient treatment facility, the patient was discharged at least 1 month prior to the screening visit
- the patient does 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), must use a medically accepted method of contraception, and must continue 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 include: abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, mplanted, and injected) in conjunction with a barrier method, or intrauterine device (IUD).
- the patient is in otherwise good health, as judged by the investigator, on the basis of a medical and psychiatric history, physical examination, ECG, serum chemistry, hematology, and urinalysis
- the patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol
- the patient has Mini-Mental State Exam (MMSE) score of more than 26 at the screening visit
- the patient is on stable dosages of medications (allowed by the protocol) for a minimum of 8 weeks before the screening visit and is not likely to require a change in therapy for at least 12 weeks on the basis of the investigators? assessment.
- the patient has had no more than 1 head injury fulfilling the criteria for TBI
- the patient has a habitual bedtime between 21:00 and 23:00
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- the patient has a history of 2 or more episodes of transient loss of consciousness without clear medical explanation, or has a history of known or suspected pseudoseizure (psychogenic seizure). Patients with a history of seizure or epilepsy may be eligible following discussion with the medical monitor
- the patient requires, or is likely to require, treatment with anticonvulsant medication during the study; or has taken anticonvulsant medication within 6 months before the screening visit
- the patient has 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 have experienced the mitral valve prolapse syndrome]), renal, or hepatic systems or surgical condition (treated or untreated) or is not a suitable candidate for treatment with armodafinil, as judged by the investigator
- the patient has had neurosurgery involving the brain or brainstem
- the patient has a history of schizophrenia, bipolar disorder, psychotic depression, or other psychotic episode
- the patient has any current Axis I disorder (including depression and posttraumatic stress disorder [PTSD]) or any Axis II disorder, that in the opinion of the investigator would affect patient participation in the study or full compliance with study procedures
- the patient has a history of, or currently meets ICSD-2 criteria for narcolepsy, OSAHS, SWSD, or any other sleep disorder associated with excessive daytime sleepiness; or the patient has a history of idiopathic hypersomnia, insomnia (requiring treatment), or sleep disorder before the development of the TBI
- the patient has 85% or less sleep efficiency as determined from NPSG
- the patient has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion
- the patient has used any medications including OTC medicines disallowed by the protocol within 7 days or 5 half-lives (medication or its active metabolites), whichever is longer, before the baseline visit
- the patient has a need for chronic pain medications
- in the judgment of the investigator, the patient has a clinically significant deviation from normal in the physical examination
- in the judgment of the investigator, the patient has any clinically significant ECG
- the patient has a diagnosis of any type of dementia
- the patient has a history of suicidal ideation (considered to be currently clinical significant), or is currently suicidal
- the patient has a known hypersensitivity to Armodafinil, racemic modafinil, or any component of the study drug tablets
- the patient has a history of any clinically significant cutaneous drug reaction, or a history of clinically significant hypersensitivity reaction, including multiple allergies or drug reactions
- the patient has a clinical laboratory test value(s) outside the range(s) specified below, and medical monitor has not provided written approval for study participation:
? hemoglobin <110 g/L (11.0 g/dL) (men) or <100 g/L (10.0 g/dL) (women)
? absolute neutrophil count (ANC) <1.5 x 109/L (<1500/mm3)
? platelet count <100 x 109/L (<100000/mm3)
? sodium <130 mEq/L
? potassium >5.5 mEq/L
? glucose >200 mg/dL (unless a repeat measurement of glucose in the fasting state is <140 mg/dL)
? creatinine clearance <60 mL/min (calculated by the Cockcroft-Gault formula)
? aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpe

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with excessive Sleepiness associated with mild or moderate closed Traumatic Brain Injury (TBI)
MedDRA version: 12.0 Level: LLT Classification code 10060690 Term: Traumatic brain injury
MedDRA version: 12.0 Level: LLT Classification code 10015595 Term: Excessive daytime sleepiness

Intervention(s)

Product Name: Armodafinil
Product Code: CEP-10953
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Armodafinil
CAS Number: 112111-43-0
Current Sponsor code: CEP-10953
Other descriptive name: R-modafinil
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of the sudy 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) by measuring mean sleep latency from the Multiple Sleep Latency Test (MSLT) (20-minute version; average of 4 naps at 0900, 1100, 1300, abd 1500) and proportion of responders (patients who are much or very much improved) according to the Clinical Global Impression of Change (CGI-C) ratings relating to excessive sleepiness at week 12 (or last postbaseline observation).

Secondary Objective: ? to evaluate health-related quality of life in patients assessed by the TBI-WIS at w 4, 8, 12 (or last postbaseline observation)
? to evaluate the effect of armodafinil treatment on excessive sleepiness:
mean sleep latency from the MSLT assessed at w 4, 8, 12 (average of 4 naps at 0900, 1100, 1300, and 1500), CGI-C at w 2, 4, 8, 12, ESS scores at w 12 (or last postbaseline observation)
? to evaluate the overall safety and tolerability of armodafinil during 12 weeks of double-blind treatment:
AEs, clinical laboratory tests at w 4, 8, 12 (or last postbaseline observation), vital signs at w 2, 4, 8, 12 (or last postbaseline observation), physical examinations, incll skin examinations and body weight, at w 12 (or last postbaseline observation), ECG at w 12 (or last postbaseline observation), concomitant medication
? to evaluate the effect of armodafinil treatment on nighttime sleep as assessed by NPSG at w 2, 4, 12 (or last postbaseline observation)

Primary end point(s): The primary efficacy measures and endpoints for this study are the MSLT and CGI-C assessed at week 12 (or last postbaseline observation).

Secondary ID(s)

C10953/3067/ES/MN