A 12-Month, open-label Study to evaluate the Safety, Tolerability, and Efficacy of Armodafinil (150 and 250 mg/day) as Treatment for Patients with excessive Sleepiness associated with mild or moderte closed Traumatic Brain Injury

• Register: EUCTR
• Last refreshed on: 30 March 2020
• Main ID: EUCTR2009-014544-11-DE
• Date of registration: 18/05/2010
• Prospective Registration: Yes
• Primary sponsor: Cephalon Inc
• Public title: A 12-Month, open-label Study to evaluate the Safety, Tolerability, and Efficacy of Armodafinil (150 and 250 mg/day) as Treatment for Patients with excessive Sleepiness associated with mild or moderte closed Traumatic Brain Injury
• Scientific title: A 12-Month, open-label Study to evaluate the Safety, Tolerability, and Efficacy of Armodafinil (150 and 250 mg/day) as Treatment for Patients with excessive Sleepiness associated with mild or moderte closed Traumatic Brain Injury
• Date of first enrolment: 28/07/2010
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-014544-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
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. 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)
Note: In the absence of GCS data, medical records or history from the patient and reliable informant indicating that, at the time of the injury, the patient fulfilled the criteria for TBI as noted above are acceptable. In addition, in the absence of GCS data, any period of LOC must have lasted no more than 30 minutes and any posttraumatic amnesia must have lasted no more than 24 hours.
(b) The patient has a Glasgow Outcome Scale score of 5 at the screening visit.
(c) The patient has an ESS score of at least 10 at screening.
(d) The patient has a mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of 4 naps) of less than 8 minutes.
(e) The patient has a CGI-S rating relating to their excessive sleepiness of 4 or more at the screening and baseline visits.
(f) 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.
(g) Written informed consent is obtained.
(h) The patient is a man or woman of any ethnic origin 18 to 65 years of age.
(i) If admitted to an in-patient treatment facility, the patient was discharged at least 1 month prior to the screening visit.
(j) The patient does not have any medical or psychiatric disorders that could account for the excessive sleepiness.
(k) 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, implanted, and injected) in conjunction with a barrier method, or intrauterine device (IUD).
(l) 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.
(m) The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.
(n) The patient has Mini-Mental State Exam (MMSE) score of more than 26 at the screening visit.
(o) The patient is on stable dosages of medications (allowed by the protocol) for a minimum of 3 months (SSRIs and SNRIs), 8 weeks (contraceptives), or 4 weeks (all other allowed medication) 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.
(q) The patient has a habitual bedtime between 2100 and 2400.
(r) The patient had no other head injuries that, based on medical records or history, were temporally related to the onset or to any worsening of excessive sleepiness.
(s) The patient had no other head injury fulfilling the criteria for TBI within +/- one year of the TBI identified.
Rollover Patients From Study 3067:
(r) The patient has complete
Exclusion criteria:
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.
Patient requires treatment with anticonvulsant medication during the study,
or has taken anticonvulsant medication within 6 months before the screening visit.
Patient has an unstable or uncontrolled medical (including illnesses related to the cardiovascular, 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.
Patient has had neurosurgery involving the brain or brainstem.
Patient has a history of schizophrenia, bipolar disorder, psychotic depression, or other psychotic episode.
Patient has any current Axis I disorder, assessed by SCID or with any Axis II disorder, as assessed by SCID, that would affect patient participation in the study or full compliance with study procedures.
Patient has a history of, or currently meets the 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, or sleep disorder before the development of the TBI.
Patient has 85% or less sleep efficiency as determined from nocturnal polysomnography.
Patient has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion.
Patient has used any medications including OTC medicines disallowed by
the protocol within 7 days or 5 half-lives, whichever is longer, before the screening visit.
Patient has a need for chronic pain medications.
Patient has a clinically significant deviation from normal in the physical examination.
Patient has any clinically significant ECG.
Patient has a diagnosis of dementia.
Patient has a history of suicidal ideation, or is currently suicidal.
Patient has a known hypersensitivity to armodafinil, racemic modafinil, or any component of the study drug tablets.
Patient has a history of any clinically significant cutaneous drug reaction, or a history of clinically significant hypersensitivity reaction, or drug reaction.
Patient has a clinical laboratory test value(s) outside the range(s) specified below:
? hemoglobin <110 g/L (11.0 g/dL) (men) or <100 g/L (10.0 g/dL) (women)
? 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
? creatinine clearance <60 mL/min
? AST, ALT, GGT, or AP =2 times the upper limit of normal
? total bilirubin >25.7 µmol/L (1.5 mg/dL)
Subject has a history (within the past 5 years) of alcohol, narcotic, or any other drug abuse (with the exception of nicotine) as defined by the DSM-IV-TR, or the subject has current evidence of substance use, without medical explanation.
Patient has taken armodafinil, modafinil, or other stimulant medication for excessive
sleepiness within 1 month of the screening visit.
Patient is a pregnant or lactating woman.
Patient is known to have tested positive for HIV.
Patient consumes an average of more than 600 mg of caffeine per day, including coffee, tea and/or other caffeine-containing beverages or food.
Patient has used any investigational drug within 1 month before the screening visit.
Patient is receiving workmen’s compensation or is in active l

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

Health Condition(s) or Problem(s) studied

Excessive sleepiness accociated with mild or moderate closed traumatic brain injury
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: Tablet
INN or Proposed INN: 2-[(R)-(diphenymethyl)sulfinyl]acetamide
CAS Number: 112111-43-0
Current Sponsor code: CEP-10953
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Armodafinil
Product Code: CEP-10953
Pharmaceutical Form: Tablet
INN or Proposed INN: 2-[(R)-(diphenymethyl)sulfinyl]acetamide
CAS Number: 112111-43-0
Current Sponsor code: CEP-10953
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Name: Armodafinil
Product Code: CEP-10953
Pharmaceutical Form: Tablet
INN or Proposed INN: 2-[(R)-(diphenymethyl)sulfinyl]acetamide
CAS Number: 112111-43-0
Current Sponsor code: CEP-10953
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Secondary Objective: The secondary objectives are:
- to evaluate the long-term efficacy of armodafinil treatment for excessive sleepiness as assessed by the change from baseline in ESS scores, CGI-S ratings for excessive sleepiness, proportion of patients with improvement based on CGI-S ratings; all on diverse time points.
- to evaluate the effect of armodafinil teatment on health-related quality-of-life in patients woh are currently employed as assessed by the change form baseline in TBI-WIS scores at different time points
- to evaluate the effects of armodafinil treatment on subjective cognitive functioning as assessed by the change from baseline in the MOS-CF6 scores at different time points

Main Objective: The primary objective is to evaluate the safety and tolerability of long-term (12 months) armodafinil treatment in patients with excessive sleepiness associated with mild or moderate closed TBI (traumatic brain injury). Safety and tolerability will be assessed by monitoring adverse events and concomitant medication usage throughout the study, and clinical laboratory test results (serum chemistry, hematology, and urinalysis), vital signs measurements, and ECG and phsical examination findings (incl. skin examinations and body weight measurements), suicidal ideation and suicidal behavior using the Coumbia Suicide Severity Rating Scale Since Last Visit version (C-SSRS-SLV), and symptoms of depression usting the self-reported Hamilton Depression Rating Scale, 6-item (S-HAM-D6) at specified time points during the study.

Primary end point(s): To evaluate the safety and tolerability of long-term (12 months) Armodafinil treatment in patients with excessive sleepiness associated with mild or moderate closed traumatic brain injury (TBI). Safety and tolerability will be assessed by monitoring adverse events and concomitant medicaiton usage throughout the study, and clinical laboratory test results (serum chemistry, hematology, and urinalysis), vital signs measurements, and electrocardiogram (ECG) and physical examination findings (including skin examinations and body weight measurements) at specified time pints during the study.

Secondary ID(s)

C10953/3069/ES/MN

2009-014544-11-ES

Ethics review

Status: Approved
Approval date: 28/07/2010
Contact:

Results

• Results available: Yes
• Date Posted: 16/11/2016
• Date Completed: 31/01/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-014544-11/results