Clinical trial NCT01624480: Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Armodafinil in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy
Official title: A Randomized, Open-Label Study to Characterize the Pharmacokinetics, Pharmacodynamics, and Safety of Single and Multiple Doses of Armodafinil (50, 100, and 150 mg/Day) in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Narcolepsy
Keywords: Pediatric Narcolepsy
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2012-06-20
Enrollment: 40
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the pharmacokinetics, pharmacodynamics, and safety of single and multiple doses of armodafinil (50, 100, and 150 mg/day) in children and adolescents with excessive sleepiness associated with narcolepsy.


Eligibility criteria: Inclusion Criteria:

* Written informed consent is obtained from each patient's parent or legal guardian and written assent is obtained from each patient.
* The patient is a male or female 6 through 17 years of age with a body mass index (BMI) equal to or greater than 10th percentile for age and gender, inclusive.
* The patient has a diagnosis of narcolepsy with cataplexy or narcolepsy without cataplexy according to the criteria established by the International Classification of Sleep Disorders (ICSD)-2 for narcolepsy.

Exclusion Criteria:

* The patient has any clinically significant uncontrolled medical condition (treated or untreated) other than narcolepsy.
* The patient has a clinically significant deviation from normal in ECG, physical examination or vital sign findings, as determined by the investigator or medical monitor.
* The patient is pregnant or lactating. (Any patient becoming pregnant during the study will be withdrawn from the study)
* The patient has any history of seizures, including febrile seizures, or a family history of seizures (in parents or siblings) which is not a consequence of trauma, stroke, or metabolic disturbance.
* The patient has a history of head trauma associated with loss of consciousness.
* The patient has current suicidal ideation, a history of a suicidal ideation, or a history of a suicide attempt.
* The patient has a history of major depressive disorder, bipolar disorder, other significant mood disorders, schizophrenia and other psychotic disorders, eating disorders, or has a family history of suicide.
* The patient has left ventricular hypertrophy or the patient has mitral valve prolapse and has experienced mitral valve prolapse syndrome.
* The patient has received any investigational drug within 30 days or 5 half-lives (whichever is longer) before the 1st dose of study drug, or in the case of a new chemical entity, 3 months or 5 half-lives (whichever is longer) before the 1st dose of study drug.

  * The patient has used any monoamine oxidase inhibitors (MAOIs) or stimulants within 14 days or 5 half-lives (whichever is longer) of the baseline visit.
  * The patient has used modafinil or armodafinil within 4 weeks of the baseline visit.
  * The patient has used an inducer of CYP3A4/5 within 28 days prior to study drug administration.
  * The patient has used an inhibitor of CYP3A4/5 within 14 days or 5 half lives (whichever is longer) prior to study drug administration.
  * The patient has a known sensitivity or idiosyncratic reaction to any compound present in modafinil or armodafinil, their related compounds, or to any metabolites or compound listed as being present in these medications.
  * 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
  * Other criteria apply, please contact the investigator for additional information

Primary outcomes:
measure: Maximum observed plasma drug concentration (Cmax) by inspection
timeFrame: Day 1 + up to 72 hours after administration
measure: Time to maximum observed plasma drug concentration (tmax) by inspection
timeFrame: Day 1 + up to 72 hours after administration
measure: Area under the plasma drug concentration by time curve from time 0 to infinity
timeFrame: Day 1 + up to 72 hours after administration
measure: Area under the plasma drug concentration by time curve from time 0 to the time of the last measurable drug concentration
timeFrame: Day 1 + up to 72 hours after administration
measure: Terminal half-life
timeFrame: Day 1 + up to 72 hours after administration
measure: Terminal elimination rate constant
timeFrame: Day 1 + up to 72 hours after administration
measure: Apparent total plasma clearance
timeFrame: Day 1 + up to 72 hours after administration
measure: Apparent volume of distribution
timeFrame: Day 1 + up to 72 hours after administration
measure: Predicted accumulation ratio
timeFrame: Day 1 + up to 72 hours after administration
measure: Maximum observed plasma drug concentration (Cmax)
timeFrame: Day 42 + up to 72 hours after administration
measure: Time to maximum observed plasma drug concentration
timeFrame: Day 42 + up to 72 hours after administration
measure: AUC over 1 dosing interval
timeFrame: Day 42 + up to 72 hours after administration
measure: AUC 0-t
timeFrame: Day 42 + up to 72 hours after administration
measure: Observed accumulation ratio
timeFrame: Day 42 + up to 72 hours after administration
measure: Steady-state accumulation ratio
timeFrame: Day 42 + up to 72 hours after administration
Secondary outcomes:
measure: Mean sleep latency
timeFrame: 2 Days (Baseline + Day 1)
measure: Mean sleep latency
timeFrame: Day 42
measure: Clinical Global Impression of Change (CGI-C)
timeFrame: Day 1
measure: Clinical Global Impression of Change (CGI-C)
timeFrame: Outpatient Visits Weeks 1 through 5, once per week
measure: Clinical Global Impression of Change (CGI-C)
timeFrame: Day 42
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Teva Investigational Site 12
state: Alabama
city: Birmingham
country: United States
facility: Teva Investigational Site 17
state: Alabama
city: Little Rock
country: United States
facility: Teva Investigational Site 7
state: Arkansas
city: Orange
country: United States
facility: Teva Investigational Site 18
state: California
city: San Diego
country: United States
facility: Teva Investigational Site 16
state: California
city: Stanford
country: United States
facility: Teva Investigational Site 4
state: California
city: Clearwater
country: United States
facility: Teva Investigational Site 9
state: Florida
city: Miami Lakes
country: United States
facility: Teva Investigational Site 26
state: Florida
city: Spring Hill
country: United States
facility: Teva Investigational Site 5
state: Florida
city: Winter Park
country: United States
facility: Teva Investigational Site 25
state: Florida
city: Atlanta
country: United States
facility: Teva Investigational Site 1
state: Georgia
city: Atlanta
country: United States
facility: Teva Investigational Site 2
state: Georgia
city: Louisville
country: United States
facility: Teva Investigational Site 20
state: Kentucky
city: Grand Blanc
country: United States
facility: Teva Investigational Site 15
state: Michigan
city: West Seneca
country: United States
facility: Teva Investigational Site 3
state: New York
city: Raleigh
country: United States
facility: Teva Investigational Site 23
state: North Carolina
city: Toledo
country: United States
facility: Teva Investigational Site 10
state: Ohio
city: Oklahoma City
country: United States
facility: Teva Investigational Site 13
state: Oklahoma
city: West Chester
country: United States
facility: Teva Investigational Site 19
state: Pennsylvania
city: Houston
country: United States
facility: Teva Investigational Site 8
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 14
state: Texas
city: Everett
country: United States
facility: Teva Investigational Site 27
state: Washington
city: Seattle
country: United States
facility: Teva Investigational Site 24
state: Washington
city: Helsinki
country: Finland
facility: Teva Investigational Site 200
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: