Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Armodafinil in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy

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

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.

Study Overview

• Status: Completed
• Conditions: Narcolepsy
• Intervention / Treatment: Drug: Armodafinil

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Teva Investigational Site 200
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Teva Investigational Site 12
    • Birmingham, Alabama, United States
      • Teva Investigational Site 17
  • Arkansas
    • Little Rock, Arkansas, United States
      • Teva Investigational Site 7
  • California
    • Orange, California, United States
      • Teva Investigational Site 18
    • San Diego, California, United States
      • Teva Investigational Site 16
    • Stanford, California, United States
      • Teva Investigational Site 4
  • Florida
    • Clearwater, Florida, United States
      • Teva Investigational Site 9
    • Miami Lakes, Florida, United States
      • Teva Investigational Site 26
    • Spring Hill, Florida, United States
      • Teva Investigational Site 5
    • Winter Park, Florida, United States
      • Teva Investigational Site 25
  • Georgia
    • Atlanta, Georgia, United States
      • Teva Investigational Site 1
    • Atlanta, Georgia, United States
      • Teva Investigational Site 2
  • Kentucky
    • Louisville, Kentucky, United States
      • Teva Investigational Site 20
  • Michigan
    • Grand Blanc, Michigan, United States
      • Teva Investigational Site 15
  • New York
    • West Seneca, New York, United States
      • Teva Investigational Site 3
  • North Carolina
    • Raleigh, North Carolina, United States
      • Teva Investigational Site 23
  • Ohio
    • Toledo, Ohio, United States
      • Teva Investigational Site 10
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Teva Investigational Site 13
  • Pennsylvania
    • West Chester, Pennsylvania, United States
      • Teva Investigational Site 19
  • Texas
    • Houston, Texas, United States
      • Teva Investigational Site 8
    • San Antonio, Texas, United States
      • Teva Investigational Site 14
  • Washington
    • Everett, Washington, United States
      • Teva Investigational Site 27
    • Seattle, Washington, United States
      • Teva Investigational Site 24

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Armodafinil 50 mg; In period 1, patients will receive a single 50-mg dose of armodafinil on day 1. In period 2, patients will receive a single 50-mg dose daily on days 1 through 42.	Drug: Armodafinil; The armodafinil tablets to be used in this study contain 50 mg of armodafinil and the following inactive ingredients: lactose monohydrate, starch, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and povidone.; Other Names: CEP-10953; R-modafinil
Experimental: Armodafinil 100 mg; In period 1, patients will receive a single 100 mg dose of armodafinil on day 1. In period 2, patients will receive a single 50-mg dose on day 1 then daily 100-mg doses on days 2 through 42.	Drug: Armodafinil; The armodafinil tablets to be used in this study contain 50 mg of armodafinil and the following inactive ingredients: lactose monohydrate, starch, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and povidone.; Other Names: CEP-10953; R-modafinil
Experimental: Armodafinil 150 mg; In period 1, patients will receive a single 150-mg dose of armodafinil on day 1. In period 2, patients will receive a single 50-mg dose on day 1, 100-mg doses on days 2 and 3, then daily 150-mg doses on days 4 through 42.	Drug: Armodafinil; The armodafinil tablets to be used in this study contain 50 mg of armodafinil and the following inactive ingredients: lactose monohydrate, starch, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and povidone.; Other Names: CEP-10953; R-modafinil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma drug concentration (Cmax) by inspection	Day 1 + up to 72 hours after administration
Time to maximum observed plasma drug concentration (tmax) by inspection	Day 1 + up to 72 hours after administration
Area under the plasma drug concentration by time curve from time 0 to infinity	Day 1 + up to 72 hours after administration
Area under the plasma drug concentration by time curve from time 0 to the time of the last measurable drug concentration	Day 1 + up to 72 hours after administration
Terminal half-life	Day 1 + up to 72 hours after administration
Terminal elimination rate constant	Day 1 + up to 72 hours after administration
Apparent total plasma clearance	Day 1 + up to 72 hours after administration
Apparent volume of distribution	Day 1 + up to 72 hours after administration
Predicted accumulation ratio	Day 1 + up to 72 hours after administration
Maximum observed plasma drug concentration (Cmax)	Day 42 + up to 72 hours after administration
Time to maximum observed plasma drug concentration	Day 42 + up to 72 hours after administration
AUC over 1 dosing interval	Day 42 + up to 72 hours after administration
AUC 0-t	Day 42 + up to 72 hours after administration
Observed accumulation ratio	Day 42 + up to 72 hours after administration
Steady-state accumulation ratio	Day 42 + up to 72 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean sleep latency	An objective assessment of sleepiness that measures the likelihood of falling asleep. The test consists of multiple naps performed on the day before study drug administration in period 1 and on the day of study drug administration in period 1. For each nap, sleep latency will be measured as the elapsed time from lights-out to the first epoch scored as sleep. Mean sleep latency is calculated for each day as the average of the sleep latencies from each nap on that day.	2 Days (Baseline + Day 1)
Mean sleep latency	An assessment by the investigator of change in the patient's severity of excessive sleepiness during the course of the study. The clinician will ask the guardian to assess the child's home behavior over the past week.	Day 42
Clinical Global Impression of Change (CGI-C)	An assessment by the investigator of change in the patient's severity of excessive sleepiness during the course of the study. The clinician will ask the guardian to assess the child's home behavior over the past week.	Day 1
Clinical Global Impression of Change (CGI-C)	The Clinical Global Impression of Change (CGI-C) is an assessment by the investigator of change in the patient's severity of excessive sleepiness during the course of the study. The clinician will ask the guardian to assess the child's home behavior over the past week. The CGI-C ratings will be assessed using the following 7 categories and scoring assignments: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse	Outpatient Visits Weeks 1 through 5, once per week
Clinical Global Impression of Change (CGI-C)	The Clinical Global Impression of Change (CGI-C) is an assessment by the investigator of change in the patient's severity of excessive sleepiness during the course of the study. The clinician will ask the guardian to assess the child's home behavior over the past week. The CGI-C ratings will be assessed using the following 7 categories and scoring assignments: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse	Day 42

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 18, 2012
• First Submitted That Met QC Criteria: June 18, 2012
• First Posted (Estimate): June 20, 2012

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Pediatric Narcolepsy
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Sleepiness; Narcolepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: C10953/1100; 2012-005510-20 (EudraCT Number)