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

NCT01624480 | Completed Phase 1

• 2 other identifiers: C10953/11002012-005510-20
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 24

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.

Conditions

Narcolepsy

Keywords

Pediatric Narcolepsy

Outcome Measures

Primary Outcomes (15)

• 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 Outcomes (5)

• Mean sleep latency

  2 Days (Baseline + Day 1)

• Mean sleep latency

  Day 42

• Clinical Global Impression of Change (CGI-C)

  Day 1

• Clinical Global Impression of Change (CGI-C)

  Outpatient Visits Weeks 1 through 5, once per week

• Clinical Global Impression of Change (CGI-C)

  Day 42

Study Arms (3)

Armodafinil 50 mg

EXPERIMENTAL

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

Armodafinil 100 mg

EXPERIMENTAL

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

Armodafinil 150 mg

EXPERIMENTAL

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

Interventions

Armodafinil DRUG

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.

Also known as: R-modafinil, CEP-10953

Armodafinil 100 mg; Armodafinil 150 mg; Armodafinil 50 mg

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (24)

Teva Investigational Site 12

Birmingham, Alabama, United States

Location

Teva Investigational Site 17

Birmingham, Alabama, United States

Location

Teva Investigational Site 7

Little Rock, Arkansas, United States

Location

Teva Investigational Site 18

Orange, California, United States

Location

Teva Investigational Site 16

San Diego, California, United States

Location

Teva Investigational Site 4

Stanford, California, United States

Location

Teva Investigational Site 9

Clearwater, Florida, United States

Location

Teva Investigational Site 26

Miami Lakes, Florida, United States

Location

Teva Investigational Site 5

Spring Hill, Florida, United States

Location

Teva Investigational Site 25

Winter Park, Florida, United States

Location

Teva Investigational Site 1

Atlanta, Georgia, United States

Location

Teva Investigational Site 2

Atlanta, Georgia, United States

Location

Teva Investigational Site 20

Louisville, Kentucky, United States

Location

Teva Investigational Site 15

Grand Blanc, Michigan, United States

Location

Teva Investigational Site 3

West Seneca, New York, United States

Location

Teva Investigational Site 23

Raleigh, North Carolina, United States

Location

Teva Investigational Site 10

Toledo, Ohio, United States

Location

Teva Investigational Site 13

Oklahoma City, Oklahoma, United States

Location

Teva Investigational Site 19

West Chester, Pennsylvania, United States

Location

Teva Investigational Site 8

Houston, Texas, United States

Location

Teva Investigational Site 14

San Antonio, Texas, United States

Location

Teva Investigational Site 27

Everett, Washington, United States

Location

Teva Investigational Site 24

Seattle, Washington, United States

Location

Teva Investigational Site 200

Helsinki, Finland

Location

MeSH Terms

Conditions

Narcolepsy

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2012
• First Posted: June 20, 2012
• Study Start: July 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: December 1, 2015
• Last Updated: November 9, 2021

Record last verified: 2021-11

Locations

US (23); FI (1)