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

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01624480
• Collaborator: (none)
• Enrollment: 40
• Locations: 24
• Arms: 3
• Duration (Months): 41
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Narcolepsy	Drug: Armodafinil	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jul 1, 2012
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

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: R-modafinil CEP-10953
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: R-modafinil CEP-10953
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: R-modafinil CEP-10953

Outcome Measures

Primary Outcome Measures

1. Maximum observed plasma drug concentration (Cmax) by inspection [Day 1 + up to 72 hours after administration]

2. Time to maximum observed plasma drug concentration (tmax) by inspection [Day 1 + up to 72 hours after administration]

3. Area under the plasma drug concentration by time curve from time 0 to infinity [Day 1 + up to 72 hours after administration]

4. 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]

5. Terminal half-life [Day 1 + up to 72 hours after administration]

6. Terminal elimination rate constant [Day 1 + up to 72 hours after administration]

7. Apparent total plasma clearance [Day 1 + up to 72 hours after administration]

8. Apparent volume of distribution [Day 1 + up to 72 hours after administration]

9. Predicted accumulation ratio [Day 1 + up to 72 hours after administration]

10. Maximum observed plasma drug concentration (Cmax) [Day 42 + up to 72 hours after administration]

11. Time to maximum observed plasma drug concentration [Day 42 + up to 72 hours after administration]

12. AUC over 1 dosing interval [Day 42 + up to 72 hours after administration]

13. AUC 0-t [Day 42 + up to 72 hours after administration]

14. Observed accumulation ratio [Day 42 + up to 72 hours after administration]

15. Steady-state accumulation ratio [Day 42 + up to 72 hours after administration]

Secondary Outcome Measures

1. Mean sleep latency [2 Days (Baseline + Day 1)]

   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. Mean sleep latency [Day 42]

   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.

3. Clinical Global Impression of Change (CGI-C) [Day 1]

   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.

4. Clinical Global Impression of Change (CGI-C) [Outpatient Visits Weeks 1 through 5, once per week]

   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

5. Clinical Global Impression of Change (CGI-C) [Day 42]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT01624480
• Other Study ID Numbers: C10953/1100; 2012-005510-20
• First Posted: Jun 20, 2012
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.: Pediatric Narcolepsy
• Additional relevant MeSH terms: Narcolepsy; Sleepiness; Modafinil

Study Results

No Results Posted as of Nov 9, 2021