Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Doses of Zolpidem in Children

NCT00494468 | Completed Phase 1

• 1 other identifier: PPRU-10590
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 11

Brief Summary

This is a multicenter trial to evaluate the single-dose safety, tolerability and pharmacokinetics-pharmacodynamics of Zolpidem in a group of children with sleep disturbances stratified by age and dose.

Conditions

Insomnia; Sleep Disorder

Keywords

Insomnia; Sleep Disorder; Sleep Deprivation

Outcome Measures

Primary Outcomes (9)

• Safety will be assessed by collection of reported adverse events or findings on physical examination or laboratory assessments.

• The primary pharmacokinetic outcome measures for this study will include the Zolpidem Cmax, Tmax, t1/2, AUC (zero to 12 hours and zero to infinity).

• Polysomnography, including an electroencephalogram, electrooculogram and electromyogram will be performed on two occasions and represents the primary pharmacodynamic outcome assessment for this study.

• Measures will include:

• Global sleep parameters: time to sleep, total sleep time, duration of sleep period, sleep efficiency, frequency of shifts between sleep stages and number and duration of awakenings

• Sleep Latencies; sleep onset latency, Rapid Eye Movement, (REM) latency, slow-wave sleep,(SWS) latency

• Sleep Stages (as absolute and relative proportions thereof: sleep stages I, II, III and IV; sleep stage REM; stage awake

• Non-Rem/REM Cycle Parameters: duration of the cycles, REM sleep per cycle, SWS sleep per cycle, number of cycles;

• Pharmacodynamic outcomes also will be assessed using activity-based monitoring or actigraphy. This technique has demonstrated ability to measure dose-related effects of hypnotics.

Secondary Outcomes (1)

• Secondary outcome pharmacokinetic outcome measures will include estimation of the apparent Zolpidem Vd/F and CI/F.

Interventions

Zolpidem DRUG

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female between the ages of 2 years and 18 years.
• Written consent must be obtained form the parent/legal guardian for all minors. Written assent must be obtained from all minors \> 6 years of age.
• Female subjects of child-bearing potential must not be pregnant and if females are fertile and sexually active, must have documented a negative urine HCG and assure use of effective contraception acceptable to the investigator (abstinence accepted) during the study period.
• Subjects must meet the following criteria for a diagnosis of insomnia as determined by the subject's private physician or study investigator and subject's history:
• the complaint is significant difficulty (defined by frequency, severity, and/or chronicity) initiating or maintaining sleep;. The problem is viewed problematic by the child and/or caregiver;
• the sleep disturbance causes clinically significant impairment in school performance, behavior, learning, or development for the child as reported by the child and/or caregiver;
• the sleep disturbance does not occur exclusively in the context of an intrinsic dyssomnia such as narcolepsy, restless legs syndrome, or sleep-related breathing disorders; a circadian rhythm disorder; or a parasomnia;
• the sleep disturbance is not attributable to either the direct physiologic effect of a drug of abuse or misuse of a prescribed medication.

You may not qualify if:

• Pregnancy and/or breastfeeding;
• The presence of any untreated (where treatment is available), or unstable, progressive, or evolving clinically significant renal, endocrine, hepatic, respiratory, cardiovascular, neurologic, hematologic, immunologic, cerebrovascular disease or malignancy;
• Elevations in screening blood tests of renal (SCr) and liver (ALT, AST and/or bilirubin) \> 2 times the upper limit of normal for age.
• Receiving any medications that may modulate Zolpidem metabolism, primarily drugs that will enhance or reduce the activity of CYP450 3A, 2C9, or 2D6 activity. Note: If patient is receiving a medication that might be considered an inducer or an inhibitor, please discuss with the PI prior to excluding them.
• Receiving any medications with sleep-impairing properties at a dose/dose interval that would be judged by the study investigator as to interfere with the assessment of Zolpidem sleep response.
• Currently using any systemic contraceptive steroids including: oral contraceptives, transdermal patch, vaginal insert, levonorgestrel implant and medroxyprogesterone acetate contraceptive injection.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead
• Sanofi-Synthelabo: collaborator

Study Sites (11)

Arkansas Children's Hospital Research Center Inc.

Little Rock, Arkansas, 72202, United States

Location

University of California at San Diego

La Jolla, California, 92093, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Louisiana State University Health Sciences Center

Shreveport, Louisiana, 71103, United States

Location

Children's Mercy Hospital & Clinics

Kansas City, Missouri, 64108, United States

Location

Children's Hospital Research Foundation

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Tennessee College of Medicine

Memphis, Tennessee, 38103, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Sleep Deprivation

Interventions

Zolpidem

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Nervous System Diseases; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey L. Blumer, Ph.D., M. D.

  Rainbow Babies and Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 28, 2007
• First Posted: June 29, 2007
• Study Start: October 1, 2002
• Study Completion: March 1, 2004
• Last Updated: June 29, 2007

Record last verified: 2005-11

Locations

US (11)