Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Doses of Zolpidem in Children
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Zolpidem Doses in Children Ages 2 to 18 Years of Age|
- 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 outcome pharmacokinetic outcome measures will include estimation of the apparent Zolpidem Vd/F and CI/F.
|Study Start Date:||October 2002|
|Estimated Study Completion Date:||March 2004|
The consequences of sleep deprivation to the productivity of the individual and society are extensive. (Most clinicians and patients believe that insomnia becomes a clinical problem requiring therapy when excessive daytime sleepiness impairs cognition and mood, interfering with a patient's performance of functions that require alertness. Chronic sleep deprivation often leads to adverse personal, medical and psychiatric complications, underscoring the common request of patients for treatment by their physician.
With an increasing focus on the problem of sleep deprivation in children of all ages, our appreciation of the scope of the problem is expanding. It is estimated that up to 40 % of infants experience difficulty in settling and frequent nighttime wakings with sleep disturbances including bedtime resistance, delayed onset of sleep, and disruptive night wakings occurring in 25 to 50 % of preschoolers. In school-aged children, parents reported an incidence of bedtime resistance in 15 % of their children.
Very limited data exist describing the pharmacokinetics of zolpidem in pediatrics. Colle and colleagues reported the zolpidem clearance to be 3 times greater in children (n=6) compared to young adults (n=104) though Cmax and AUC values were similar despite a higher zolpidem dose (mg/Kg) in the children. Unfortunately these data raise more questions than they answer regarding zolpidem disposition relative to age and highlight the need to comprehensively determine zolpidem disposition characteristics across a broad age range of pediatric subjects.
In summary, although researchers have been hesitant to include children in drug studies, the data indicate that pediatric sleep disturbance have a negative health impact on children and warrant pharmacologic intervention. Studies to identify the appropriate drug and dosage for children of all ages are essential in addressing this health problem that impacts the child and his/her family.
|United States, Arkansas|
|Arkansas Children's Hospital Research Center Inc.|
|Little Rock, Arkansas, United States, 72202|
|United States, California|
|University of California at San Diego|
|La Jolla, California, United States, 92093|
|United States, Colorado|
|National Jewish Medical and Research Center|
|Denver, Colorado, United States, 80206|
|United States, Louisiana|
|Louisiana State University Health Sciences Center|
|Shreveport, Louisiana, United States, 71103|
|United States, Missouri|
|Children's Mercy Hospital & Clinics|
|Kansas City, Missouri, United States, 64108|
|United States, Ohio|
|Children's Hospital Research Foundation|
|Cincinnati, Ohio, United States, 45229|
|Rainbow Babies and Children's Hospital|
|Cleveland, Ohio, United States, 44106|
|Columbus, Ohio, United States, 43205|
|United States, Pennsylvania|
|The Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Tennessee|
|University of Tennessee College of Medicine|
|Memphis, Tennessee, United States, 38103|
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jeffrey L. Blumer, Ph.D., M. D.||Rainbow Babies and Children's Hospital|