search
Back to results

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

Primary Purpose

Insomnia, Sleep Disorder

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Zolpidem
Sponsored by
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Insomnia focused on measuring Insomnia, Sleep Disorder, Sleep Deprivation

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female between the ages of 2 years and 18 years.
  2. 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.
  3. 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.

  4. 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.

Exclusion Criteria:

  1. Pregnancy and/or breastfeeding;
  2. 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;
  3. Elevations in screening blood tests of renal (SCr) and liver (ALT, AST and/or bilirubin) > 2 times the upper limit of normal for age.
  4. 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.
  5. 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.
  6. Currently using any systemic contraceptive steroids including: oral contraceptives, transdermal patch, vaginal insert, levonorgestrel implant and medroxyprogesterone acetate contraceptive injection.

Sites / Locations

  • Arkansas Children's Hospital Research Center Inc.
  • University of California at San Diego
  • National Jewish Medical and Research Center
  • Louisiana State University Health Sciences Center
  • Children's Mercy Hospital & Clinics
  • Children's Hospital Research Foundation
  • Rainbow Babies and Children's Hospital
  • Children's Hospital
  • The Children's Hospital of Philadelphia
  • University of Tennessee College of Medicine
  • Texas Children's Hospital

Outcomes

Primary Outcome Measures

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 Measures

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

Full Information

First Posted
June 28, 2007
Last Updated
June 28, 2007
Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
Sanofi-Synthelabo
search

1. Study Identification

Unique Protocol Identification Number
NCT00494468
Brief Title
Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Doses of Zolpidem in Children
Official Title
Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Zolpidem Doses in Children Ages 2 to 18 Years of Age
Study Type
Interventional

2. Study Status

Record Verification Date
November 2005
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2004 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
Sanofi-Synthelabo

4. Oversight

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insomnia, Sleep Disorder
Keywords
Insomnia, Sleep Disorder, Sleep Deprivation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
63 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zolpidem
Primary Outcome Measure Information:
Title
Safety will be assessed by collection of reported adverse events or findings on physical examination or laboratory assessments.
Title
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).
Title
Polysomnography, including an electroencephalogram, electrooculogram and electromyogram will be performed on two occasions and represents the primary pharmacodynamic outcome assessment for this study.
Title
Measures will include:
Title
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
Title
Sleep Latencies; sleep onset latency, Rapid Eye Movement, (REM) latency, slow-wave sleep,(SWS) latency
Title
Sleep Stages (as absolute and relative proportions thereof: sleep stages I, II, III and IV; sleep stage REM; stage awake
Title
Non-Rem/REM Cycle Parameters: duration of the cycles, REM sleep per cycle, SWS sleep per cycle, number of cycles;
Title
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 Measure Information:
Title
Secondary outcome pharmacokinetic outcome measures will include estimation of the apparent Zolpidem Vd/F and CI/F.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey L. Blumer, Ph.D., M. D.
Organizational Affiliation
Rainbow Babies and Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arkansas Children's Hospital Research Center Inc.
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
University of California at San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
National Jewish Medical and Research Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Louisiana State University Health Sciences Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
Children's Mercy Hospital & Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Children's Hospital Research Foundation
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Tennessee College of Medicine
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs