InsomniaPhase 1/2NCT00494468
Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Doses of Zolpidem in Children
A Phase 1/2 study testing Zolpidem in people with Insomnia and Sleep Disorder, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Insomnia, Sleep Disorder
- What is being tested?
- Zolpidem
- How many people
- 63 participants
- Where
- 11 sitesUnited States
- Study dates
- Oct 2002to Mar 2004
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Children's Hospital Research Foundation
Cincinnati, Ohio, 45229
Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Children's Hospital
Columbus, Ohio, 43205
National Jewish Medical and Research Center
Denver, Colorado, 80206
Texas Children's Hospital
Houston, Texas, 77030
Children's Mercy Hospital & Clinics
Kansas City, Missouri, 64108
University of California at San Diego
La Jolla, California, 92093
Arkansas Children's Hospital Research Center Inc.
Little Rock, Arkansas, 72202
University of Tennessee College of Medicine
Memphis, Tennessee, 38103
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Louisiana State University Health Sciences Center
Shreveport, Louisiana, 71103
About this study
Official title: Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Zolpidem Doses in Children Ages 2 to 18 Years of Age
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.
Read the 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.
- Conditions
- Insomnia, Sleep Disorder
- Being tested
- Zolpidem
- Keywords
- Insomnia, Sleep Disorder, Sleep Deprivation
- Medical subject headings
- Sleep Initiation and Maintenance Disorders, Sleep Wake Disorders, Sleep Deprivation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZolpidemDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2007 (estimated)
- Study startOct 2002
- Study completionMar 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InsomniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Collaborators
- Sanofi-Synthelabo
- Investigators
- Jeffrey L. Blumer, Ph.D., M. D., Principal investigator, Rainbow Babies and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00494468
- Sponsor's protocol ID
- PPRU-10590
- Status last verified
- Nov 2005
- First submitted
- 28 Jun 2007
- Last updated
- 29 Jun 2007
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Dose Pharmacokinetic and Pharmacodynamic Evaluation of Three Different Zolpidem Doses in Children Ages 2 to 18 Years of Age
- ClinicalTrials.gov ID
- NCT00494468
- Acronym / sponsor ID
- PPRU-10590
- Conditions
- Insomnia, Sleep Disorder
- Keywords
- Insomnia, Sleep Disorder, Sleep Deprivation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Collaborators
- Sanofi-Synthelabo
- Study start
- Oct 2002
- Study completion
- Mar 2004
- First posted
- 29 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zolpidem | Drug | – |
Primary outcome
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.
1 secondary outcome
Secondary outcome pharmacokinetic outcome measures will include estimation of the apparent Zolpidem Vd/F and CI/F.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2007.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey L. Blumer, Ph.D., M. D. principal investigator
Rainbow Babies and Children's Hospital
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Zolpidem in people with Insomnia and Sleep Disorder, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety will be assessed by collection of reported adverse events or findings on physical examination or laboratory assessments.. The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2007.