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InsomniaPhase 1NCT00914862

Pharmacokinetic and Safety of Ramelteon Between Adolescents With Insomnia and Healthy Adults

A Phase 1 study testing Ramelteon in people with Insomnia, run by Takeda at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the pharmacokinetic profile, safety, and tolerability of ramelteon in adolescents with insomnia, children with Attention Deficit Hyperactivity Disorder (ADHD) associated with insomnia and gender- and race-matched healthy adults. Read more about this study

Who is it for?
Ages 6 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Insomnia
What is being tested?
Ramelteon
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
2 sitesUnited States
Study dates
Nov 2009to Apr 2011
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 6 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • Inclusion criteria for adolescent and pediatric participants only:
  • Is male or female between 12 and 17 years of age (less than 18 years of age on Day 1) with complaints of insomnia characterized by difficulty with sleep initiation OR a male or female between 6 to 11 years of age (less than 12 years of age on Day 1) with complaints of insomnia characterized by difficulty with sleep initiation associated with ADHD.
  • Has a body mass index within the 5th to 95th percentile of the appropriate body mass index designated charts based on stature-for-age and weight-for-age and by gender.
  • In the age group of 12 to 17 years, has a history of primary insomnia characterized by difficulty initiating sleep as defined by the Pharmacologic Management of Insomnia in Children and Adolescents: Consensus Statement OR in the age group of 6 to 11 years, has a history of insomnia characterized by difficulty with sleep initiation (as defined by the Pharmacologic Management of Insomnia in Children and Adolescents: Consensus Statement associated with ADHD).
  • There is agreement in the participant's parent or caregiver's opinion with the following:
  • The complaint involves significant difficulty in initiating sleep
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  • The sleep disturbance does not occur exclusively during the course of narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, or parasomnia.
  • The disturbance does not occur exclusively during the course of another mental disorder (eg, Major Depressive Disorder, Generalized Anxiety Disorder, and Delirium).
  • The disturbance is not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition.
  • Based on sleep history, reports a subjective sleep latency greater than or equal to 45 minutes for at least 1 month.
  • If taking concomitant medications, he/she has been on a stable dose or regimen of his/her medication for at least 30 days prior to Screening.
  • Inclusion criteria for gender- and race-matched adult participants only:
  • Weighs at least 50 kg (110 pounds) and has a Screening body mass index between 18 and 30 kg/m^2, inclusive.
  • A female of childbearing potential (defined as females aged ≥12 years old and younger girls who, at the discretion of the investigator, are deemed to be of reproductive potential) and males who are sexually active agree to routinely use adequate contraception from Screening throughout the duration of the study and through 30 days following the last dose of study medication.
  • Must have a negative urine test result for selected substances of abuse (including alcohol) at Screening and Day 1.
  • Has clinical laboratory results (including clinical chemistry, hematology, and complete urinalysis [fasted] within the reference range for the testing laboratory unless the results are deemed not clinically meaningful by the investigator or sponsor.
  • Has a negative test result for hepatitis B surface antigen and hepatitis C virus antibody, and no known history of human immunodeficiency virus.

Who cannot join

  • Is participating in another investigational study or has taken an investigational drug within 30 days (or 5 half-lives, whichever period is longer) prior to study Screening.
  • Has received ramelteon within 30 days of Screening.
  • Is a study site employee, or is an immediate family member (ie, spouse, parent, child, sibling) of a study site employee, involved in conduct of this study.
  • Has abnormal hematological parameters of hemoglobin and/or hematocrit (if these exceed +/- 2 points of the normal range for the age and sex appropriate values), or erythrocytes at Screening.
  • Has a known hypersensitivity to ramelteon or related compounds including melatonin.
  • Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as consumption of more than 4 alcoholic drinks per day) within 1 year prior to study Day 1.
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  • Has had an acute, clinically significant illness within 30 days prior to Screening.
  • Has autistic spectrum disorders or other pervasive developmental disorder.
  • Has a history or clinical manifestations of significant metabolic (including diabetes mellitus, hypercholesterolemia, or dyslipidemia), hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urologic, immunologic, musculoskeletal, or psychiatric disorder unless currently controlled and stable with protocol-allowed medication for at least 30 days prior to Screening (except for ADHD in the age group of 6 to 11 years).
  • Has sleep schedule changes required by employment, school and/or extra curricular activity (eg, shift worker) within 3 months prior to Screening, or has flown across greater than 3 time zones within 7 days prior to Screening.
  • Has a history or clinical manifestations of depression, seizures, sleep apnea, restless leg syndrome, or periodic leg movements during sleep.
  • Has a history of abdominal surgery (except laparoscopic cholecystectomy or uncomplicated appendectomy) or thoracic or nonperipheral vascular surgery within 6 months prior to study Day 1.
  • Has a history of cancer, other than basal cell carcinoma or Stage 1 squamous cell carcinoma of the skin that has not been in remission for at least 5 years prior to study Day 1.
  • Has used any tobacco (ie, nicotine) products (including but not limited to cigarettes, pipe, cigar, chewing tobacco, nicotine patch, or nicotine gum) within 6 weeks prior to Screening, or is unwilling to abstain from these products for the duration of the study.
  • Has poor peripheral venous access.
  • Has any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiography (ECG), or clinical laboratory tests, as determined by the investigator. Participants with clinically significant abnormalities being considered for the study must be approved by both Takeda medical monitor or designee and the Principal Investigator.
  • Has any additional condition(s) that in the Investigator's opinion would: a) affect sleep/wake function, b) prohibit from completing the study, or c) not be in the best interest of to participate in the study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Study site

    Kalamazoo, Michigan

  • Study site

    Overland Park, Kansas

Other trials in United States

About this study

Official title: A Comparative Single Dose Pharmacokinetic and Safety Study of 4 mg or 8 mg Ramelteon in Adolescents With Insomnia Characterized by Difficulty With Sleep Onset, Children With Insomnia Associated With ADHD, and Healthy Adults.

The purpose of this study is to determine the pharmacokinetic profile, safety, and tolerability of ramelteon in adolescents with insomnia, children with Attention Deficit Hyperactivity Disorder (ADHD) associated with insomnia and gender- and race-matched healthy adults.

Read the detailed description

Ramelteon is a treatment for insomnia approved for use in the United States (US) in July 2005 and in the Philippines and Indonesia in 2008. It is currently under development in the European Union (EU) and Japan. Ramelteon is marketed in the US as ROZEREM® for the treatment of insomnia characterized by difficulty with sleep onset in patients over 18 years of age.

In adolescents, the form of sleep onset and/or sleep maintenance insomnia, defined as psychophysiologic insomnia, is similar to adults, and more appropriate for treatment with pharmacological intervention when compared to insomnia in children younger than 12 years of age. In psychophysiologic insomnia, the individual develops conditioned anxiety around difficulty falling or staying asleep, which leads to heightened physiologic and emotional arousal and further compromises the ability to sleep. In children over the age of 12, insomnia is more likely to be persistent and have identifiable consequences. In addition, there is less variability in normative sleep data for this age group than in younger children.

Sleep disturbances are also common in children. Specifically, insomnia associated with ADHD in children is very common with a reported prevalence of 28% in medication-free children with ADHD.

This study is to characterize the pharmacokinetics (PK) and safety profile of a 4 or 8 mg dose of ramelteon in adolescents who are between 12 to 17 years of age (prior to the 18th birthday) with insomnia characterized by difficulty with sleep initiation, and in pediatrics who are between 6 to 11 years of age who have insomnia associated with ADHD. These profiles will be compared with those of healthy adults aged 18 to 50 years who are matched by race and gender receiving an 8 mg dose of ramelteon. This open-label study is designed in accordance with the recommendations of the FDA and ICH guidances for pediatric PK studies.

Conditions
Insomnia
Being tested
Ramelteon
Keywords
Sleep Initiation and Maintenance Disorders, Drug Therapy
Medical subject headings
Sleep Initiation and Maintenance Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RamelteonDrug

    Also called TAK-375, Rozerem

    Ramelteon tablets, orally for one day only.

Study groups in NCT00914862
Study groupRoleWhat they receive
Children Ramelteon 4 mgExperimentalChildren 6 to 11 years of age who had insomnia associated with ADHD received a single 4 mg oral dose of ramelteon.
Receives: Drug: Ramelteon
Children Ramelteon 8 mgExperimentalChildren 6 to 11 years of age who had insomnia associated with ADHD received a single oral 8 mg dose of ramelteon.
Receives: Drug: Ramelteon
Adolescents Ramelteon 4 mgExperimentalAdolescents 12 to 17 years of age with insomnia received a single oral dose of 4 mg ramelteon.
Receives: Drug: Ramelteon
Adolescents Ramelteon 8 mgExperimentalAdolescents 12 to 17 years of age with insomnia received a single oral dose of 8 mg ramelteon.
Receives: Drug: Ramelteon
Healthy Adult Ramelteon 8 mgActive comparatorHealthy adults (18 to 50 years old) received a single oral dose of 8 mg ramelteon.
Receives: Drug: Ramelteon

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Observed Serum Concentration (Cmax)

    Maximum observed serum concentration (Cmax) is the peak serum concentration of ramelteon and its metabolite (M-II) after administration, obtained directly from the serum concentration-time curve.

    Measured: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.

  2. Time to Reach Maximum Serum Concentration (Tmax)

    Tmax: Time to reach the maximum serum concentration (Cmax) of ramelteon and its metabolite M-II, equal to time (hours) to Cmax.

    Measured: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.

  3. Area Under the Serum Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc])

    Area under the serum concentration-time curve from time 0 to time of last quantifiable concentration (tlqc) of ramelteon and its metabolite M-II, calculated using the linear trapezoidal rule.

    Measured: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.

  4. Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC[0-inf])

    Area under the serum concentration-time curve from time zero extrapolated to infinity for ramelteon and its metabolite M-II. The terminal area from the last quantifiable concentration (lqc) to infinity is calculated by approximation: lqc / terminal elimination rate constant (λz).

    Measured: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.

  5. Apparent Clearance After Oral Administration (CL/F)

    Apparent oral clearance of drug from the serum calculated as:

    CL/F = Dose / Area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC[0-inf]).

    Measured: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.

  6. Terminal Elimination Rate Constant (λz)

    The rate at which ramelteon and its metabolite M-II are eliminated from the body, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase.

    Measured: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.

  7. Terminal Elimination Half-life (T1/2)

    Terminal phase elimination half-life (T1/2) for ramelteon and its metabolite M-II is the time required for half of the drug to be eliminated from the serum, calculated as T1/2 = natural logarithm of 2 (ln[2]) / Terminal elimination rate constant (λz).

    Measured: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.

  8. Apparent Volume of Distribution (Vz/F)

    Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as Vz/F = Apparent oral clearance (CL/F) / Terminal elimination rate constant (λz).

    Measured: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.

Secondary outcomes (5)
  1. Number of Participants With Adverse Events (AE)

    An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product; it did not necessarily have to have a causal relationship with this treatment. The different categories of intensity (severity) were characterized as follows:

    Mild: The event was transient and easily tolerated by the participant.

    Moderate: The event causes the participant discomfort and interrupted usual activities.

    Severe: The event causes considerable interference with the participant's usual activities.

    Measured: Day 1 to Day 15

  2. Number of Participants With Clinically Significant Laboratory Findings

    Laboratory samples were collected at Screening, Check-in (Day 1), and Day 2 or Early Termination for assessment of hematology, chemistry, and urinalysis.

    Measured: Screening, Day 1, Day 2 and Day 4

  3. Number of Participants With Clinically Significant Vital Signs

    Vital signs included oral body temperature, pulse and blood pressure (taken after 5 minutes in the sitting position). Vital signs measurements were determined to be clinically significant according to predefined criteria.

    Measured: Screening, Day 1, Day 2 and Day 4

  4. Number of Participants With Clinically Significant Electrocardiogram Findings

    A standard 12-lead electrocardiogram (ECG) was recorded at Screening, Day 2, and at Final Visit (Day 4). The investigator interpreted the ECG using one of the following categories: within normal limits, abnormal but not clinically significant, or abnormal and clinically significant.

    Measured: Screening, Day 2 and Day 4

  5. Number of Participants With Clinically Significant Physical Examination Results

    A complete physical examination was performed for each participant at Screening, Check-in (Day 1), Day 2, and Final Visit (Day 4) or Early Termination. The examination consisted of a review of the following body systems: eyes; ears, nose, and throat; respiratory; gastrointestinal; extremities; musculoskeletal; cardiovascular; nervous; and dermatological.

    Measured: Screening, Day 1, Day 2 and Day 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jun 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionMar 2011
  4. Study completionApr 2011

Resources

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
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00914862
Sponsor's protocol ID
TAK-375_110
Other IDs
U1111-1112-5188
Status last verified
Mar 2012
First submitted
3 Jun 2009
Last updated
4 Apr 2012
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ramelteon in people with Insomnia, run by Takeda at 2 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 17 inclusion and 17 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 4 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Observed Serum Concentration (Cmax) (time frame: Day 1: predose (within 1 hour prior to dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 16 hours post-dose.). The study lists 8 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 4 Apr 2012.

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