The purpose of this study is to determine the Pharmacokinetic profile, safety, and
tolerability of ramelteon in adolescent subjects with insomnia and gender- and race-matched
healthy adult subjects.
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.
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. These profiles
will be compared with those of healthy adult subjects aged 18 to 50 years who are matched by
race and gender, all 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.
Inclusion Criteria:
Inclusion criteria for adolescent subjects only:
- 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.
- 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.
- There is agreement in the participant's parent or caregiver's opinion with the
following:
- The complaint involves significant difficulty in initiating sleep
- 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 subjects only:
- Weighs at least 50 kg (110 pounds) and has a Screening body mass index between 18 and
30 kg/m2, inclusive.
Inclusion criteria for all subjects:
- Females of childbearing 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 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.
Exclusion Criteria:
- 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, hematocrit, 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.
- 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
mellitis, 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.
- 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, ECG, or clinical laboratory tests, as determined by the
investigator. Subjects 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.
- Is required to take or intends to continue taking any disallowed medication, any
prescription medication, herbal treatment or over-the counter medication that may
interfere with evaluation of the study medication, including:
- Anxiolytics
- muscle relaxants
- hypnotics
- Over-the-counter and prescription diet aids
- antidepressants
- narcotic analgesics
- anticonvulsants
- beta blockers
- sedating H1 antihistamines
- systemic steroids
- ginseng
- kava kava
- respiratory stimulants
- ginkgo biloba
- melatonin
- decongestants
- modafinil
- antipsychotics
- coumadin
- heparin
- potent CYP enzyme inhibitors such as ketoconazole, fluconazole and gemfibrozil
- potent CYP enzyme inducers such as rifampin, carbamazepine and St. John's wort.
Takeda Study Registration Call Center, Phone: 800-778-2860, Email: medicalinformation@tpna.com
