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

NCT00914862 | Completed Phase 1 Results

• 2 other identifiers: TAK-375_110U1111-1112-5188
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Insomnia

Keywords

Sleep Initiation and Maintenance Disorders; Drug Therapy

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

• 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.

  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.

• 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.

  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.

• 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).

  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.

• 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\[0-inf\]).

  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.

• 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.

  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.

• 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).

  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.

• 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).

  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)

• Number of Participants With Adverse Events (AE)

  Day 1 to Day 15

• Number of Participants With Clinically Significant Laboratory Findings

  Screening, Day 1, Day 2 and Day 4

• Number of Participants With Clinically Significant Vital Signs

  Screening, Day 1, Day 2 and Day 4

• Number of Participants With Clinically Significant Electrocardiogram Findings

  Screening, Day 2 and Day 4

• Number of Participants With Clinically Significant Physical Examination Results

  Screening, Day 1, Day 2 and Day 4

Study Arms (5)

Children Ramelteon 4 mg

EXPERIMENTAL

Children 6 to 11 years of age who had insomnia associated with ADHD received a single 4 mg oral dose of ramelteon.

Drug: Ramelteon

Children Ramelteon 8 mg

EXPERIMENTAL

Children 6 to 11 years of age who had insomnia associated with ADHD received a single oral 8 mg dose of ramelteon.

Drug: Ramelteon

Adolescents Ramelteon 4 mg

EXPERIMENTAL

Adolescents 12 to 17 years of age with insomnia received a single oral dose of 4 mg ramelteon.

Drug: Ramelteon

Adolescents Ramelteon 8 mg

EXPERIMENTAL

Adolescents 12 to 17 years of age with insomnia received a single oral dose of 8 mg ramelteon.

Drug: Ramelteon

Healthy Adult Ramelteon 8 mg

ACTIVE COMPARATOR

Healthy adults (18 to 50 years old) received a single oral dose of 8 mg ramelteon.

Drug: Ramelteon

Interventions

Ramelteon DRUG

Ramelteon tablets, orally for one day only.

Also known as: TAK-375, Rozerem

Adolescents Ramelteon 4 mg; Adolescents Ramelteon 8 mg; Children Ramelteon 4 mg; Children Ramelteon 8 mg; Healthy Adult Ramelteon 8 mg

Eligibility Criteria

• Age: 6 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (2)

Unknown Facility

Overland Park, Kansas, United States

Location

Unknown Facility

Kalamazoo, Michigan, United States

Location

Related Links

• Rozerem Package Insert

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

ramelteon

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Results Point of Contact

• Title: Sr. VP, Clinical Science
• Organization: Takeda Global Research and Development Center, Inc.

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2009
• First Posted: June 5, 2009
• Study Start: November 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: April 1, 2011
• Last Updated: April 4, 2012
• Results First Posted: April 4, 2012

Record last verified: 2012-03

Locations

US (2)