A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Sublingual Asenapine in a Pediatric Population With Schizophrenia or Bipolar I Disorder (P06522 AM1)

NCT01206517 | Completed Phase 1 Results

• 1 other identifier: P06522
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is an open label, sequential-group, two site, multiple dose escalating study of sublingual administered asenapine in a pediatric population with schizophrenia or bipolar I disorder; in one study cohort (3a) participants with other conditions treatable with chronic antipsychotic medication can also be enrolled. Participants will receive a single sublingual placebo dose on Day -1, followed by multiple sublingual doses of asenapine twice daily (b.i.d.) for 6 days (Cohorts 1 and 2), 7 days (Cohort 3b-d), or 11 days (Cohort 3a), and a final once daily administration on Day 7 (Cohorts 1 and 2), Day 8 (Cohort 3b-d) or Day 12 (Cohort 3a).

Conditions

Schizophrenia; Bipolar I Disorder

Keywords

asenapine; pediatric schizophrenia; bipolar I disorder

Outcome Measures

Primary Outcomes (4)

• Maximum Plasma Concentration (Cmax) of Asenapine

  Cmax is the peak plasma concentration following a dose of the study drug.

  Predose (0 hours) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 36 and 48 hours after the final asenapine dose (administered on Day 7 for Cohorts 1 and 2; on Day 8 for Cohorts 3b, 3c and 3d; and on Day 12 for Cohort 3a)

• Time to Maximum Plasma Concentration (Tmax) of Asenapine

  tmax is the time from dosing to maximum plasma drug concentration levels.

  Predose (0 hours) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 36 and 48 hours after the final asenapine dose (administered on Day 7 for Cohorts 1 and 2; on Day 8 for Cohorts 3b, 3c and 3d; and on Day 12 for Cohort 3a)

• Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post Dose (AUC0-12) of Asenapine

  AUC0-12 is the area under the plasma drug-concentration time curve calculated for the 12 hour interval after dosing.

  Predose (0 hours) and 0.5, 1, 1.5, 2, 3, 4, 6 and 12 hours after the final asenapine dose (administered on Day 7 for Cohorts 1 and 2; on Day 8 for Cohorts 3b, 3c and 3d; and on Day 12 for Cohort 3a)

• Terminal Phase (Elimination) Half-life (t1/2) of Asenapine

  Elimination t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase.

  Predose (0 hours) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 36 and 48 hours after the final asenapine dose (administered on Day 7 for Cohorts 1 and 2; on Day 8 for Cohorts 3b, 3c and 3d; and on Day 12 for Cohort 3a)

Study Arms (3)

Cohort 1

EXPERIMENTAL

Participants 10 or 11 years of age

Drug: Asenapine 2.5 mg

Cohort 2

EXPERIMENTAL

Participants 10 or 11 years of age

Drug: Asenapine 5 mg

Cohort 3a-d

EXPERIMENTAL

Cohort 3a: Participants 10 or 11 years of age Cohort 3b: Participants 12 or 13 years of age Cohort 3c: Participants 14 or 15 years of age Cohort 3d: Participants 16 or 17 years of age

Drug: Asenapine 10 mg

Interventions

Asenapine 2.5 mg DRUG

Asenapine tablet, sublingually (SL), 2.5 mg b.i.d. on Days 1-6 and one 2.5 mg tablet, SL, on Day 7.

Also known as: SCH 900274, Org 5222

Cohort 1

Asenapine 5 mg DRUG

Asenapine tablet, SL, 5 mg b.i.d. on Days 1-6 and one 5 mg tablet, SL, on Day 7.

Also known as: SCH 900274, Org 5222

Cohort 2

Asenapine 10 mg DRUG

Asenapine tablets, SL, in a rising dose schedule to 10 mg b.i.d. (with a single 10 mg dose on final day). For Cohorts 3b, 3c and 3d, rising dose schedule begins with asenapine 5 mg b.i.d. on Day 1 and dosing occurs through Day 8. For Cohort 3a, rising dose schedule begins with asenapine 2.5 mg b.i.d. on Day 1 and dosing occurs through Day 12.

Also known as: SCH 900274, Org 5222

Cohort 3a-d

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• For participants in Cohorts 1, 2, 3b, 3c and 3d:
• Diagnosis of schizophrenia or bipolar I disorder
• A schizophrenic participant must have a diagnosis of current schizophrenia of paranoid disorganized, catatonic, or undifferentiated subtype as determined by a structured clinical interview at screening
• A bipolar I disorder participant must have a primary diagnosis of bipolar I disorder, current episode manic, or mixed as determined by a structured clinical interview at screening
• For participants in Cohort 3a:
• Documented history of schizophrenia, bipolar disorder, autism, conduct disorder, oppositional defiant disorder, or any condition for which the chronic use of antipsychotic medication (e.g, risperidone, olanzapine, aripiprazole, haloperidol) was warranted and/or administered
• All participants:
• Must be at least 10 and not older than 17 years of age at the day of first asenapine dosing (Cohort 3); for Cohort 1 and 2 subjects should be at least 10 and not older than 11 years of age at the day of first asenapine dosing
• Must be able and willing to sign an informed assent as required by local regulations before study participation and able to adhere to dose and visit schedules or their parent/authorized legal representative(s) should be able and willing to sign an informed consent, and should be fluent in the language of the informed consent
• Must have a caregiver or an identified responsible person who is considered reliable by the investigator and who has agreed to provide support to the subject to ensure compliance with trial treatment, outpatient visits, and protocol procedures
• Must be fluent in the language of the investigator, trial staff (including raters) and the informed assent
• Must be willing to discontinue all psychotropic medication during the treatment period except for those specified in the protocol
• Have discontinued the use of strong inhibitors or inducers of cytochrome P450 (CYP)1A2 and/or CYP2D6 (e.g. fluvoxamine, citalopram, fluoxetine, paroxetine, omeprazole, and rifampicin) and beta-blockers, applying a washout period of 5 half lives or 7 days, whichever is longer, AND be stabilized on non-interacting alternative medication (i.e. medication not interacting with asenapine pharmacokinetics) for 2 weeks prior to baseline if their medical condition requires this
• Clinical laboratory tests (complete blood count \[CBC\], blood chemistry, and urinalysis) must be within normal limits or clinically acceptable to the investigator, after discussion with the Sponsor and following agreement of the Sponsor's medical monitor
• Screening 12 lead electrocardiogram (ECG) conduction intervals and vital signs recordings (oral body temperature, systolic/diastolic blood pressure and pulse rate) must be clinically acceptable according to the investigator, after discussion with the Sponsor and following agreement of the Sponsor's medical monitor

You may not qualify if:

• The participant will be excluded from entry if ANY of the criteria listed below are met at baseline
• The participant:
• Is pregnant, intends to become pregnant (within 3 months of ending the study), or is breastfeeding
• In the opinion of the investigator, will not be able to participate optimally in the study
• Has an uncontrolled, unstable clinically significant medical condition (e.g., renal, endocrine, hepatic, respiratory, cardiovascular, hematologic, immunologic, gastrointestinal or cerebrovascular disease, or malignancy) that may interfere with the interpretation of pharmacokinetic, safety and tolerability evaluations in the opinion of the investigator
• Has a history of any infectious disease within 4 weeks prior to drug administration that in the opinion of the investigator, affects the subject's ability to participate in the trial
• Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
• Has a positive screen for drugs with a high potential for abuse (during the Screening period or clinical conduct of the trial)
• Has a history of psychiatric or personality disorders that in the opinion of the investigator and sponsor, affects the subject's ability to participate in the trial
• Has a history of neuroleptic malignant syndrome
• Has a diagnosis of mental retardation or organic brain disorder
• Has a diagnosis of psychotic disorder or a behavioral disturbance thought to be substance induced or due to substance abuse
• Has a current (past 6 months) substance and alcohol abuse or dependence (excluding nicotine and caffeine)
• Has a history of tardive dyskinesia or tardive dystonia
• If has attention-deficit/hyperactivity disorder (ADHD), has not been on a stable dose of stimulants (e.g. amphetamines, methylphenidate) for the last 3 months (participants who have not taken any stimulants in the last month will not be excluded)

Sponsors & Collaborators

• Organon and Co: lead

MeSH Terms

Conditions

Schizophrenia

Interventions

asenapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 17, 2010
• First Posted: September 22, 2010
• Study Start: July 18, 2010
• Primary Completion: August 4, 2011
• Study Completion: August 4, 2011
• Last Updated: May 23, 2024
• Results First Posted: December 21, 2012

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share