Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder (P06107 Has an Extension [P05898; NCT01349907])(P06107)

NCT01244815 | Completed Phase 3 Results DMC

• 1 other identifier: P06107
• Study Type: interventional
• Target: 404
• Locations: 0 countries
• Sites: N/A

Brief Summary

Efficacy and safety of asenapine for the treatment of bipolar I disorder (manic or mixed episodes) will be evaluated in participants between 10 and 17 years old, who are either hospitalized or non-hospitalized. In this 3-weeks, double-blind, parallel design trial, eligible participants will be randomized to receive one out of three fixed dose levels of asenapine, or placebo. The study primary hypothesis is that at least one asenapine dose is superior to placebo as measured by the change from baseline to Day 21 in Young Mania Rating Scale (Y-MRS) total score. Trial medication and placebo are provided as identical-looking sublingual tablets; concurrent use of psychotropics is prohibited, except use of short-acting benzodiazepines and psychostimulants approved for the treatment of attention deficit hyperactivity disorder (ADHD). Main treatment effect is measured using Y-MRS and safety is evaluated using the recordings of adverse events, routine blood panels, physical examinations (including vital signs), and electrocardiograms. Participants who complete the double blind trial may be offered to continue (open-label) treatment with asenapine for an extended period of time. Follow-up information on safety parameters will be collected in all participants within 30 days following treatment discontinuation.

Conditions

Bipolar Disorder, Pediatric

Keywords

Bi-polar I disorder; antipsychotic; serotonin; dopamine; noradrenalin; histamine; pediatric

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Y-MRS Total Score at Day 21

  The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.

  Baseline and Day 21

Secondary Outcomes (16)

• Change From Baseline in Clinical Global Impression Scale for Use in Bipolar Disorder (CGI-BP) Overall Score at Day 21

  Baseline and Day 21

• Total Y-MRS 50% Responders at Days 4, 7, 14 and 21

  Baseline and Days 4, 7, 14 and 21

• Change From Baseline in CGI-BP Mania Score at Day 4

  Baseline and Day 4

• Change From Baseline in CGI-BP Mania Score at Day 7

  Baseline and Day 7

• Change From Baseline in CGI-BP Mania Score at Day 14

  Baseline and Day 14

Study Arms (4)

Asenapine 2.5 mg twice daily (BID)

EXPERIMENTAL

Participants receive asenapine 2.5 mg BID for 21 days.

Drug: asenapine; Drug: Rescue medication

Asenapine 5.0 mg BID

EXPERIMENTAL

Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.

Drug: asenapine; Drug: Rescue medication

Asenapine 10.0 mg BID

EXPERIMENTAL

Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.

Drug: asenapine; Drug: Rescue medication

Placebo

PLACEBO COMPARATOR

Participants receive placebo BID for 21 days.

Drug: Placebo to match asenapine; Drug: Rescue medication

Interventions

asenapine DRUG

Asenapine tablets, administered sublingually twice daily at one of three dose levels (2.5 mg, 5.0 mg, or 10.0 mg)

Also known as: SCH 900274, Saphris

Asenapine 10.0 mg BID; Asenapine 2.5 mg twice daily (BID); Asenapine 5.0 mg BID

Placebo to match asenapine DRUG

Placebo tablets to match asenapine tablets, administered sublingually twice daily

Placebo

Rescue medication DRUG

For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines and EPS medications (i.e., anticholinergics) are allowed. Benadryl (diphenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.

Asenapine 10.0 mg BID; Asenapine 2.5 mg twice daily (BID); Asenapine 5.0 mg BID; Placebo

Eligibility Criteria

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

You may qualify if:

• Participants who (or whose parent/legal representative) are able to give written informed consent.
• Participants must be 10 years of age or older and 17 years of age or younger at the time of treatment assignment (randomization).
• Participants must have a diagnosis of bipolar I disorder, confirmed by structured interview at screening.
• Participants must not be pregnant or lactating, and those who are sexually active or become sexually active during the trial, and of child-bearing potential, must be using a medically accepted form of birth control.
• Participants will be required to have stopped taking certain psycho-active medications prior to baseline.
• Participants must have a caregiver, or other responsible person living with them who agrees to provide support to the participant to ensure study and procedure compliance.

You may not qualify if:

• Diagnosis of bipolar II disorder, or other form of bipolar or psychotic disorder.
• Known or suspected mental retardation.
• Substance abuse, or dependence, within the past 6 months.
• There is risk of self-harm or harm to others.
• There is a history of tardive dyskinesia or dystonia.
• Pregnancy or lactation during the study.
• History of seizure disorder.
• Participation in any other clinical trial at the same time.
• A family member who is part of the study staff or is directly involved with the study.
• Other medical conditions determined by the study staff to possibly interfere with the study safety and efficacy evaluations.

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• Findling RL, Landbloom RL, Szegedi A, Koppenhaver J, Braat S, Zhu Q, Mackle M, Chang K, Mathews M. Asenapine for the Acute Treatment of Pediatric Manic or Mixed Episode of Bipolar I Disorder. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):1032-41. doi: 10.1016/j.jaac.2015.09.007. Epub 2015 Oct 24.

  PMID: 26598478 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

asenapine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood 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

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2010
• First Posted: November 19, 2010
• Study Start: June 16, 2011
• Primary Completion: August 28, 2013
• Study Completion: September 17, 2013
• Last Updated: June 20, 2024
• Results First Posted: September 4, 2014

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share