search
Back to results

Extension Study of Asenapine [P06107 (NCT01244815)] for Pediatric Bipolar Disorder (P05898) (ADDRESS-98)

Primary Purpose

Bipolar Disorder

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Asenapine
Rescue medication
Sponsored by
Organon and Co
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder

Eligibility Criteria

10 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Completed study P06107 and demonstrated acceptable degree of compliance with medication, visits and other study requirements
  • Must be male or a female who is not of childbearing potential and is not sexually active or is using a medically accepted method of contraception; or female who is not pregnant, or not lactating.
  • Must have a caregiver or responsible person living with the participant who agrees to provide support to ensure compliance with treatment, visits, and protocol procedures

Exclusion Criteria:

  • Positive pregnancy test or intention to become pregnant during the study
  • At imminent risk of self-harm or harm to others
  • Under involuntary inpatient commitment
  • Known serological evidence of human immunodeficiency virus (HIV) antibody

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Asenapine/Asenapine

    Placebo/Asenapine

    Arm Description

    Participants treated with asenapine in base trial P06107, were first treated with open-label flavored asenapine 2.5 mg twice per day (BID), then up-titrated to 5 mg BID at day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks.

    Participants treated with placebo in base trial P06107, were first treated with open-label flavored asenapine 2.5 mg BID, then up-titrated to 5 mg BID at day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks.

    Outcomes

    Primary Outcome Measures

    Number of Participants Who Experienced Clinical or Laboratory Adverse Events
    A clinical or laboratory adverse event is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.

    Secondary Outcome Measures

    Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score
    The Y-MRS assesses the severity of manic episodes by assigning a severity rating to each of 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight). 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. The Y-MRS total score, observed cases (OC), the assessment closest to the scheduled assessment day within the allowed window, 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. Improvement in symptoms is represented by change from baseline values that are negative.
    Percentage of Participants Who Were Y-MRS Total Score Remitters (Y-MRS ≤12)
    The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC 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. A remitter is a participant with a Y-MRS total score of 12 or lower.
    Percentage of Participants Who Were Y-MRS Total Score Responders
    The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC 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. A Y-MRS responder experiences a 50% or more decrease from baseline in Y-MRS total score.
    Time to First Total Y-MRS 50% Response
    The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, ranging from 0-60, with higher scores indicating more severe symptoms. The time to 50% response is the number of days on treatment to achieve a 50% decrease from baseline in Y-MRS total score.
    Time to Failure to Maintain Response in Y-MRS Total Score
    The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, ranging from 0-60, with higher scores indicating more severe symptoms. The time to failure is the number of days from first achieving a 50% or more decrease from baseline in Y-MRS total score to the first subsequent day of a less than 50% decrease from baseline in Y-MRS total score.
    Change From Baseline in Clinical Global Impression Scale for Assessing Overall Bipolar Illness (CGI-BP Overall)
    The CGI-BP overall is a single value score OC for assessing overall bipolar illness, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative.
    Change From Baseline in Clinical Global Impression Scale for Assessing Depression (CGI-BP Depression)
    The CGI-BP depression is a single value score OC for assessing depression, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative.
    Change From Baseline in Clinical Global Impression Scale for Assessing Mania (CGI-BP Mania)
    The CGI-BP mania is a single value score OC for assessing mania, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative.
    Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score
    The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7, and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. Improvement in symptoms is represented by change from baseline values that are negative.
    Percentage of CDRS-R Responders
    The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. A CDRS-R responder experiences a 50% or more decrease from baseline in CDRS-R total score.
    Percentage of Participants With Emergent Depression Based on CDRS-R
    The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. Participants with a CDRS-R score of 40 or greater (whose baseline CDRS-R is less than 40) exhibit emergent depression, which is a strong indicator of the presence or potential for a major depressive disorder.
    Change From Baseline in Children's Global Assessment Scale (CGAS)
    CGAS is a scale with a possible range of 1 to 100, measuring psychological, social, and school functioning in children. Minimum scores, OC range from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). An improvement in function is represented by a change from baseline value that is positive.
    Percentage of Participants With a CGAS Score of Equal or Greater Than 70
    CGAS is a scale with a possible range of 1 to 100, measuring psychological, social, and school functioning in children. Minimum scores, OC range from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The percentage of participants with a score of 70 or greater, representing normal to superior social functioning, is shown.
    Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaires (PQ-LES-Q) Total Score
    PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant rates 15 items reflecting quality of life from the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., health, mood or feelings); item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant, OC is the sum of the rating assigned to each of the first 14 items, and ranges from 14 to 70, with a higher score indicating better quality of life. An improvement in quality of life is represented by change from baseline values that are positive.
    Change From Baseline in PQ-LES-Q Overall Score
    PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant rates 15 items reflecting quality of life from the previous week. Item 15, the PQ-LES-Q overall score, observed OC, is a global assessment of overall quality of life, and ranges from 1 to 5, with a higher score indicating better quality of life. An improvement in quality of life is represented by change from baseline values that are positive.

    Full Information

    First Posted
    May 5, 2011
    Last Updated
    February 7, 2022
    Sponsor
    Organon and Co
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT01349907
    Brief Title
    Extension Study of Asenapine [P06107 (NCT01244815)] for Pediatric Bipolar Disorder (P05898)
    Acronym
    ADDRESS-98
    Official Title
    A 50-Week Open-Label, Flexible-Dose Trial of Asenapine Extension Treatment to P06107 in Pediatric Subjects With Acute Manic or Mixed Episodes Associated With Bipolar I Disorder
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2022
    Overall Recruitment Status
    Completed
    Study Start Date
    June 16, 2011 (Actual)
    Primary Completion Date
    September 5, 2014 (Actual)
    Study Completion Date
    September 5, 2014 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Organon and Co

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study will investigate the safety and tolerability of a flexible dosing regimen of asenapine for the long-term treatment of manic or mixed episodes associated with bipolar disorder I in children and adolescents who completed study P06107.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Bipolar Disorder

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    322 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Asenapine/Asenapine
    Arm Type
    Experimental
    Arm Description
    Participants treated with asenapine in base trial P06107, were first treated with open-label flavored asenapine 2.5 mg twice per day (BID), then up-titrated to 5 mg BID at day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks.
    Arm Title
    Placebo/Asenapine
    Arm Type
    Experimental
    Arm Description
    Participants treated with placebo in base trial P06107, were first treated with open-label flavored asenapine 2.5 mg BID, then up-titrated to 5 mg BID at day 4, then up-titrated to 10 mg BID at Day 7. After Day 7, flexible dosing of asenapine was continued for up to 50 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Asenapine
    Other Intervention Name(s)
    SCH 900274, ORG 5222
    Intervention Description
    One flavored asenapine sublingual tablet (containing either 2.5, 5 or 10 mg asenapine) twice daily (BID), starting at 2.5 mg on Day 1 for three consecutive days. Normally on Day 4, the dose will increase to 5 mg BID beginning with the evening dose. Normally on Day 7, the dose will increase to 10 mg BID beginning with the evening dose. The dose may be up-titrated earlier than Days 4 and 7 at the investigator's discretion. Beginning on Day 8 (or after at least 1 day on 10 mg BID), asenapine dosing will be flexible (2.5, 5, or 10 mg BID) until up to Week 50.
    Intervention Type
    Drug
    Intervention Name(s)
    Rescue medication
    Intervention Description
    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 (i.e., lorazepam [up to 4 mg/day] or an equivalent dose of short-acting 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.
    Primary Outcome Measure Information:
    Title
    Number of Participants Who Experienced Clinical or Laboratory Adverse Events
    Description
    A clinical or laboratory adverse event is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
    Time Frame
    Baseline (Day 1) to 30 days after the last dose of study drug (up to approximately 54 weeks)
    Secondary Outcome Measure Information:
    Title
    Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score
    Description
    The Y-MRS assesses the severity of manic episodes by assigning a severity rating to each of 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight). 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. The Y-MRS total score, observed cases (OC), the assessment closest to the scheduled assessment day within the allowed window, 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. Improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame
    Baseline, Day 182 and Day 350
    Title
    Percentage of Participants Who Were Y-MRS Total Score Remitters (Y-MRS ≤12)
    Description
    The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC 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. A remitter is a participant with a Y-MRS total score of 12 or lower.
    Time Frame
    Up to Day 350
    Title
    Percentage of Participants Who Were Y-MRS Total Score Responders
    Description
    The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC 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. A Y-MRS responder experiences a 50% or more decrease from baseline in Y-MRS total score.
    Time Frame
    Up to Day 350
    Title
    Time to First Total Y-MRS 50% Response
    Description
    The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, ranging from 0-60, with higher scores indicating more severe symptoms. The time to 50% response is the number of days on treatment to achieve a 50% decrease from baseline in Y-MRS total score.
    Time Frame
    Up to Day 350
    Title
    Time to Failure to Maintain Response in Y-MRS Total Score
    Description
    The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. The Y-MRS total score, OC for each participant is the sum of the ratings for the 11 individual items, ranging from 0-60, with higher scores indicating more severe symptoms. The time to failure is the number of days from first achieving a 50% or more decrease from baseline in Y-MRS total score to the first subsequent day of a less than 50% decrease from baseline in Y-MRS total score.
    Time Frame
    Up to Day 350
    Title
    Change From Baseline in Clinical Global Impression Scale for Assessing Overall Bipolar Illness (CGI-BP Overall)
    Description
    The CGI-BP overall is a single value score OC for assessing overall bipolar illness, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame
    Baseline, Day 182 and Day 350
    Title
    Change From Baseline in Clinical Global Impression Scale for Assessing Depression (CGI-BP Depression)
    Description
    The CGI-BP depression is a single value score OC for assessing depression, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame
    Baseline, Day 182 and Day 350
    Title
    Change From Baseline in Clinical Global Impression Scale for Assessing Mania (CGI-BP Mania)
    Description
    The CGI-BP mania is a single value score OC for assessing mania, recorded on a 7-point scale ranging from 1 for normal/not ill, to 7 for very severely ill. An improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame
    Baseline, Day 182 and Day 350
    Title
    Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score
    Description
    The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7, and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. Improvement in symptoms is represented by change from baseline values that are negative.
    Time Frame
    Baseline, Day 182 and Day 350
    Title
    Percentage of CDRS-R Responders
    Description
    The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. A CDRS-R responder experiences a 50% or more decrease from baseline in CDRS-R total score.
    Time Frame
    Up to Day 350
    Title
    Percentage of Participants With Emergent Depression Based on CDRS-R
    Description
    The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. The CDRS-R total score, OC for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. Participants with a CDRS-R score of 40 or greater (whose baseline CDRS-R is less than 40) exhibit emergent depression, which is a strong indicator of the presence or potential for a major depressive disorder.
    Time Frame
    Up to Day 350
    Title
    Change From Baseline in Children's Global Assessment Scale (CGAS)
    Description
    CGAS is a scale with a possible range of 1 to 100, measuring psychological, social, and school functioning in children. Minimum scores, OC range from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). An improvement in function is represented by a change from baseline value that is positive.
    Time Frame
    Baseline, Day 182 and Day 350
    Title
    Percentage of Participants With a CGAS Score of Equal or Greater Than 70
    Description
    CGAS is a scale with a possible range of 1 to 100, measuring psychological, social, and school functioning in children. Minimum scores, OC range from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The percentage of participants with a score of 70 or greater, representing normal to superior social functioning, is shown.
    Time Frame
    Up to Day 350
    Title
    Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaires (PQ-LES-Q) Total Score
    Description
    PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant rates 15 items reflecting quality of life from the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., health, mood or feelings); item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant, OC is the sum of the rating assigned to each of the first 14 items, and ranges from 14 to 70, with a higher score indicating better quality of life. An improvement in quality of life is represented by change from baseline values that are positive.
    Time Frame
    Baseline, Day 182 and Day 350
    Title
    Change From Baseline in PQ-LES-Q Overall Score
    Description
    PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant rates 15 items reflecting quality of life from the previous week. Item 15, the PQ-LES-Q overall score, observed OC, is a global assessment of overall quality of life, and ranges from 1 to 5, with a higher score indicating better quality of life. An improvement in quality of life is represented by change from baseline values that are positive.
    Time Frame
    Baseline, Day 182 and Day 350

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    10 Years
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Completed study P06107 and demonstrated acceptable degree of compliance with medication, visits and other study requirements Must be male or a female who is not of childbearing potential and is not sexually active or is using a medically accepted method of contraception; or female who is not pregnant, or not lactating. Must have a caregiver or responsible person living with the participant who agrees to provide support to ensure compliance with treatment, visits, and protocol procedures Exclusion Criteria: Positive pregnancy test or intention to become pregnant during the study At imminent risk of self-harm or harm to others Under involuntary inpatient commitment Known serological evidence of human immunodeficiency virus (HIV) antibody
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    26598478
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    27461426
    Citation
    Findling RL, Landbloom RL, Mackle M, Wu X, Snow-Adami L, Chang K, Durgam S. Long-term Safety of Asenapine in Pediatric Patients Diagnosed With Bipolar I Disorder: A 50-Week Open-Label, Flexible-Dose Trial. Paediatr Drugs. 2016 Oct;18(5):367-78. doi: 10.1007/s40272-016-0184-2.
    Results Reference
    derived

    Learn more about this trial

    Extension Study of Asenapine [P06107 (NCT01244815)] for Pediatric Bipolar Disorder (P05898)

    We'll reach out to this number within 24 hrs