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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01349907
First received: May 5, 2011
Last updated: February 24, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention Phase
Bipolar Disorder
Drug: Asenapine
Drug: Rescue medication
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Who Experienced Clinical or Laboratory Adverse Events [ Time Frame: Baseline (Day 1) to 30 days after the last dose of study drug (up to approximately 54 weeks) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline, Day 182 and Day 350 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 350 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Day 182 and Day 350 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Day 182 and Day 350 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Day 182 and Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 182 and Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 350 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Day 182 and Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 182 and Day 350 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 182 and Day 350 ] [ Designated as safety issue: No ]
    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.


Enrollment: 322
Study Start Date: June 2011
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Asenapine/Asenapine
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.
Drug: Asenapine
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.
Other Name: SCH 900274, ORG 5222
Drug: Rescue medication
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.
Experimental: Placebo/Asenapine
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.
Drug: Asenapine
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.
Other Name: SCH 900274, ORG 5222
Drug: Rescue medication
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.

  Eligibility

Ages Eligible for Study:   10 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01349907

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01349907     History of Changes
Other Study ID Numbers: P05898, MK-8274-022
Study First Received: May 5, 2011
Results First Received: February 24, 2015
Last Updated: February 24, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Asenapine
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on March 30, 2015