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

Bipolar Disorder Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01349907
• Other study ID #: P05898
• Secondary ID: MK-8274-022
• Status: Completed
• Phase: Phase 3
• Start date: June 16, 2011
• Est. completion date: September 5, 2014

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 322
• Est. completion date: September 5, 2014
• Est. primary completion date: September 5, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

References & 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. do — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline (Day 1) to 30 days after the last dose of study drug (up to approximately 54 weeks)
Secondary	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.	Baseline, Day 182 and Day 350
Secondary	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.	Up to Day 350
Secondary	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.	Up to Day 350
Secondary	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.	Up to Day 350
Secondary	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.	Up to Day 350
Secondary	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.	Baseline, Day 182 and Day 350
Secondary	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.	Baseline, Day 182 and Day 350
Secondary	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.	Baseline, Day 182 and Day 350
Secondary	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.	Baseline, Day 182 and Day 350
Secondary	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.	Up to Day 350
Secondary	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.	Up to Day 350
Secondary	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.	Baseline, Day 182 and Day 350
Secondary	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.	Up to Day 350
Secondary	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.	Baseline, Day 182 and Day 350
Secondary	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.	Baseline, Day 182 and Day 350