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

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01349907
• Collaborator: (none)
• Enrollment: 322
• Arms: 2
• Actual Duration (Months): 38.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Asenapine; Drug: Rescue medication	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 322 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: Jun 16, 2011
• Actual Primary Completion Date: Sep 5, 2014
• Actual Study Completion Date: Sep 5, 2014

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced Clinical or Laboratory Adverse Events [Baseline (Day 1) to 30 days after the last dose of study drug (up to approximately 54 weeks)]

   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

1. Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score [Baseline, Day 182 and Day 350]

   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.

2. Percentage of Participants Who Were Y-MRS Total Score Remitters (Y-MRS ≤12) [Up to Day 350]

   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.

3. Percentage of Participants Who Were Y-MRS Total Score Responders [Up to Day 350]

   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.

4. Time to First Total Y-MRS 50% Response [Up to Day 350]

   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.

5. Time to Failure to Maintain Response in Y-MRS Total Score [Up to Day 350]

   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.

6. Change From Baseline in Clinical Global Impression Scale for Assessing Overall Bipolar Illness (CGI-BP Overall) [Baseline, Day 182 and Day 350]

   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.

7. Change From Baseline in Clinical Global Impression Scale for Assessing Depression (CGI-BP Depression) [Baseline, Day 182 and Day 350]

   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.

8. Change From Baseline in Clinical Global Impression Scale for Assessing Mania (CGI-BP Mania) [Baseline, Day 182 and Day 350]

   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.

9. Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score [Baseline, Day 182 and Day 350]

   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.

10. Percentage of CDRS-R Responders [Up to Day 350]

    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.

11. Percentage of Participants With Emergent Depression Based on CDRS-R [Up to Day 350]

    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.

12. Change From Baseline in Children's Global Assessment Scale (CGAS) [Baseline, Day 182 and Day 350]

    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.

13. Percentage of Participants With a CGAS Score of Equal or Greater Than 70 [Up to Day 350]

    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.

14. Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaires (PQ-LES-Q) Total Score [Baseline, Day 182 and Day 350]

    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.

15. Change From Baseline in PQ-LES-Q Overall Score [Baseline, Day 182 and Day 350]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01349907
• Other Study ID Numbers: P05898; MK-8274-022
• First Posted: May 9, 2011
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Bipolar Disorder; Asenapine

Study Results

Participant Flow

Recruitment Details	Participants with a diagnosis of bipolar I disorder who completed the 3-week base trial P06107 (NCT01224485).

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine in base trial P06107, were first treated with open-label flavored asenapine 2.5 mg twice daily (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.
Period Title: Overall Study
STARTED	241	81
COMPLETED	102	38
NOT COMPLETED	139	43

Baseline Characteristics

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine	Total
Arm/Group Description	Participants treated with asenapine 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.	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.	Total of all reporting groups
Overall Participants	241	80	321
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	13.8 (2.0)	13.7 (2.0)	13.8 (2.0)
Sex: Female, Male (Count of Participants)
Female	113 46.9%	47 58.8%	160 49.8%
Male	128 53.1%	33 41.3%	161 50.2%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of trial medication, and were 17 years old or younger. One treated participant from the Placebo/Asenapine group, who was 18 years old, was excluded from this analysis.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	241	80
Number [Participants]	197 81.7%	74 92.5%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=112, 37)	-4.9 (7.8)	-13.0 (8.3)
Day 350 (n=45, 20)	-6.5 (10.5)	-15.2 (5.8)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n= 112, 37)	63.4 26.3%	83.8 104.8%
Day 350 (n = 45, 20)	75.6 31.4%	90.0 112.5%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n= 111, 37)	37.8 15.7%	64.9 81.1%
Day 350 (n=43, 20)	53.5 22.2%	80.0 100%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Median (95% Confidence Interval) [Days]	15.0	49.0

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment. Restricted to participants who were total Y-MRS 50% responders in base trial P06107.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	120	21
Median (95% Confidence Interval) [Days]	NA	194.0

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=113, 37)	-0.9 (1.0)	-1.8 (1.1)
Day 350 (n=46, 20)	-1.2 (1.3)	-2.4 (1.2)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=113, 37)	-0.5 (0.9)	-0.8 (1.2)
Day 350 (n=46, 20)	-0.4 (1.0)	-1.2 (1.3)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=113, 37)	-1.0 (1.0)	-1.9 (1.1)
Day 350 (n=46, 20)	-1.2 (1.3)	-2.3 (1.2)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=112, 37)	-1.4 (6.4)	-5.4 (7.5)
Day 350 (n=44, 20)	-1.1 (5.5)	-4.3 (6.6)

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=111, 37)	36.0 14.9%	56.8 71%
Day 350 (n=43, 20)	32.6 13.5%	65.0 81.3%

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=112, 37)	2.7 1.1%	0.0 0%
Day 350 (n=44, 20)	2.3 1%	5.0 6.3%

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=114, 37)	9.7 (10.1)	17.4 (9.9)
Day 350 (n=46, 20)	13.1 (13.6)	22.5 (8.0)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=114, 37)	55.3 22.9%	73.0 91.3%
Day 350 (n=46, 20)	73.9 30.7%	85.0 106.3%

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=111, 36)	1.0 (7.1)	4.4 (8.3)
Day 350 (n=45, 20)	0.5 (7.3)	3.4 (10.9)

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants 17 years old or younger, who have taken at least one dose of trial medication, and have a baseline, and at least one post-baseline Y-MRS assessment.

Arm/Group Title	Asenapine/Asenapine	Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.	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.
Measure Participants	227	72
Day 182 (n=111, 36)	0.1 (0.8)	0.3 (0.8)
Day 350 (n=45, 20)	0.4 (1.0)	0.3 (0.9)

Adverse Events

Time Frame	30 days after the last dose of study drug (up to approximately 54 weeks).
Adverse Event Reporting Description	All enrolled and treated participants
Arm/Group Title	Asenapine/Asenapine		Placebo/Asenapine
Arm/Group Description	Participants treated with asenapine 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.		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.
All Cause Mortality
	Asenapine/Asenapine		Placebo/Asenapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Asenapine/Asenapine		Placebo/Asenapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/241 (7.1%)		6/81 (7.4%)
Gastrointestinal disorders
Swollen tongue	0/241 (0%)	0	1/81 (1.2%)	2
Immune system disorders
Drug hypersensitivity	0/241 (0%)	0	1/81 (1.2%)	2
Injury, poisoning and procedural complications
Accidental overdose	1/241 (0.4%)	1	0/81 (0%)	0
Intentional overdose	1/241 (0.4%)	1	0/81 (0%)	0
Nervous system disorders
Dystonia	1/241 (0.4%)	1	0/81 (0%)	0
Loss of consciousness	1/241 (0.4%)	1	0/81 (0%)	0
Somnolence	1/241 (0.4%)	1	0/81 (0%)	0
Psychiatric disorders
Aggression	2/241 (0.8%)	2	1/81 (1.2%)	2
Agitation	1/241 (0.4%)	1	1/81 (1.2%)	1
Anxiety	1/241 (0.4%)	1	0/81 (0%)	0
Bipolar disorder	2/241 (0.8%)	3	2/81 (2.5%)	2
Depression	3/241 (1.2%)	3	0/81 (0%)	0
Disturbance in social behaviour	1/241 (0.4%)	1	0/81 (0%)	0
Exhibitionism	1/241 (0.4%)	1	0/81 (0%)	0
Impulsive behaviour	1/241 (0.4%)	1	0/81 (0%)	0
Mania	1/241 (0.4%)	1	0/81 (0%)	0
Self-injurious ideation	1/241 (0.4%)	1	0/81 (0%)	0
Suicidal behaviour	1/241 (0.4%)	1	0/81 (0%)	0
Suicidal ideation	7/241 (2.9%)	8	1/81 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Asenapine/Asenapine		Placebo/Asenapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	135/241 (56%)		65/81 (80.2%)
Gastrointestinal disorders
Abdominal pain upper	10/241 (4.1%)	15	6/81 (7.4%)	6
Hypoaesthesia oral	2/241 (0.8%)	2	11/81 (13.6%)	11
Nausea	15/241 (6.2%)	17	9/81 (11.1%)	9
Paraesthesia oral	3/241 (1.2%)	3	8/81 (9.9%)	10
Vomiting	16/241 (6.6%)	18	4/81 (4.9%)	4
General disorders
Fatigue	15/241 (6.2%)	17	6/81 (7.4%)	7
Infections and infestations
Gastroenteritis viral	4/241 (1.7%)	4	5/81 (6.2%)	5
Investigations
Weight increased	42/241 (17.4%)	43	16/81 (19.8%)	16
Metabolism and nutrition disorders
Increased appetite	16/241 (6.6%)	18	6/81 (7.4%)	6
Nervous system disorders
Dizziness	5/241 (2.1%)	6	8/81 (9.9%)	10
Dysgeusia	4/241 (1.7%)	4	5/81 (6.2%)	5
Headache	21/241 (8.7%)	30	11/81 (13.6%)	21
Sedation	23/241 (9.5%)	29	19/81 (23.5%)	27
Somnolence	44/241 (18.3%)	50	29/81 (35.8%)	36

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No publication or manuscript shall contain any trade secret information of the sponsor or any proprietary or confidential information of the sponsor, and shall be confined to new discoveries and interpretations of scientific fact.