Trial Outcomes & Findings for Extension Study of Asenapine [P06107 (NCT01244815)] for Pediatric Bipolar Disorder (P05898) (NCT NCT01349907)

NCT ID: NCT01349907

Last Updated: 2024-05-22

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 322 participants
• Primary outcome timeframe: Baseline (Day 1) to 30 days after the last dose of study drug (up to approximately 54 weeks)
• Results posted on: 2024-05-22

Participant Flow

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

Participant milestones

Measure	Asenapine/Asenapine 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.	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.
Overall Study STARTED	241	81
Overall Study COMPLETED	102	38
Overall Study NOT COMPLETED	139	43

Reasons for withdrawal

Measure	Asenapine/Asenapine 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.	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.
Overall Study Adverse Event	37	11
Overall Study Treatment failure	13	4
Overall Study Lost to Follow-up	25	6
Overall Study Withdrawal by Subject	30	8
Overall Study Protocol Violation	33	13
Overall Study Administrative	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Asenapine/Asenapine n=241 Participants 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.	Placebo/Asenapine n=80 Participants 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 n=321 Participants Total of all reporting groups
Age, Continuous	13.8 Years STANDARD_DEVIATION 2.0 • n=5 Participants	13.7 Years STANDARD_DEVIATION 2.0 • n=7 Participants	13.8 Years STANDARD_DEVIATION 2.0 • n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants	47 Participants n=7 Participants	160 Participants n=5 Participants
Sex: Female, Male Male	128 Participants n=5 Participants	33 Participants n=7 Participants	161 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to 30 days after the last dose of study drug (up to approximately 54 weeks)

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=241 Participants 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.	Placebo/Asenapine n=80 Participants 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.
Number of Participants Who Experienced Clinical or Laboratory Adverse Events	197 Participants	74 Participants

SECONDARY outcome

Timeframe: Baseline, Day 182 and Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score Day 182 (n=112, 37)	-4.9 Score on a scale Standard Deviation 7.8	-13.0 Score on a scale Standard Deviation 8.3
Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score Day 350 (n=45, 20)	-6.5 Score on a scale Standard Deviation 10.5	-15.2 Score on a scale Standard Deviation 5.8

SECONDARY outcome

Timeframe: Up to Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Percentage of Participants Who Were Y-MRS Total Score Remitters (Y-MRS ≤12) Day 182 (n= 112, 37)	63.4 Percentage of participants	83.8 Percentage of participants
Percentage of Participants Who Were Y-MRS Total Score Remitters (Y-MRS ≤12) Day 350 (n = 45, 20)	75.6 Percentage of participants	90.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Percentage of Participants Who Were Y-MRS Total Score Responders Day 182 (n= 111, 37)	37.8 Percentage of participants	64.9 Percentage of participants
Percentage of Participants Who Were Y-MRS Total Score Responders Day 350 (n=43, 20)	53.5 Percentage of participants	80.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Time to First Total Y-MRS 50% Response	15.0 Days Interval 14.0 to 21.0	49.0 Days Interval 44.0 to 50.0

SECONDARY outcome

Timeframe: Up to Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=120 Participants 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.	Placebo/Asenapine n=21 Participants 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.
Time to Failure to Maintain Response in Y-MRS Total Score	NA Days Interval 268.0 to NA = Not achieved after 362 days of follow-up	194.0 Days Interval 78.0 to NA = Not achieved after 362 days of follow-up

SECONDARY outcome

Timeframe: Baseline, Day 182 and Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Change From Baseline in Clinical Global Impression Scale for Assessing Overall Bipolar Illness (CGI-BP Overall) Day 182 (n=113, 37)	-0.9 Score on a scale Standard Deviation 1.0	-1.8 Score on a scale Standard Deviation 1.1
Change From Baseline in Clinical Global Impression Scale for Assessing Overall Bipolar Illness (CGI-BP Overall) Day 350 (n=46, 20)	-1.2 Score on a scale Standard Deviation 1.3	-2.4 Score on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: Baseline, Day 182 and Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Change From Baseline in Clinical Global Impression Scale for Assessing Depression (CGI-BP Depression) Day 182 (n=113, 37)	-0.5 Score on a scale Standard Deviation 0.9	-0.8 Score on a scale Standard Deviation 1.2
Change From Baseline in Clinical Global Impression Scale for Assessing Depression (CGI-BP Depression) Day 350 (n=46, 20)	-0.4 Score on a scale Standard Deviation 1.0	-1.2 Score on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline, Day 182 and Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Change From Baseline in Clinical Global Impression Scale for Assessing Mania (CGI-BP Mania) Day 182 (n=113, 37)	-1.0 Score on a scale Standard Deviation 1.0	-1.9 Score on a scale Standard Deviation 1.1
Change From Baseline in Clinical Global Impression Scale for Assessing Mania (CGI-BP Mania) Day 350 (n=46, 20)	-1.2 Score on a scale Standard Deviation 1.3	-2.3 Score on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: Baseline, Day 182 and Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score Day 182 (n=112, 37)	-1.4 Score on a scale Standard Deviation 6.4	-5.4 Score on a scale Standard Deviation 7.5
Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score Day 350 (n=44, 20)	-1.1 Score on a scale Standard Deviation 5.5	-4.3 Score on a scale Standard Deviation 6.6

SECONDARY outcome

Timeframe: Up to Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Percentage of CDRS-R Responders Day 182 (n=111, 37)	36.0 Percentage of participants	56.8 Percentage of participants
Percentage of CDRS-R Responders Day 350 (n=43, 20)	32.6 Percentage of participants	65.0 Percentage of participants

SECONDARY outcome

Timeframe: Up to Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Percentage of Participants With Emergent Depression Based on CDRS-R Day 182 (n=112, 37)	2.7 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Emergent Depression Based on CDRS-R Day 350 (n=44, 20)	2.3 Percentage of participants	5.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 182 and Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Change From Baseline in Children's Global Assessment Scale (CGAS) Day 182 (n=114, 37)	9.7 Score on a scale Standard Deviation 10.1	17.4 Score on a scale Standard Deviation 9.9
Change From Baseline in Children's Global Assessment Scale (CGAS) Day 350 (n=46, 20)	13.1 Score on a scale Standard Deviation 13.6	22.5 Score on a scale Standard Deviation 8.0

SECONDARY outcome

Timeframe: Up to Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Percentage of Participants With a CGAS Score of Equal or Greater Than 70 Day 182 (n=114, 37)	55.3 Percentage of participants	73.0 Percentage of participants
Percentage of Participants With a CGAS Score of Equal or Greater Than 70 Day 350 (n=46, 20)	73.9 Percentage of participants	85.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 182 and Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaires (PQ-LES-Q) Total Score Day 182 (n=111, 36)	1.0 Score on a scale Standard Deviation 7.1	4.4 Score on a scale Standard Deviation 8.3
Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaires (PQ-LES-Q) Total Score Day 350 (n=45, 20)	0.5 Score on a scale Standard Deviation 7.3	3.4 Score on a scale Standard Deviation 10.9

SECONDARY outcome

Timeframe: Baseline, Day 182 and Day 350

Population: 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.

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.

Outcome measures

Measure	Asenapine/Asenapine n=227 Participants 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.	Placebo/Asenapine n=72 Participants 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.
Change From Baseline in PQ-LES-Q Overall Score Day 182 (n=111, 36)	0.1 Score on a scale Standard Deviation 0.8	0.3 Score on a scale Standard Deviation 0.8
Change From Baseline in PQ-LES-Q Overall Score Day 350 (n=45, 20)	0.4 Score on a scale Standard Deviation 1.0	0.3 Score on a scale Standard Deviation 0.9

Adverse Events

Asenapine/Asenapine

Serious events: 17 serious events

Other events: 135 other events

Deaths: 0 deaths

Placebo/Asenapine

Serious events: 6 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Measure	Asenapine/Asenapine n=241 participants at risk 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.	Placebo/Asenapine n=81 participants at risk 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.
Gastrointestinal disorders Swollen tongue	0.00% 0/241 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	1.2% 1/81 • Number of events 2 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Immune system disorders Drug hypersensitivity	0.00% 0/241 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	1.2% 1/81 • Number of events 2 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Injury, poisoning and procedural complications Accidental overdose	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Injury, poisoning and procedural complications Intentional overdose	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Nervous system disorders Dystonia	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Nervous system disorders Loss of consciousness	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Nervous system disorders Somnolence	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Aggression	0.83% 2/241 • Number of events 2 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	1.2% 1/81 • Number of events 2 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Agitation	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	1.2% 1/81 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Anxiety	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Bipolar disorder	0.83% 2/241 • Number of events 3 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	2.5% 2/81 • Number of events 2 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Depression	1.2% 3/241 • Number of events 3 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Disturbance in social behaviour	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Exhibitionism	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Impulsive behaviour	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Mania	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Self-injurious ideation	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Suicidal behaviour	0.41% 1/241 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	0.00% 0/81 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Psychiatric disorders Suicidal ideation	2.9% 7/241 • Number of events 8 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	1.2% 1/81 • Number of events 1 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants

Other adverse events

Measure	Asenapine/Asenapine n=241 participants at risk 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.	Placebo/Asenapine n=81 participants at risk 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.
Gastrointestinal disorders Abdominal pain upper	4.1% 10/241 • Number of events 15 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	7.4% 6/81 • Number of events 6 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Gastrointestinal disorders Hypoaesthesia oral	0.83% 2/241 • Number of events 2 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	13.6% 11/81 • Number of events 11 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Gastrointestinal disorders Nausea	6.2% 15/241 • Number of events 17 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	11.1% 9/81 • Number of events 9 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Gastrointestinal disorders Paraesthesia oral	1.2% 3/241 • Number of events 3 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	9.9% 8/81 • Number of events 10 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Gastrointestinal disorders Vomiting	6.6% 16/241 • Number of events 18 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	4.9% 4/81 • Number of events 4 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
General disorders Fatigue	6.2% 15/241 • Number of events 17 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	7.4% 6/81 • Number of events 7 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Infections and infestations Gastroenteritis viral	1.7% 4/241 • Number of events 4 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	6.2% 5/81 • Number of events 5 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Investigations Weight increased	17.4% 42/241 • Number of events 43 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	19.8% 16/81 • Number of events 16 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Metabolism and nutrition disorders Increased appetite	6.6% 16/241 • Number of events 18 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	7.4% 6/81 • Number of events 6 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Nervous system disorders Dizziness	2.1% 5/241 • Number of events 6 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	9.9% 8/81 • Number of events 10 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Nervous system disorders Dysgeusia	1.7% 4/241 • Number of events 4 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	6.2% 5/81 • Number of events 5 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Nervous system disorders Headache	8.7% 21/241 • Number of events 30 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	13.6% 11/81 • Number of events 21 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Nervous system disorders Sedation	9.5% 23/241 • Number of events 29 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	23.5% 19/81 • Number of events 27 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants
Nervous system disorders Somnolence	18.3% 44/241 • Number of events 50 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants	35.8% 29/81 • Number of events 36 • 30 days after the last dose of study drug (up to approximately 54 weeks). All enrolled and treated participants

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER