Trial Outcomes & Findings for Fixed Dose Efficacy and Safety Study of Asenapine for the Treatment of Schizophrenia in Adolescents (P05896) (NCT NCT01190254)

NCT ID: NCT01190254

Last Updated: 2024-05-21

Results Overview

The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 306 participants
• Primary outcome timeframe: Baseline and Day 56
• Results posted on: 2024-05-21

Participant Flow

Participant milestones

Measure	Placebo Participants receive placebo asenapine tablets sublingually twice daily (BID) for 8 weeks	Asenapine 2.5 mg BID Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Overall Study STARTED	102	98	106
Overall Study Treated	102	98	106
Overall Study COMPLETED	81	81	84
Overall Study NOT COMPLETED	21	17	22

Reasons for withdrawal

Measure	Placebo Participants receive placebo asenapine tablets sublingually twice daily (BID) for 8 weeks	Asenapine 2.5 mg BID Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Overall Study Adverse Event	3	6	8
Overall Study Lack of Efficacy	7	4	5
Overall Study Lost to Follow-up	4	2	0
Overall Study Withdrawal by Subject	4	5	7
Overall Study Protocol Violation	2	0	2
Overall Study Did not meet protocol eligibility	1	0	0

Baseline Characteristics

Fixed Dose Efficacy and Safety Study of Asenapine for the Treatment of Schizophrenia in Adolescents (P05896)

Baseline characteristics by cohort

Measure	Placebo n=102 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=98 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=106 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period	Total n=306 Participants Total of all reporting groups
Age, Continuous	15.4 years STANDARD_DEVIATION 1.4 • n=5 Participants	15.2 years STANDARD_DEVIATION 1.5 • n=7 Participants	15.4 years STANDARD_DEVIATION 1.5 • n=5 Participants	15.3 years STANDARD_DEVIATION 1.5 • n=4 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	36 Participants n=7 Participants	39 Participants n=5 Participants	115 Participants n=4 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	62 Participants n=7 Participants	67 Participants n=5 Participants	191 Participants n=4 Participants
Positive and Negative Syndrome Scale (PANSS) total score	97.5 score on a scale STANDARD_DEVIATION 10.3 • n=5 Participants	97.4 score on a scale STANDARD_DEVIATION 10.2 • n=7 Participants	98.6 score on a scale STANDARD_DEVIATION 13.4 • n=5 Participants	97.9 score on a scale STANDARD_DEVIATION 11.4 • n=4 Participants
Clinical Global Impression of Severity (CGI-S) score	4.6 score on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	4.6 score on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	4.7 score on a scale STANDARD_DEVIATION 0.6 • n=5 Participants	4.6 score on a scale STANDARD_DEVIATION 0.6 • n=4 Participants
PANSS positive subscale score	25.5 score on a scale STANDARD_DEVIATION 3.8 • n=5 Participants	25.4 score on a scale STANDARD_DEVIATION 4.2 • n=7 Participants	26.2 score on a scale STANDARD_DEVIATION 4.5 • n=5 Participants	25.7 score on a scale STANDARD_DEVIATION 4.2 • n=4 Participants
PANSS negative subscale score	25.0 score on a scale STANDARD_DEVIATION 4.5 • n=5 Participants	24.9 score on a scale STANDARD_DEVIATION 4.8 • n=7 Participants	24.5 score on a scale STANDARD_DEVIATION 5.4 • n=5 Participants	24.8 score on a scale STANDARD_DEVIATION 4.9 • n=4 Participants
PANSS positive and negative subscale scores combined	50.5 score on a scale STANDARD_DEVIATION 5.7 • n=5 Participants	50.2 score on a scale STANDARD_DEVIATION 5.9 • n=7 Participants	50.7 score on a scale STANDARD_DEVIATION 7.3 • n=5 Participants	50.5 score on a scale STANDARD_DEVIATION 6.3 • n=4 Participants
PANSS general psychopathology subscale score	47.1 score on a scale STANDARD_DEVIATION 6.4 • n=5 Participants	47.2 score on a scale STANDARD_DEVIATION 6.0 • n=7 Participants	47.9 score on a scale STANDARD_DEVIATION 7.7 • n=5 Participants	47.4 score on a scale STANDARD_DEVIATION 6.8 • n=4 Participants
PANSS Marder positive symptoms factor score	28.4 score on a scale STANDARD_DEVIATION 4.0 • n=5 Participants	28.7 score on a scale STANDARD_DEVIATION 3.6 • n=7 Participants	28.9 score on a scale STANDARD_DEVIATION 4.3 • n=5 Participants	28.7 score on a scale STANDARD_DEVIATION 4.0 • n=4 Participants
PANSS Marder negative symptoms factor score	24.2 score on a scale STANDARD_DEVIATION 4.8 • n=5 Participants	23.9 score on a scale STANDARD_DEVIATION 5.4 • n=7 Participants	23.8 score on a scale STANDARD_DEVIATION 5.9 • n=5 Participants	23.9 score on a scale STANDARD_DEVIATION 5.4 • n=4 Participants
PANSS Marder disorganized thoughts factor score	22.4 score on a scale STANDARD_DEVIATION 3.7 • n=5 Participants	22.3 score on a scale STANDARD_DEVIATION 3.4 • n=7 Participants	22.5 score on a scale STANDARD_DEVIATION 4.6 • n=5 Participants	22.4 score on a scale STANDARD_DEVIATION 3.9 • n=4 Participants
PANSS Marder hostility/excitement factor score	12.9 score on a scale STANDARD_DEVIATION 3.5 • n=5 Participants	12.8 score on a scale STANDARD_DEVIATION 3.6 • n=7 Participants	13.1 score on a scale STANDARD_DEVIATION 4.3 • n=5 Participants	12.9 score on a scale STANDARD_DEVIATION 3.8 • n=4 Participants
PANSS Marder anxiety/depression factor score	9.6 score on a scale STANDARD_DEVIATION 3.1 • n=5 Participants	9.8 score on a scale STANDARD_DEVIATION 3.1 • n=7 Participants	10.3 score on a scale STANDARD_DEVIATION 3.1 • n=5 Participants	9.9 score on a scale STANDARD_DEVIATION 3.1 • n=4 Participants
Children's Global Assessment Scale (CGAS) score - current functioning	43.0 score on a scale STANDARD_DEVIATION 8.4 • n=5 Participants	41.6 score on a scale STANDARD_DEVIATION 9.1 • n=7 Participants	42.9 score on a scale STANDARD_DEVIATION 8.5 • n=5 Participants	42.5 score on a scale STANDARD_DEVIATION 8.7 • n=4 Participants
Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total score	41.6 score on a scale STANDARD_DEVIATION 10.7 • n=5 Participants	41.2 score on a scale STANDARD_DEVIATION 10.0 • n=7 Participants	40.7 score on a scale STANDARD_DEVIATION 9.5 • n=5 Participants	41.1 score on a scale STANDARD_DEVIATION 10.1 • n=4 Participants
PQ-LES-Q overall score	3.1 score on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	3.1 score on a scale STANDARD_DEVIATION 0.9 • n=7 Participants	3.0 score on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	3.1 score on a scale STANDARD_DEVIATION 1.0 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy Full Analysis Set \[FAS\]); also, to be included an on-treatment Day 56 value of PANSS Total Score must be available for a participant.

The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 56	-17.8 score on a scale Standard Deviation 17.8 • Interval -20.7 to -13.5	-23.7 score on a scale Standard Deviation 18.6 • Interval -25.5 to -18.2	-25.5 score on a scale Standard Deviation 16.9 • Interval -26.3 to -19.1

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the CGI-S score must be available for a participant.

Change from baseline in CGI-S score at Day 56 is the Key Secondary Outcome Measure. CGI-S is a 7-point scale for assessing the global severity of the participant's illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=76 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at Day 56	-0.8 score on a scale Standard Deviation 1.1 • Interval -1.0 to -0.6	-1.1 score on a scale Standard Deviation 1.0 • Interval -1.2 to -0.8	-1.3 score on a scale Standard Deviation 1.0 • Interval -1.4 to -1.0

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS positive subscale score must be available for a participant.

This measure reports results for the 7 items of the positive subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive subscale score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS Positive Subscale Score at Day 56	-6.0 score on a scale Standard Deviation 6.1 • Interval -7.1 to -4.7	-7.9 score on a scale Standard Deviation 5.8 • Interval -8.7 to -6.3	-9.1 score on a scale Standard Deviation 5.6 • Interval -9.3 to -6.9

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS negative subscale score must be available for a participant.

This measure reports results for the 7 items of the negative subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS negative subscale score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS Negative Subscale Score at Day 56	-3.4 score on a scale Standard Deviation 5.2 • Interval -4.3 to -2.3	-4.8 score on a scale Standard Deviation 5.6 • Interval -5.5 to -3.5	-4.9 score on a scale Standard Deviation 4.5 • Interval -5.5 to -3.5

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS positive/negative subscale scores combined must be available for a participant.

This measure reports results for the combined positive subscale (7 items) and negative subscale (7 items) of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each of the total 14 items in the combined positive and negative subscales, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive and negative subscale scores combined for each participant was calculated as the sum of the rating assigned to each of the 14 combined subscale items, and ranged from 14 to 98 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS Positive and Negative Subscale Scores Combined at Day 56	-9.4 score on a scale Standard Deviation 10.1 • Interval -11.2 to -7.2	-12.7 score on a scale Standard Deviation 10.2 • Interval -14.0 to -9.9	-14.0 score on a scale Standard Deviation 8.8 • Interval -14.4 to -10.5

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS general psychopathology subscale score must be available for a participant.

This measure reports results for the 16 items of the general psychopathology subscale of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS general psychopathology subscale score for each participant was calculated as the sum of the rating assigned to each of the 16 subscale items, and ranged from 16 to 112 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS General Psychopathology Subscale Score at Day 56	-8.5 score on a scale Standard Deviation 8.6 • Interval -9.7 to -6.2	-10.9 score on a scale Standard Deviation 9.5 • Interval -11.9 to -8.3	-11.5 score on a scale Standard Deviation 8.9 • Interval -12.0 to -8.5

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder positive symptoms factor score must be available for a participant.

This measure reports results for the 8 items of the Marder positive symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items (Marder et al. J Clin Psychiatry 1997;58(12):538-46). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder positive symptoms factor score for each participant was calculated as the sum of the rating assigned to each of the 8 applicable Marder factor items, and ranged from 8 to 56 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS Marder Positive Symptoms Factor Score at Day 56	-6.1 score on a scale Standard Deviation 6.1 • Interval -7.3 to -4.9	-7.9 score on a scale Standard Deviation 6.1 • Interval -8.7 to -6.2	-8.9 score on a scale Standard Deviation 5.5 • Interval -9.2 to -6.8

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder negative symptoms factor score must be available for a participant.

This measure reports results for the 7 items of the Marder negative symptoms factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder negative symptoms factor score for each participant was calculated as the sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS Marder Negative Symptoms Factor Score at Day 56	-3.7 score on a scale Standard Deviation 5.3 • Interval -4.6 to -2.6	-5.2 score on a scale Standard Deviation 5.5 • Interval -5.9 to -3.9	-5.3 score on a scale Standard Deviation 4.5 • Interval -5.9 to -3.9

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder disorganized thoughts factor score must be available for a participant.

This measure reports results for the 7 items of the Marder disorganized thoughts factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder disorganized thoughts factor score for each participant was calculated as the sum of the rating assigned to each of the 7 applicable Marder factor items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS Marder Disorganized Thoughts Factor Score at Day 56	-3.4 score on a scale Standard Deviation 4.1 • Interval -4.3 to -2.6	-4.3 score on a scale Standard Deviation 4.3 • Interval -5.2 to -3.5	-4.8 score on a scale Standard Deviation 4.3 • Interval -5.2 to -3.5

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder hostility/excitement factor score must be available for a participant.

This measure reports results for the 4 items of the Marder hostility/excitement factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder hostility/excitement factor score for each participant was calculated as the sum of the rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS Marder Hostility/Excitement Factor Score at Day 56	-2.8 score on a scale Standard Deviation 4.0 • Interval -3.3 to -1.8	-3.8 score on a scale Standard Deviation 3.6 • Interval -4.3 to -2.8	-3.8 score on a scale Standard Deviation 4.3 • Interval -4.1 to -2.6

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the PANSS Marder anxiety/depression factor score must be available for a participant.

This measure reports results for the 4 items of the Marder anxiety/depression factor of the PANSS, which is a 30-item clinician-rated instrument used to assess the symptoms of schizophrenia. Marder factors are a modified grouping of the 30 PANSS items. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder anxiety/depression factor score for each participant was calculated as the sum of the rating assigned to each of the 4 applicable Marder factor items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Day 56; improvement in symptoms is represented by negative values.

Outcome measures

Measure	Placebo n=77 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PANSS Marder Anxiety/Depression Factor Score at Day 56	-1.8 score on a scale Standard Deviation 2.4 • Interval -2.3 to -1.2	-2.4 score on a scale Standard Deviation 2.9 • Interval -2.7 to -1.6	-2.7 score on a scale Standard Deviation 2.9 • Interval -2.8 to -1.8

SECONDARY outcome

Timeframe: Baseline up to Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS).

A Total PANSS 30% responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS Total score at the last available assessment of the study for that participant (i.e., endpoint). The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms.

Outcome measures

Measure	Placebo n=100 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=96 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=104 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Total PANSS 30% Responders	36 participants	48 participants	51 participants

SECONDARY outcome

Timeframe: Baseline up to approximately Day 59

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS).

A total PANSS 30% response was defined as a reduction from baseline of at least 30% in the PANSS Total score. The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The Total score is the sum of the ratings for the individual items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The Kaplan-Meier estimate reports the cumulative percentage of participants with total PANSS 30% response from first drug intake up to approximately Day 59.

Outcome measures

Measure	Placebo n=100 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=96 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=104 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Kaplan-Meier Estimate of Cumulative Percentage of Participants With Total PANSS 30% Response at End of Study	62.0 cumulative % of participants w/ Response	64.2 cumulative % of participants w/ Response	72.1 cumulative % of participants w/ Response

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included an on-treatment Day 56 value of the CGI-I score must be available for a participant.

CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse.

Outcome measures

Measure	Placebo n=76 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Clinical Global Impression of Improvement (CGI-I) Score at Day 56	3.1 score on a scale Standard Deviation 1.1 • Interval 2.9 to 3.4	2.8 score on a scale Standard Deviation 1.1 • Interval 2.7 to 3.1	2.5 score on a scale Standard Deviation 1.0 • Interval 2.5 to 2.9

SECONDARY outcome

Timeframe: Baseline up to Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS).

A CGI-I responder was defined as a participant who had a CGI-I score of 1 (very much improved) or 2 (much improved) at the last available assessment of the study for that participant (i.e., endpoint). CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse.

Outcome measures

Measure	Placebo n=100 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=96 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=104 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
CGI-I Responders	28 participants Interval -7.1 to -4.7	36 participants Interval -8.7 to -6.3	41 participants Interval -9.3 to -6.9

SECONDARY outcome

Timeframe: Baseline up to approximately Day 58

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS).

CGI-I response was defined as the occurrence of a CGI-I score of 1 (very much improved) or 2 (much improved). CGI-I is a 7-point scale for assessing the global improvement of the participant's illness relative to baseline, with ratings from 1=very much improved to 7=very much worse. The Kaplan-Meier estimate reports the cumulative percentage of participants with CGI-I response from first drug intake up to approximately Day 58.

Outcome measures

Measure	Placebo n=100 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=96 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=104 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Kaplan-Meier Estimate of Cumulative Percentage of Participants With CGI-I Response at End of Study	54.7 cumulative % of participants w/ Response	47.1 cumulative % of participants w/ Response	60.1 cumulative % of participants w/ Response

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 56 value of the CGAS score must be available for a participant.

CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The reported measure is the change from baseline at Day 56; improvement in functioning is represented by positive values.

Outcome measures

Measure	Placebo n=76 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=72 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=79 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 56	10.2 score on a scale Standard Deviation 12.9 • Interval 7.5 to 12.3	12.8 score on a scale Standard Deviation 12.1 • Interval 8.9 to 13.7	15.0 score on a scale Standard Deviation 10.8 • Interval 11.6 to 16.4

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of the PQ-LES-Q total score must be available for a participant.

PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant was calculated as the sum of the rating assigned to each of the first 14 items, and ranged from 14 to 70 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 56; improvement in quality of life is represented by positive values. This analysis used a last-observation-carried-forward (LOCF) approach; if no Day 56 value was available for a participant, the last available assessment prior to the Day 56 assessment was used.

Outcome measures

Measure	Placebo n=85 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=83 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=82 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 56	3.1 score on a scale Standard Deviation 8.9 • Interval 1.8 to 4.9	3.9 score on a scale Standard Deviation 9.3 • Interval 2.4 to 5.5	6.1 score on a scale Standard Deviation 8.7 • Interval 3.9 to 7.0

SECONDARY outcome

Timeframe: Baseline and Day 56

Population: Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment PANSS Total Score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of the PQ-LES-Q overall score score must be available for a participant.

PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The Item 15 result is defined to be the PQ-LES-Q overall score, and ranged from 1 to 5 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 56; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 56 value was available for a participant, the last available assessment prior to the Day 56 assessment was used.

Outcome measures

Measure	Placebo n=85 Participants Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=83 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=82 Participants Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 56	0.2 score on a scale Standard Deviation 1.0 • Interval 0.1 to 0.4	0.3 score on a scale Standard Deviation 1.1 • Interval 0.2 to 0.5	0.5 score on a scale Standard Deviation 0.9 • Interval 0.2 to 0.6

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Asenapine 2.5 mg BID

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Asenapine 5.0 mg BID

Serious events: 3 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=102 participants at risk Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=98 participants at risk Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=106 participants at risk Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Psychiatric disorders Schizophrenia	2.9% 3/102 • Number of events 3 • Up to 30 days after the last dose of study drug	1.0% 1/98 • Number of events 1 • Up to 30 days after the last dose of study drug	1.9% 2/106 • Number of events 2 • Up to 30 days after the last dose of study drug
Psychiatric disorders Hallucination, auditory	0.00% 0/102 • Up to 30 days after the last dose of study drug	1.0% 1/98 • Number of events 1 • Up to 30 days after the last dose of study drug	0.00% 0/106 • Up to 30 days after the last dose of study drug
Infections and infestations Pneumonia	0.00% 0/102 • Up to 30 days after the last dose of study drug	1.0% 1/98 • Number of events 1 • Up to 30 days after the last dose of study drug	0.00% 0/106 • Up to 30 days after the last dose of study drug
Infections and infestations Typhoid fever	0.00% 0/102 • Up to 30 days after the last dose of study drug	0.00% 0/98 • Up to 30 days after the last dose of study drug	0.94% 1/106 • Number of events 1 • Up to 30 days after the last dose of study drug

Other adverse events

Measure	Placebo n=102 participants at risk Participants receive placebo asenapine tablets sublingually BID for 8 weeks	Asenapine 2.5 mg BID n=98 participants at risk Participants receive active asenapine 2.5 mg tablets sublingually BID for 8 weeks	Asenapine 5.0 mg BID n=106 participants at risk Participants receive active asenapine 2.5 mg tablets sublingually BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive active asenapine 5.0 mg tablets sublingually BID for the remainder of the 8-week treatment period
Nervous system disorders Somnolence	6.9% 7/102 • Number of events 7 • Up to 30 days after the last dose of study drug	20.4% 20/98 • Number of events 22 • Up to 30 days after the last dose of study drug	17.0% 18/106 • Number of events 21 • Up to 30 days after the last dose of study drug
Nervous system disorders Headache	5.9% 6/102 • Number of events 7 • Up to 30 days after the last dose of study drug	7.1% 7/98 • Number of events 12 • Up to 30 days after the last dose of study drug	7.5% 8/106 • Number of events 11 • Up to 30 days after the last dose of study drug
Nervous system disorders Sedation	2.0% 2/102 • Number of events 2 • Up to 30 days after the last dose of study drug	4.1% 4/98 • Number of events 4 • Up to 30 days after the last dose of study drug	11.3% 12/106 • Number of events 14 • Up to 30 days after the last dose of study drug
Nervous system disorders Akathisia	0.98% 1/102 • Number of events 1 • Up to 30 days after the last dose of study drug	4.1% 4/98 • Number of events 5 • Up to 30 days after the last dose of study drug	6.6% 7/106 • Number of events 9 • Up to 30 days after the last dose of study drug
Nervous system disorders Dizziness	0.98% 1/102 • Number of events 1 • Up to 30 days after the last dose of study drug	7.1% 7/98 • Number of events 7 • Up to 30 days after the last dose of study drug	1.9% 2/106 • Number of events 5 • Up to 30 days after the last dose of study drug
Psychiatric disorders Insomnia	5.9% 6/102 • Number of events 8 • Up to 30 days after the last dose of study drug	5.1% 5/98 • Number of events 6 • Up to 30 days after the last dose of study drug	9.4% 10/106 • Number of events 12 • Up to 30 days after the last dose of study drug
Gastrointestinal disorders Nausea	7.8% 8/102 • Number of events 9 • Up to 30 days after the last dose of study drug	2.0% 2/98 • Number of events 2 • Up to 30 days after the last dose of study drug	1.9% 2/106 • Number of events 2 • Up to 30 days after the last dose of study drug
Gastrointestinal disorders Hypoaesthesia oral	0.98% 1/102 • Number of events 1 • Up to 30 days after the last dose of study drug	5.1% 5/98 • Number of events 6 • Up to 30 days after the last dose of study drug	4.7% 5/106 • Number of events 5 • Up to 30 days after the last dose of study drug

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 It is planned to first publish/present trial results together with the other sites, unless permission is obtained from Sponsor to publish separate results. Sponsor must be able to review all proposed results communications regarding study 45 days prior to submission for publication/presentation. If there is disagreement concerning appropriateness of the materials, Investigator and Sponsor must meet to make a good faith effort to discuss/resolve disagreement prior to submission for publication.
• Publication restrictions are in place

Restriction type: OTHER