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Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Olanzapine as an Active Control in Subjects With an Acute Exacerbation of Schizophrenia (Phase 3B, Protocol P05688 [formerly 041038]).

Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.

Summary
EudraCT number	2010-018407-28
Trial protocol	BG
Global end of trial date	09 Sep 2014

Results information
Results version number	v1(current)
This version publication date	26 Feb 2016
First version publication date	26 Feb 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

P05688

ISRCTN number

US NCT number

NCT01617187

WHO universal trial number (UTN)

Other trial identifiers

Merck Protocol number: MK-8274-001

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

09 Sep 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Sep 2014

Was the trial ended prematurely?

Main objective of the trial

The purpose of this trial is to assess effect of asenapine 2.5 and 5 mg sublingually twice daily (BID) compared with placebo in treatment of schizophrenia (overall symptoms) as measured by the Positive and Negative Syndrome Scale (PANSS). Olanzapine administered 15 mg orally once daily (QD) was used as an active control. Primary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by change from Baseline in PANSS total score at Day 42. The first key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by change from Baseline in Clinical Global Impression Scale-Severity (CGI-S) score at Day 42. The second key secondary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by rate of PANSS responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Dec 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

8 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 53

Country: Number of subjects enrolled

Romania: 37

Country: Number of subjects enrolled

Russian Federation: 73

Country: Number of subjects enrolled

Ukraine: 38

Country: Number of subjects enrolled

United States: 140

Country: Number of subjects enrolled

Croatia: 19

Worldwide total number of subjects

360

EEA total number of subjects

109

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

357

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

One participant randomized to asenapine 2.5 mg BID did not receive study drug but was recorded in clinical database as completing the study. In Subject Disposition table, this participant is presented as Not Completed in period "Randomization through Start Treatment" (Not Treated).

Period 1 title

Randomization through Start Treatment

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Asenapine 2.5 mg BID

Arm description

Participants were administered one 2.5 mg asenapine tablet BID for 42 days

Arm type

Experimental

Investigational medicinal product name

Asenapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Sublingual tablet

Routes of administration

Sublingual use

Dosage and administration details

2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually

Investigational medicinal product name

Placebo Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

Asenapine 5 mg BID

Arm description

Participants were administered one 5 mg asenapine tablet BID for 42 days

Arm type

Experimental

Investigational medicinal product name

Asenapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Sublingual tablet

Routes of administration

Sublingual use

Dosage and administration details

2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually

Investigational medicinal product name

Placebo Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

Olanzapine 15 mg QD

Arm description

Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

Arm type

Active comparator

Investigational medicinal product name

Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

5 and 10 mg film-coated active olanzapine tablets administered orally QD. The time of the active olanzapine dose (either morning or evening) is not disclosed in order to preserve blinding

Investigational medicinal product name

Placebo Asenapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Sublingual tablet

Routes of administration

Sublingual use

Dosage and administration details

Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually

Investigational medicinal product name

Placebo Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

Placebo BID

Arm description

Participants were administered placebo tablets BID for 42 days

Arm type

Placebo

Investigational medicinal product name

Placebo Asenapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Sublingual tablet

Routes of administration

Sublingual use

Dosage and administration details

Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually

Investigational medicinal product name

Placebo Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

Number of subjects in period 1	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Started	98	113	46	103
Completed	97	113	46	101
Not completed	1	0	0	2
Not Treated: Completed study in database	1	-	-	-
Not Treated: Administrative Reason	-	-	-	1
Not Treated: Adverse Event	-	-	-	1

Period 2 title

Treatment through Study Completion

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Asenapine 2.5 mg BID

Arm description

Participants were administered one 2.5 mg asenapine tablet BID for 42 days

Arm type

Experimental

Investigational medicinal product name

Asenapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Sublingual tablet

Routes of administration

Sublingual use

Dosage and administration details

2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually

Investigational medicinal product name

Placebo Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

Asenapine 5 mg BID

Arm description

Participants were administered one 5 mg asenapine tablet BID for 42 days

Arm type

Experimental

Investigational medicinal product name

Asenapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Sublingual tablet

Routes of administration

Sublingual use

Dosage and administration details

2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually

Investigational medicinal product name

Placebo Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

Olanzapine 15 mg QD

Arm description

Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

Arm type

Active comparator

Investigational medicinal product name

Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

5 and 10 mg film-coated active olanzapine tablets administered orally QD. The time of the active olanzapine dose (either morning or evening) is not disclosed in order to preserve blinding

Investigational medicinal product name

Placebo Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

Investigational medicinal product name

Placebo Asenapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Sublingual tablet

Routes of administration

Sublingual use

Dosage and administration details

Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually

Placebo BID

Arm description

Participants were administered placebo tablets BID for 42 days

Arm type

Placebo

Investigational medicinal product name

Placebo Olanzapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally

Investigational medicinal product name

Placebo Asenapine

Investigational medicinal product code

Other name

Pharmaceutical forms

Sublingual tablet

Routes of administration

Sublingual use

Dosage and administration details

Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: The participants who started Period 1 are those randomized, 3 of whom did not receive study drug. The participants who started Period 2 are those who received study drug. The baseline demographics table presents data for participants treated, therefore Period 2 was set as the baseline period.

Number of subjects in period 2 ^[2]	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Started	97	113	46	101
Completed	86	102	41	91
Not completed	11	11	5	10
Consent withdrawn by subject	5	8	3	6
Adverse event, non-fatal	1	1	-	1
Lost to follow-up	4	2	2	2
Protocol deviation	1	-	-	1

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The worldwide number enrolled in the trial presents participants randomized; 3 of these participants did not receive study drug. The participants who started Period 2 ("baseline period") are those who received study drug. The baseline demographics table presents data for participants treated, therefore Period 2 was set as the baseline period.

Baseline characteristics

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Reporting group title

Asenapine 2.5 mg BID

Reporting group description

Participants were administered one 2.5 mg asenapine tablet BID for 42 days

Reporting group title

Asenapine 5 mg BID

Reporting group description

Participants were administered one 5 mg asenapine tablet BID for 42 days

Reporting group title

Olanzapine 15 mg QD

Reporting group description

Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

Reporting group title

Placebo BID

Reporting group description

Participants were administered placebo tablets BID for 42 days

Reporting group values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID	Total
Number of subjects	97	113	46	101	357
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	41.5 ± 10.79	39.1 ± 10.68	40.8 ± 11.15	41.4 ± 12.05	-
Gender categorical
Units: Subjects
Female	39	44	18	47	148
Male	58	69	28	54	209
Positive and Negative Syndrome Scale (PANSS) total score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score (30 items) ranged from 30 to 210 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	93.3 ± 11.1	95.8 ± 13.77	92.7 ± 10.47	93.4 ± 11.16	-
Clinical Global Impression Scale-Severity (CGI-S) score
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. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	4.8 ± 0.64	4.9 ± 0.64	4.8 ± 0.61	4.8 ± 0.61	-
Body Weight
Units: kg
arithmetic mean (standard deviation)	81.6 ± 17.73	78.6 ± 17.88	80.7 ± 17.79	77.1 ± 17.56	-
PANSS negative subscale score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS negative subscale score (7 PANSS items) ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	23.5 ± 4.47	24.1 ± 4.5	23.4 ± 3.96	23.9 ± 4.22	-
PANSS positive subscale score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS positive subscale score (7 PANSS items) ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	24.4 ± 4.05	25.5 ± 4.76	24.6 ± 3.46	24.6 ± 3.88	-
PANSS general psychopathology subscale score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS general psychopathology subscale score (16 PANSS items) ranged from 16 to 112 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	45.5 ± 6.05	46.3 ± 6.87	44.7 ± 6.2	44.9 ± 6.05	-
PANSS Marder factor positive symptom score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor positive symptom score (calculated from value of 8 identified PANSS items) ranged from 8 to 56 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	29.3 ± 5.02	30 ± 5.05	29 ± 4.69	29.4 ± 4.36	-
PANSS Marder factor negative symptom score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor negative symptom score (calculated from value of 7 identified PANSS items) ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	22.6 ± 4.3	23 ± 4.66	23 ± 4.44	22.8 ± 4.76	-
PANSS Marder factor disorganized thought symptom score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor disorganized thought symptom score (calculated from value of 7 identified PANSS items) ranged from 7 to 49 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	21.5 ± 4.32	22.6 ± 4.93	21.2 ± 4.29	21.6 ± 4.42	-
PANSS Marder factor hostility/excitement symptom score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor hostility/excitement symptom score (calculated from value of 4 identified PANSS items) ranged from 4 to 28 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	9 ± 2.99	9.4 ± 3.49	8.7 ± 3.11	8.8 ± 3.22	-
PANSS Marder factor anxiety/depression symptom score
The PANSS is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Marder factor anxiety/depression symptom score (calculated from value of 4 identified PANSS items) ranged from 4 to 28 with a higher score indicating greater severity of symptoms. Summary statistics presented are for efficacy population (FAS): N=96, 111, 45 and 99 for asenapine 2.5 mg BID, asenapine 5 mg BID, olanzapine 15 mg QD and placebo BID groups, respectively.
Units: score on a scale
arithmetic mean (standard deviation)	11 ± 2.97	10.9 ± 3.13	10.9 ± 3.62	10.7 ± 2.96	-

End points

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Reporting group title

Asenapine 2.5 mg BID

Reporting group description

Participants were administered one 2.5 mg asenapine tablet BID for 42 days

Reporting group title

Asenapine 5 mg BID

Reporting group description

Participants were administered one 5 mg asenapine tablet BID for 42 days

Reporting group title

Olanzapine 15 mg QD

Reporting group description

Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

Reporting group title

Placebo BID

Reporting group description

Participants were administered placebo tablets BID for 42 days

Reporting group title

Asenapine 2.5 mg BID

Reporting group description

Participants were administered one 2.5 mg asenapine tablet BID for 42 days

Reporting group title

Asenapine 5 mg BID

Reporting group description

Participants were administered one 5 mg asenapine tablet BID for 42 days

Reporting group title

Olanzapine 15 mg QD

Reporting group description

Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

Reporting group title

Placebo BID

Reporting group description

Participants were administered placebo tablets BID for 42 days

Primary: Change From Baseline in PANSS Total Score at Day 42

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End point title

Change From Baseline in PANSS Total Score at Day 42

End point description

The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). 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 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 42; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Primary

End point timeframe

Baseline and Day 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)	-17.4 ± 1.8	-21.7 ± 1.6	-21.6 ± 2.32	-16.2 ± 1.71

Comparison by Treatment Group

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, Mixed Model Repeated Measures (MMRM) model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6043 ^[1]

Method

MMRM

Parameter type

Least Squares (LS) means difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

3.6

Variability estimate

Standard error of the mean

Dispersion value

2.46

Notes
[1] - Adjusted p-value from graphical approach to control Type 1 error rate among primary and secondary efficacy hypotheses

Comparison by Treatment Group

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0356 ^[2]

Method

MMRM

Parameter type

LS means difference

Point estimate

-5.5

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

-1

Variability estimate

Standard error of the mean

Dispersion value

2.32

Notes
[2] - Adjusted p-value from graphical approach to control Type 1 error rate among primary and secondary efficacy hypotheses

Comparison by Treatment Group

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0587 ^[3]

Method

MMRM

Parameter type

LS means difference

Point estimate

-5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-11.1

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

2.86

Notes
[3] - Unadjusted p-value

Secondary: Change From Baseline in CGI-S Score at Day 42

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End point title

Change From Baseline in CGI-S Score at Day 42

End point description

Change from baseline in CGI-S score at Day 42 is a 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 42; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Day 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)	-0.9 ± 0.11	-1.2 ± 0.1	-1.1 ± 0.14	-1 ± 0.11

Comparison by Treatment Group

Statistical analysis description

“Number of subjects included in analysis” below is sum of participants in FAS population in the 2 treatment groups compared and is automatically calculated by data entry system; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants. Confirmative testing of asenapine versus placebo was performed only if both asenapine doses were statistically superior to placebo in reduction from baseline in PANSS Total Score at Day 42.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9083 ^[4]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.15

Notes
[4] - Unadjusted p-value

Comparison by Treatment Group

Statistical analysis description

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0601 ^[5]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[5] - Unadjusted p-value

Comparison by Treatment Group

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3898 ^[6]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.18

Notes
[6] - Unadjusted p-value

Secondary: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42

Top of page

End point title

Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42

End point description

Rate of PANSS responders at Day 42 is a Key Secondary Outcome Measure. A PANSS responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS total score at a post-baseline assessment. The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. 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. Missing data were imputed by Last Observation Carried Forward (LOCF). Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Day 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: percentage of participants
number (not applicable)	14.6	25.2	26.7	19.2

Comparison by Treatment Group

Statistical analysis description

Confirmative testing of asenapine versus placebo for this measure was to be performed only if both asenapine doses were statistically superior to placebo in reduction from baseline in PANSS Total Score at Day 42.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.37 ^[7]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[7] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group

Statistical analysis description

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1708 ^[8]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[8] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.262 ^[9]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[9] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Secondary: Change From Baseline in Body Weight at Day 42

Top of page

End point title

Change From Baseline in Body Weight at Day 42

End point description

Change from baseline in body weight at Day 42 is the Key Safety Outcome Measure. Population for this analysis was all randomized participants who received ≥1 dose of study drug.

End point type

Secondary

End point timeframe

Baseline and Day 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	97	113	46	101
Units: kg
least squares mean (standard error)	1.3 ± 0.38	1.3 ± 0.33	2.4 ± 0.47	0.3 ± 0.35

Comparison by Treatment Group

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the all subjects treated population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire all subjects treated population in all 4 treatment groups, which includes 357 participants.

Comparison groups

Asenapine 2.5 mg BID v Olanzapine 15 mg QD

Number of subjects included in analysis

143

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0491 ^[10]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.6

Notes
[10] - p-value adjusted for multiple comparisons using Hochberg's method

Comparison by Treatment Group

Statistical analysis description

Comparison groups

Asenapine 5 mg BID v Olanzapine 15 mg QD

Number of subjects included in analysis

159

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0491 ^[11]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.57

Notes
[11] - p-value adjusted for multiple comparisons using Hochberg's method

Comparison by Treatment Group

Statistical analysis description

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0567 ^[12]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[12] - Unadjusted p-value

Comparison by Treatment Group

Statistical analysis description

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

214

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0391 ^[13]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

1.9

Variability estimate

Standard error of the mean

Dispersion value

0.48

Notes
[13] - Unadjusted p-value

Comparison by Treatment Group

Statistical analysis description

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

147

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0003 ^[14]

Method

MMRM

Parameter type

LS means difference

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

3.3

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[14] - Unadjusted p-value

Secondary: Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35

Top of page

End point title

Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35

End point description

The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). 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 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; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28 and 35

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-4 ± 0.8	-4.9 ± 0.76	-5.5 ± 1.15	-4.8 ± 0.81
Day 7	-7.2 ± 1.17	-9.1 ± 1.09	-9.3 ± 1.67	-7.1 ± 1.16
Day 14	-9.9 ± 1.31	-12.5 ± 1.19	-12.4 ± 1.8	-10.7 ± 1.28
Day 21	-12 ± 1.55	-14.8 ± 1.4	-15.2 ± 2.09	-13.2 ± 1.5
Day 28	-12.3 ± 1.69	-17.1 ± 1.49	-17.3 ± 2.21	-15.5 ± 1.61
Day 35	-17 ± 1.66	-19 ± 1.48	-20.3 ± 2.19	-15.4 ± 1.58

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4849 ^[15]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

2.9

Variability estimate

Standard error of the mean

Dispersion value

1.09

Notes
[15] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8902 ^[16]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

1.9

Variability estimate

Standard error of the mean

Dispersion value

1.06

Notes
[16] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5826 ^[17]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

1.9

Variability estimate

Standard error of the mean

Dispersion value

1.36

Notes
[17] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9271 ^[18]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.61

Notes
[18] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1902 ^[19]

Method

MMRM

Parameter type

LS means difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.56

Notes
[19] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.271 ^[20]

Method

MMRM

Parameter type

LS means difference

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

1.7

Variability estimate

Standard error of the mean

Dispersion value

Notes
[20] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6773 ^[21]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

4.3

Variability estimate

Standard error of the mean

Dispersion value

1.79

Notes
[21] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2895 ^[22]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

1.6

Variability estimate

Standard error of the mean

Dispersion value

1.72

Notes
[22] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4261 ^[23]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

2.6

Variability estimate

Standard error of the mean

Dispersion value

2.18

Notes
[23] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5505 ^[24]

Method

MMRM

Parameter type

LS means difference

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

5.5

Variability estimate

Standard error of the mean

Dispersion value

2.13

Notes
[24] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4286 ^[25]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.6

upper limit

2.4

Variability estimate

Standard error of the mean

Dispersion value

2.03

Notes
[25] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4423 ^[26]

Method

MMRM

Parameter type

LS means difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-7

upper limit

3.1

Variability estimate

Standard error of the mean

Dispersion value

2.56

Notes
[26] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1691 ^[27]

Method

MMRM

Parameter type

LS means difference

Point estimate

3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

7.7

Variability estimate

Standard error of the mean

Dispersion value

2.3

Notes
[27] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4682 ^[28]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

2.7

Variability estimate

Standard error of the mean

Dispersion value

2.17

Notes
[28] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4961 ^[29]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-7.2

upper limit

3.5

Variability estimate

Standard error of the mean

Dispersion value

2.71

Notes
[29] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4697 ^[30]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

2.8

Variability estimate

Standard error of the mean

Dispersion value

2.26

Notes
[30] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0947 ^[31]

Method

MMRM

Parameter type

LS means difference

Point estimate

-3.6

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

2.14

Notes
[31] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0675 ^[32]

Method

MMRM

Parameter type

LS means difference

Point estimate

-4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-10.2

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

2.68

Notes
[32] - Unadjusted p-value

Secondary: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35

Top of page

End point title

Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35

End point description

A PANSS responder was defined as a participant who had a reduction from baseline of at least 30% in the PANSS total score at a post-baseline assessment. The PANSS is a 30-item clinician-rated instrument for assessing schizophrenia symptoms. 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. Missing data were imputed by LOCF. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Days 4, 7, 14, 21, 28 and 35

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: percentage of participants
number (not applicable)
Day 4 (n = 95,108,44,97)	0	0	0	2.1
Day 7 (n = 96,111,45,99)	2.1	5.4	0	5.1
Day 14 (n = 96,111,45,99)	5.2	5.4	4.4	7.1
Day 21 (n = 96,111,45,99)	8.3	14.4	11.1	13.1
Day 28 (n = 96,111,45,99)	10.4	16.2	15.6	14.1
Day 35 (n = 96,111,45,99)	15.6	21.6	15.6	17.2

Comparison by Treatment Group: Day 4

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1736 ^[33]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[33] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 4

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1736 ^[34]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[34] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 4

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.285 ^[35]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[35] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 7

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.329 ^[36]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[36] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 7

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6938 ^[37]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[37] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 7

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1105 ^[38]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[38] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 14

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6804 ^[39]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[39] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 14

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9704 ^[40]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[40] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 14

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6604 ^[41]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[41] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 21

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2447 ^[42]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[42] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 21

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4834 ^[43]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[43] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 21

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9189 ^[44]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[44] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 28

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.437 ^[45]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[45] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 28

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2894 ^[46]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[46] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 28

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6953 ^[47]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[47] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 35

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4892 ^[48]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[48] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 35

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1954 ^[49]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[49] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 35

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.799 ^[50]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[50] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Secondary: Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35

Top of page

End point title

Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35

End point description

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; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28 and 35

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-0.1 ± 0.05	-0.2 ± 0.05	-0.2 ± 0.07	-0.2 ± 0.05
Day 7	-0.3 ± 0.07	-0.3 ± 0.06	-0.3 ± 0.1	-0.3 ± 0.07
Day 14	-0.6 ± 0.08	-0.6 ± 0.07	-0.6 ± 0.11	-0.5 ± 0.08
Day 21	-0.6 ± 0.1	-0.8 ± 0.09	-0.8 ± 0.13	-0.7 ± 0.09
Day 28	-0.7 ± 0.11	-0.9 ± 0.09	-0.8 ± 0.14	-0.8 ± 0.1
Day 35	-0.9 ± 0.11	-1.1 ± 0.1	-1 ± 0.14	-0.8 ± 0.1

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4255 ^[51]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.07

Notes
[51] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9564 ^[52]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.06

Notes
[52] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6363 ^[53]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.08

Notes
[53] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8759 ^[54]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.1

Notes
[54] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9598 ^[55]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.09

Notes
[55] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9789 ^[56]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.12

Notes
[56] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4671 ^[57]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.11

Notes
[57] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6359 ^[58]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.11

Notes
[58] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5454 ^[59]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[59] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4188 ^[60]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[60] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5318 ^[61]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[61] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5683 ^[62]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.16

Notes
[62] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2972 ^[63]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[63] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.482 ^[64]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.13

Notes
[64] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9901 ^[65]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.17

Notes
[65] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6682 ^[66]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.15

Notes
[66] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1111 ^[67]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.14

Notes
[67] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.24 ^[68]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.17

Notes
[68] - Unadjusted p-value

Secondary: Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42

End point description

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 a post-baseline assessment. 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. Missing data were imputed by LOCF. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: percentage of participants
number (not applicable)
Day 4 (n = 95,108,44,98)	34.7	33.3	43.2	37.8
Day 7 (n = 96,111,45,99)	51	46.8	60	45.5
Day 14 (n = 96,111,45,99)	51	60.4	71.1	54.5
Day 21 (n = 96,111,45,99)	54.2	63.1	75.6	58.6
Day 28 (n = 96,111,45,99)	58.3	62.2	73.3	60.6
Day 35 (n = 96,111,45,99)	60.4	64	82.2	64.6
Day 42 (n = 96,111,45,99)	59.4	66.7	84.4	62.6

Comparison by Treatment Group: Day 4

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6205 ^[69]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[69] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 4

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4829 ^[70]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[70] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 4

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3945 ^[71]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[71] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 7

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4076 ^[72]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[72] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 7

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.969 ^[73]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[73] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 7

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.117 ^[74]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[74] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 14

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5088 ^[75]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[75] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 14

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3426 ^[76]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[76] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 14

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0762 ^[77]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[77] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 21

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5531 ^[78]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[78] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 21

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4875 ^[79]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[79] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 21

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0692 ^[80]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[80] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 28

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7482 ^[81]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[81] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 28

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8037 ^[82]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[82] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 28

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0859 ^[83]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[83] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 35

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.585 ^[84]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[84] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 35

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9698 ^[85]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[85] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 35

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0132 ^[86]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[86] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 42

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7129 ^[87]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[87] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 42

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5074 ^[88]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[88] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Comparison by Treatment Group: Day 42

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.004 ^[89]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[89] - P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center

Secondary: Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

End point description

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 schizophrenia symptoms. 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. PANSS negative subscale score for each participant was 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. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-0.7 ± 0.29	-0.5 ± 0.27	-0.9 ± 0.42	-0.8 ± 0.29
Day 7	-1.2 ± 0.33	-1.3 ± 0.31	-1.5 ± 0.47	-1.1 ± 0.33
Day 14	-1.6 ± 0.37	-2.3 ± 0.34	-1.7 ± 0.51	-1.8 ± 0.37
Day 21	-2.3 ± 0.41	-2.5 ± 0.37	-2 ± 0.56	-2.3 ± 0.4
Day 28	-2.5 ± 0.45	-3.1 ± 0.4	-2.6 ± 0.59	-3 ± 0.43
Day 35	-3.3 ± 0.48	-3.4 ± 0.43	-3.4 ± 0.63	-2.6 ± 0.46
Day 42	-3.3 ± 0.54	-4.3 ± 0.48	-3.8 ± 0.68	-3.2 ± 0.51

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8829 ^[90]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[90] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5488 ^[91]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.39

Notes
[91] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.783 ^[92]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[92] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.807 ^[93]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.45

Notes
[93] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.528 ^[94]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.44

Notes
[94] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4025 ^[95]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.57

Notes
[95] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6471 ^[96]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

1.2

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[96] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2504 ^[97]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[97] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9223 ^[98]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.62

Notes
[98] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8839 ^[99]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

1.2

Variability estimate

Standard error of the mean

Dispersion value

0.56

Notes
[99] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8077 ^[100]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.54

Notes
[100] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6216 ^[101]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

1.7

Variability estimate

Standard error of the mean

Dispersion value

0.68

Notes
[101] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4248 ^[102]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

1.7

Variability estimate

Standard error of the mean

Dispersion value

0.61

Notes
[102] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7667 ^[103]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[103] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6282 ^[104]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.8

Variability estimate

Standard error of the mean

Dispersion value

0.72

Notes
[104] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.315 ^[105]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.65

Notes
[105] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1908 ^[106]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.61

Notes
[106] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3128 ^[107]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.77

Notes
[107] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8812 ^[108]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.73

Notes
[108] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1143 ^[109]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.69

Notes
[109] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4418 ^[110]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.84

Notes
[110] - Unadjusted p-value

Secondary: Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

End point description

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 schizophrenia symptoms. 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. PANSS positive subscale score for each participant was 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. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-1.2 ± 0.29	-1.6 ± 0.28	-2.3 ± 0.42	-1.7 ± 0.3
Day 7	-2.3 ± 0.39	-2.8 ± 0.36	-3.6 ± 0.55	-2.6 ± 0.38
Day 14	-3.4 ± 0.45	-3.9 ± 0.4	-4.4 ± 0.61	-3.7 ± 0.43
Day 21	-4 ± 0.52	-5 ± 0.47	-5.7 ± 0.7	-4.5 ± 0.51
Day 28	-4.1 ± 0.59	-5.7 ± 0.52	-6.2 ± 0.77	-5 ± 0.56
Day 35	-5.2 ± 0.6	-6.3 ± 0.53	-6.8 ± 0.78	-5.5 ± 0.57
Day 42	-5.6 ± 0.65	-7.2 ± 0.57	-7.5 ± 0.83	-5.4 ± 0.61

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.216 ^[111]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[111] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9494 ^[112]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.39

Notes
[112] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1834 ^[113]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[113] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6347 ^[114]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.53

Notes
[114] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6917 ^[115]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[115] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1431 ^[116]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.66

Notes
[116] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6267 ^[117]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

1.5

Variability estimate

Standard error of the mean

Dispersion value

0.61

Notes
[117] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.726 ^[118]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[118] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3326 ^[119]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.74

Notes
[119] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4575 ^[120]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

1.9

Variability estimate

Standard error of the mean

Dispersion value

0.72

Notes
[120] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.493 ^[121]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.68

Notes
[121] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1886 ^[122]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.86

Notes
[122] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2643 ^[123]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

2.5

Variability estimate

Standard error of the mean

Dispersion value

0.8

Notes
[123] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3516 ^[124]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.76

Notes
[124] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2068 ^[125]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.94

Notes
[125] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7284 ^[126]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

1.9

Variability estimate

Standard error of the mean

Dispersion value

0.82

Notes
[126] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2698 ^[127]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.77

Notes
[127] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.151 ^[128]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.96

Notes
[128] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8039 ^[129]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

1.5

Variability estimate

Standard error of the mean

Dispersion value

0.88

Notes
[129] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0306 ^[130]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.83

Notes
[130] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0406 ^[131]

Method

MMRM

Parameter type

LS means difference

Point estimate

-2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

1.03

Notes
[131] - Unadjusted p-value

Secondary: Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

End point description

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; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-2.2 ± 0.49	-2.7 ± 0.46	-2.5 ± 0.7	-2.4 ± 0.49
Day 7	-3.8 ± 0.69	-4.9 ± 0.64	-4.4 ± 0.98	-3.6 ± 0.68
Day 14	-5.1 ± 0.73	-6.2 ± 0.66	-6.4 ± 1	-5.4 ± 0.71
Day 21	-5.9 ± 0.84	-7.4 ± 0.76	-7.7 ± 1.13	-6.7 ± 0.81
Day 28	-5.9 ± 0.93	-8.2 ± 0.82	-8.6 ± 1.21	-7.7 ± 0.88
Day 35	-8.8 ± 0.88	-9.2 ± 0.79	-10.2 ± 1.16	-7.6 ± 0.84
Day 42	-8.9 ± 0.97	-10.1 ± 0.86	-10.4 ± 1.23	-8 ± 0.92

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7819 ^[132]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.5

Variability estimate

Standard error of the mean

Dispersion value

0.66

Notes
[132] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.703 ^[133]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.65

Notes
[133] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.952 ^[134]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

1.6

Variability estimate

Standard error of the mean

Dispersion value

0.83

Notes
[134] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7907 ^[135]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

1.6

Variability estimate

Standard error of the mean

Dispersion value

0.95

Notes
[135] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1391 ^[136]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.91

Notes
[136] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4901 ^[137]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

1.5

Variability estimate

Standard error of the mean

Dispersion value

1.18

Notes
[137] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8079 ^[138]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

2.2

Variability estimate

Standard error of the mean

Dispersion value

Notes
[138] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3889 ^[139]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.95

Notes
[139] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3907 ^[140]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

1.21

Notes
[140] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5363 ^[141]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.15

Notes
[141] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5075 ^[142]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

1.4

Variability estimate

Standard error of the mean

Dispersion value

1.09

Notes
[142] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4526 ^[143]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

1.7

Variability estimate

Standard error of the mean

Dispersion value

1.38

Notes
[143] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1548 ^[144]

Method

MMRM

Parameter type

LS means difference

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

4.3

Variability estimate

Standard error of the mean

Dispersion value

1.26

Notes
[144] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6589 ^[145]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

1.8

Variability estimate

Standard error of the mean

Dispersion value

1.19

Notes
[145] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5171 ^[146]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

Variability estimate

Standard error of the mean

Dispersion value

1.48

Notes
[146] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3133 ^[147]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

1.2

Variability estimate

Standard error of the mean

Dispersion value

1.2

Notes
[147] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1723 ^[148]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

1.13

Notes
[148] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0663 ^[149]

Method

MMRM

Parameter type

LS means difference

Point estimate

-2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

1.42

Notes
[149] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5128 ^[150]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

1.7

Variability estimate

Standard error of the mean

Dispersion value

1.32

Notes
[150] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0842 ^[151]

Method

MMRM

Parameter type

LS means difference

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

1.24

Notes
[151] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1217 ^[152]

Method

MMRM

Parameter type

LS means difference

Point estimate

-2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

1.52

Notes
[152] - Unadjusted p-value

Secondary: Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

End point description

This measure reports results for the 8 items of the Marder positive symptom factor of the PANSS, which is a 30-item clinician-rated instrument used to assess schizophrenia symptoms. 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. PANSS Marder factor positive symptom score for each participant was sum of 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. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-1.3 ± 0.29	-1.8 ± 0.27	-2 ± 0.41	-2 ± 0.29
Day 7	-2.5 ± 0.41	-2.9 ± 0.38	-3.2 ± 0.58	-2.8 ± 0.4
Day 14	-3.9 ± 0.49	-4 ± 0.44	-4.4 ± 0.67	-4.1 ± 0.47
Day 21	-4.5 ± 0.55	-5.4 ± 0.5	-5.5 ± 0.74	-5.1 ± 0.54
Day 28	-4.8 ± 0.6	-6.3 ± 0.53	-6.6 ± 0.78	-5.6 ± 0.57
Day 35	-6.1 ± 0.64	-6.7 ± 0.57	-6.9 ± 0.84	-6.1 ± 0.61
Day 42	-6.8 ± 0.67	-7.6 ± 0.59	-7.8 ± 0.86	-6.2 ± 0.63

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0584 ^[153]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

1.5

Variability estimate

Standard error of the mean

Dispersion value

0.39

Notes
[153] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5197 ^[154]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.38

Notes
[154] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9693 ^[155]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[155] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6161 ^[156]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

1.4

Variability estimate

Standard error of the mean

Dispersion value

0.56

Notes
[156] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.788 ^[157]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.54

Notes
[157] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5526 ^[158]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.7

Notes
[158] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7647 ^[159]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.5

Variability estimate

Standard error of the mean

Dispersion value

0.67

Notes
[159] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.89 ^[160]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.64

Notes
[160] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7097 ^[161]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.81

Notes
[161] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4601 ^[162]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

2.1

Variability estimate

Standard error of the mean

Dispersion value

0.76

Notes
[162] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6288 ^[163]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.72

Notes
[163] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6099 ^[164]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

1.3

Variability estimate

Standard error of the mean

Dispersion value

0.91

Notes
[164] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.279 ^[165]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

2.5

Variability estimate

Standard error of the mean

Dispersion value

0.82

Notes
[165] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4253 ^[166]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.77

Notes
[166] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3014 ^[167]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.96

Notes
[167] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.972 ^[168]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

1.7

Variability estimate

Standard error of the mean

Dispersion value

0.87

Notes
[168] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4758 ^[169]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.82

Notes
[169] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4419 ^[170]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

1.2

Variability estimate

Standard error of the mean

Dispersion value

1.03

Notes
[170] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4762 ^[171]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.91

Notes
[171] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1046 ^[172]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.86

Notes
[172] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1411 ^[173]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

1.06

Notes
[173] - Unadjusted p-value

Secondary: Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

End point description

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 schizophrenia symptoms. 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. PANSS Marder factor negative symptom score for each participant was 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. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-1.2 ± 0.3	-0.8 ± 0.28	-0.8 ± 0.43	-0.7 ± 0.3
Day 7	-1.7 ± 0.37	-1.9 ± 0.34	-1.8 ± 0.53	-1.3 ± 0.37
Day 14	-2 ± 0.41	-2.8 ± 0.37	-2.2 ± 0.56	-2 ± 0.4
Day 21	-2.6 ± 0.44	-3.2 ± 0.4	-2.6 ± 0.6	-2.5 ± 0.43
Day 28	-2.9 ± 0.51	-3.8 ± 0.45	-3.2 ± 0.67	-3.5 ± 0.49
Day 35	-3.5 ± 0.52	-3.9 ± 0.46	-4.1 ± 0.68	-3 ± 0.49
Day 42	-3.4 ± 0.53	-4.7 ± 0.47	-4.3 ± 0.67	-4 ± 0.51

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2754 ^[174]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[174] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.85 ^[175]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.39

Notes
[175] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8439 ^[176]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[176] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4741 ^[177]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[177] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2158 ^[178]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[178] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.506 ^[179]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.63

Notes
[179] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9956 ^[180]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.56

Notes
[180] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1624 ^[181]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.53

Notes
[181] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7662 ^[182]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.68

Notes
[182] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8363 ^[183]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.61

Notes
[183] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2388 ^[184]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[184] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9435 ^[185]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

1.4

Variability estimate

Standard error of the mean

Dispersion value

0.73

Notes
[185] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4267 ^[186]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

1.9

Variability estimate

Standard error of the mean

Dispersion value

0.7

Notes
[186] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.681 ^[187]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.65

Notes
[187] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7673 ^[188]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.9

Variability estimate

Standard error of the mean

Dispersion value

0.82

Notes
[188] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.483 ^[189]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.7

Notes
[189] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2128 ^[190]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.66

Notes
[190] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1756 ^[191]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.83

Notes
[191] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4246 ^[192]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.72

Notes
[192] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2873 ^[193]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.68

Notes
[193] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7308 ^[194]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

1.4

Variability estimate

Standard error of the mean

Dispersion value

0.83

Notes
[194] - Unadjusted p-value

Secondary: Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

End point description

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 schizophrenia symptoms. 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. PANSS Marder factor disorganized thought symptom score for each participant was sum of 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. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-0.3 ± 0.24	-0.7 ± 0.22	-1.1 ± 0.34	-0.7 ± 0.24
Day 7	-1 ± 0.32	-1.4 ± 0.29	-1.6 ± 0.45	-0.7 ± 0.31
Day 14	-1.3 ± 0.36	-2 ± 0.33	-2.2 ± 0.49	-1.5 ± 0.35
Day 21	-2.3 ± 0.41	-2.5 ± 0.37	-2.7 ± 0.54	-2.1 ± 0.39
Day 28	-2.4 ± 0.42	-3.1 ± 0.37	-3.1 ± 0.54	-2.4 ± 0.4
Day 35	-3.5 ± 0.43	-3.5 ± 0.38	-4.3 ± 0.56	-2.4 ± 0.41
Day 42	-3.8 ± 0.45	-4.3 ± 0.4	-4.7 ± 0.58	-2.7 ± 0.43

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2116 ^[195]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.32

Notes
[195] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9039 ^[196]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.31

Notes
[196] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2959 ^[197]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[197] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5909 ^[198]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.44

Notes
[198] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1489 ^[199]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.42

Notes
[199] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1 ^[200]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.54

Notes
[200] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.783 ^[201]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[201] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2679 ^[202]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.47

Notes
[202] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2321 ^[203]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.6

Notes
[203] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7368 ^[204]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.56

Notes
[204] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4606 ^[205]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.53

Notes
[205] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3241 ^[206]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.66

Notes
[206] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.986 ^[207]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.57

Notes
[207] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.189 ^[208]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.53

Notes
[208] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.303 ^[209]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.67

Notes
[209] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.055 ^[210]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[210] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0415 ^[211]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.55

Notes
[211] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0058 ^[212]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

-0.6

Variability estimate

Standard error of the mean

Dispersion value

0.69

Notes
[212] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0691 ^[213]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.62

Notes
[213] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0063 ^[214]

Method

MMRM

Parameter type

LS means difference

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

-0.5

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[214] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0056 ^[215]

Method

MMRM

Parameter type

LS means difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

-0.6

Variability estimate

Standard error of the mean

Dispersion value

0.71

Notes
[215] - Unadjusted p-value

Secondary: Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

End point description

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 schizophrenia symptoms. 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. PANSS Marder factor hostility/excitement symptom score for each participant was sum of 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. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-0.4 ± 0.25	-0.3 ± 0.23	-0.7 ± 0.36	-0.5 ± 0.25
Day 7	-0.5 ± 0.28	-0.5 ± 0.26	-1 ± 0.4	-0.7 ± 0.28
Day 14	-0.9 ± 0.3	-0.8 ± 0.27	-1.2 ± 0.41	-0.9 ± 0.3
Day 21	-0.8 ± 0.33	-0.9 ± 0.3	-1.8 ± 0.44	-1 ± 0.32
Day 28	-0.5 ± 0.41	-0.8 ± 0.36	-1.6 ± 0.53	-1 ± 0.39
Day 35	-1.4 ± 0.37	-1.5 ± 0.32	-2 ± 0.47	-1.4 ± 0.35
Day 42	-1.1 ± 0.41	-1.8 ± 0.36	-1.9 ± 0.52	-1.1 ± 0.39

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7847 ^[216]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.34

Notes
[216] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5859 ^[217]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.33

Notes
[217] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6413 ^[218]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.43

Notes
[218] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7307 ^[219]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.38

Notes
[219] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7176 ^[220]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.37

Notes
[220] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.486 ^[221]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.48

Notes
[221] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9321 ^[222]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.41

Notes
[222] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7691 ^[223]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.39

Notes
[223] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5694 ^[224]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[224] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5583 ^[225]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

1.2

Variability estimate

Standard error of the mean

Dispersion value

0.45

Notes
[225] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7307 ^[226]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.43

Notes
[226] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1715 ^[227]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.54

Notes
[227] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4219 ^[228]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

1.5

Variability estimate

Standard error of the mean

Dispersion value

0.55

Notes
[228] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7437 ^[229]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

1.2

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[229] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.311 ^[230]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.65

Notes
[230] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9805 ^[231]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.5

Notes
[231] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8741 ^[232]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.47

Notes
[232] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3288 ^[233]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.6

Variability estimate

Standard error of the mean

Dispersion value

0.58

Notes
[233] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9336 ^[234]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.56

Notes
[234] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1722 ^[235]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[235] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1909 ^[236]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.64

Notes
[236] - Unadjusted p-value

Secondary: Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Top of page

End point title

Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

End point description

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 schizophrenia symptoms. 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. PANSS Marder factor anxiety/depression symptom score for each participant was sum of 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. Measure reports change from baseline; improvement in symptoms is represented by negative values. Population for this analysis was FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score.

End point type

Secondary

End point timeframe

Baseline and Days 4, 7, 14, 21, 28, 35 and 42

End point values	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Number of subjects analysed	96	111	45	99
Units: score on a scale
least squares mean (standard error)
Day 4	-0.9 ± 0.27	-1.2 ± 0.25	-1 ± 0.38	-0.9 ± 0.27
Day 7	-1.5 ± 0.3	-2.2 ± 0.28	-1.8 ± 0.43	-1.7 ± 0.3
Day 14	-1.9 ± 0.31	-2.9 ± 0.28	-2.5 ± 0.42	-2.5 ± 0.3
Day 21	-2.1 ± 0.32	-3 ± 0.29	-2.7 ± 0.42	-3.1 ± 0.31
Day 28	-1.9 ± 0.36	-3.2 ± 0.32	-2.8 ± 0.47	-3.4 ± 0.35
Day 35	-3 ± 0.34	-3.6 ± 0.3	-3.2 ± 0.44	-3.2 ± 0.32
Day 42	-2.9 ± 0.4	-3.4 ± 0.35	-3.1 ± 0.5	-3 ± 0.38

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9851 ^[237]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.7

Variability estimate

Standard error of the mean

Dispersion value

0.37

Notes
[237] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4912 ^[238]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.36

Notes
[238] - Unadjusted p-value

Comparison by Treatment Group: Day 4

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8559 ^[239]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.8

Variability estimate

Standard error of the mean

Dispersion value

0.46

Notes
[239] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5635 ^[240]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.41

Notes
[240] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2321 ^[241]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.3

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[241] - Unadjusted p-value

Comparison by Treatment Group: Day 7

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8867 ^[242]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[242] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1499 ^[243]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

1.4

Variability estimate

Standard error of the mean

Dispersion value

0.42

Notes
[243] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.286 ^[244]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.4

Notes
[244] - Unadjusted p-value

Comparison by Treatment Group: Day 14

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8978 ^[245]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[245] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0283 ^[246]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

1.8

Variability estimate

Standard error of the mean

Dispersion value

0.44

Notes
[246] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8667 ^[247]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.9

Variability estimate

Standard error of the mean

Dispersion value

0.41

Notes
[247] - Unadjusted p-value

Comparison by Treatment Group: Day 21

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5044 ^[248]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

1.4

Variability estimate

Standard error of the mean

Dispersion value

0.52

Notes
[248] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.004 ^[249]

Method

MMRM

Parameter type

LS means difference

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

2.4

Variability estimate

Standard error of the mean

Dispersion value

0.49

Notes
[249] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.633 ^[250]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.46

Notes
[250] - Unadjusted p-value

Comparison by Treatment Group: Day 28

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2981 ^[251]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

1.7

Variability estimate

Standard error of the mean

Dispersion value

0.57

Notes
[251] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6556 ^[252]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.45

Notes
[252] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2889 ^[253]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.4

Variability estimate

Standard error of the mean

Dispersion value

0.43

Notes
[253] - Unadjusted p-value

Comparison by Treatment Group: Day 35

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9399 ^[254]

Method

MMRM

Parameter type

LS means difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.53

Notes
[254] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 2.5 mg BID v Placebo BID

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8955 ^[255]

Method

MMRM

Parameter type

LS means difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.54

Notes
[255] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Asenapine 5 mg BID v Placebo BID

Number of subjects included in analysis

210

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3681 ^[256]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.51

Notes
[256] - Unadjusted p-value

Comparison by Treatment Group: Day 42

Statistical analysis description

“Number of subjects included in analysis” presented below is sum of participants in the FAS population in the 2 treatment groups compared and is automatically calculated by data entry system for this record; however, MMRM model used for analysis includes entire FAS population in all 4 treatment groups, which includes 351 participants.

Comparison groups

Olanzapine 15 mg QD v Placebo BID

Number of subjects included in analysis

144

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8215 ^[257]

Method

MMRM

Parameter type

LS means difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.1

Variability estimate

Standard error of the mean

Dispersion value

0.62

Notes
[257] - Unadjusted p-value

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 30 days after last dose of study drug (Up to approximately 10 weeks)

Adverse event reporting additional description

Analysis population is all randomized participants who received ≥1 dose of study drug

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

Asenapine 2.5 mg BID

Reporting group description

Participants were administered one 2.5 mg asenapine tablet BID for 42 days

Reporting group title

Asenapine 5 mg BID

Reporting group description

Participants were administered one 5 mg asenapine tablet BID for 42 days

Reporting group title

Olanzapine 15 mg QD

Reporting group description

Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) QD for 42 days, except during Week 1 olanzapine 10 mg QD was administered

Reporting group title

Placebo BID

Reporting group description

Participants were administered placebo tablets BID for 42 days

Serious adverse events	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 97 (5.15%)	5 / 113 (4.42%)	1 / 46 (2.17%)	8 / 101 (7.92%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Injury, poisoning and procedural complications
Road traffic accident
subjects affected / exposed	0 / 97 (0.00%)	0 / 113 (0.00%)	0 / 46 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Epilepsy
subjects affected / exposed	0 / 97 (0.00%)	0 / 113 (0.00%)	0 / 46 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 97 (0.00%)	0 / 113 (0.00%)	0 / 46 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 97 (0.00%)	0 / 113 (0.00%)	0 / 46 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Small intestinal obstruction
subjects affected / exposed	0 / 97 (0.00%)	1 / 113 (0.88%)	0 / 46 (0.00%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Psoriasis
subjects affected / exposed	1 / 97 (1.03%)	0 / 113 (0.00%)	0 / 46 (0.00%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 97 (0.00%)	0 / 113 (0.00%)	0 / 46 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anxiety
subjects affected / exposed	0 / 97 (0.00%)	0 / 113 (0.00%)	0 / 46 (0.00%)	1 / 101 (0.99%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Homicidal ideation
subjects affected / exposed	1 / 97 (1.03%)	0 / 113 (0.00%)	0 / 46 (0.00%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	2 / 97 (2.06%)	0 / 113 (0.00%)	1 / 46 (2.17%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Schizophrenia
subjects affected / exposed	0 / 97 (0.00%)	3 / 113 (2.65%)	0 / 46 (0.00%)	2 / 101 (1.98%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Schizophrenia, paranoid type
subjects affected / exposed	0 / 97 (0.00%)	1 / 113 (0.88%)	0 / 46 (0.00%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	1 / 97 (1.03%)	0 / 113 (0.00%)	0 / 46 (0.00%)	0 / 101 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Asenapine 2.5 mg BID	Asenapine 5 mg BID	Olanzapine 15 mg QD	Placebo BID
Total subjects affected by non serious adverse events
subjects affected / exposed	27 / 97 (27.84%)	47 / 113 (41.59%)	17 / 46 (36.96%)	29 / 101 (28.71%)
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 97 (0.00%)	6 / 113 (5.31%)	0 / 46 (0.00%)	0 / 101 (0.00%)
occurrences all number	0	6	0	0
Nervous system disorders
Headache
subjects affected / exposed	10 / 97 (10.31%)	10 / 113 (8.85%)	4 / 46 (8.70%)	2 / 101 (1.98%)
occurrences all number	12	10	6	2
Somnolence
subjects affected / exposed	3 / 97 (3.09%)	7 / 113 (6.19%)	5 / 46 (10.87%)	0 / 101 (0.00%)
occurrences all number	3	7	5	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 97 (0.00%)	2 / 113 (1.77%)	3 / 46 (6.52%)	2 / 101 (1.98%)
occurrences all number	0	2	3	2
Dry mouth
subjects affected / exposed	0 / 97 (0.00%)	2 / 113 (1.77%)	5 / 46 (10.87%)	1 / 101 (0.99%)
occurrences all number	0	2	5	1
Dyspepsia
subjects affected / exposed	1 / 97 (1.03%)	2 / 113 (1.77%)	3 / 46 (6.52%)	2 / 101 (1.98%)
occurrences all number	1	2	3	2
Hypoaesthesia oral
subjects affected / exposed	4 / 97 (4.12%)	7 / 113 (6.19%)	0 / 46 (0.00%)	0 / 101 (0.00%)
occurrences all number	4	7	0	0
Psychiatric disorders
Agitation
subjects affected / exposed	3 / 97 (3.09%)	7 / 113 (6.19%)	0 / 46 (0.00%)	3 / 101 (2.97%)
occurrences all number	3	8	0	3
Anxiety
subjects affected / exposed	7 / 97 (7.22%)	8 / 113 (7.08%)	4 / 46 (8.70%)	12 / 101 (11.88%)
occurrences all number	10	9	5	13
Insomnia
subjects affected / exposed	9 / 97 (9.28%)	17 / 113 (15.04%)	4 / 46 (8.70%)	14 / 101 (13.86%)
occurrences all number	9	21	4	20
Schizophrenia
subjects affected / exposed	6 / 97 (6.19%)	4 / 113 (3.54%)	0 / 46 (0.00%)	4 / 101 (3.96%)
occurrences all number	6	4	0	4

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Were there any global substantial amendments to the protocol? Yes

14 Nov 2012

Amendment 01: Primary reason for amendment was to incorporate revisions to eligibility criteria, drug packaging/labeling and dosing instructions, list of events requiring discontinuation of subject from trial, schedule of assessments and statistical analysis, and to remove text stating that a Data Safety Monitoring Board would participate in study. Original base protocol and Amendments 01 and 02 were submitted together to country authority (Croatia health ministry) that provided approval.

14 Nov 2012

Amendment 02: Primary reason for amendment was to incorporate revisions to medications/treatments prohibited prior to and during trial, safety assessments, list of events defined to be serious adverse events, list of closely monitored events and procedures for liver enzyme monitoring. Original base protocol and Amendments 01 and 02 were submitted together to country authority (Croatia health ministry) that provided approval.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Olanzapine as an Active Control in Subjects With an Acute Exacerbation of Schizophrenia (Phase 3B, Protocol P05688 [formerly 041038]).

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline in PANSS Total Score at Day 42

Primary: Change From Baseline in PANSS Total Score at Day 42

Secondary: Change From Baseline in CGI-S Score at Day 42

Secondary: Change From Baseline in CGI-S Score at Day 42

Secondary: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42

Secondary: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42

Secondary: Change From Baseline in Body Weight at Day 42

Secondary: Change From Baseline in Body Weight at Day 42

Secondary: Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35

Secondary: Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35

Secondary: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35

Secondary: Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35

Secondary: Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35

Secondary: Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35

Secondary: Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Secondary: Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Olanzapine as an Active Control in Subjects With an Acute Exacerbation of Schizophrenia (Phase 3B, Protocol P05688 [formerly 041038]).