A Study of the Efficacy and Safety of Asenapine in Participants With an Acute Exacerbation of Schizophrenia (P05688)
Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT01617187
Collaborator
(none)
360
4
21.2
Study Details
Study Description
Brief Summary
The purpose of this trial is to assess the effect of asenapine 2.5 and 5 mg sublingually twice daily (BID) compared with placebo in the 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. The primary hypothesis is that at least one of the asenapine doses is superior to placebo in improving schizophrenia symptoms as measured by the change from Baseline in the 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 the 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 the rate of PANSS responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The trial consists of a screening/tapering period, treatment period, and follow-up period. The 6-week active treatment period includes an inpatient phase and outpatient phase. Participants who complete the trial may continue treatment under a long-term extension protocol (P05689). Participants who do not continue in the treatment continuation trial (whether they complete the 6-week trial or discontinue prematurely) will have a follow-up visit 7 days after their last dose of trial medication.
Study Design
Study Type:
Interventional
Actual Enrollment
:
360 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date
:
Dec 4, 2012
Actual Primary Completion Date
:
Aug 11, 2014
Actual Study Completion Date
:
Sep 9, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Asenapine 2.5 mg BID
|
Drug: Asenapine
2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually
Drug: Placebo Olanzapine
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
|
| Experimental: Asenapine 5 mg BID
|
Drug: Asenapine
2.5 mg or 5 mg fast dissolving active asenapine tablets administered sublingually
Drug: Placebo Olanzapine
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
|
| Active Comparator: Olanzapine 15 mg QD
|
Drug: Placebo Asenapine
Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually
Drug: Olanzapine
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
Drug: Placebo Olanzapine
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
|
| Placebo Comparator: Placebo BID
|
Drug: Placebo Asenapine
Fast dissolving placebo asenapine tablets (to match 2.5 mg and 5 mg active asenapine tablets) administered sublingually
Drug: Placebo Olanzapine
Film-coated placebo olanzapine tablets (to match 5 and 10 mg active olanzapine tablets) administered orally
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in PANSS Total Score at Day 42 [Baseline and Day 42]
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.
Secondary Outcome Measures
- Change From Baseline in CGI-S Score at Day 42 [Baseline and Day 42]
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.
- Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42 [Baseline and Day 42]
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).
- Change From Baseline in Body Weight at Day 42 [Baseline and Day 42]
Change from baseline in body weight at Day 42 is the Key Safety Outcome Measure.
- Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35 [Baseline and Days 4, 7, 14, 21, 28 and 35]
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.
- Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Days 4, 7, 14, 21, 28 and 35 [Days 4, 7, 14, 21, 28 and 35]
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.
- Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35 [Baseline and Days 4, 7, 14, 21, 28 and 35]
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.
- Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42 [Days 4, 7, 14, 21, 28, 35 and 42]
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.
- Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42 [Baseline and Days 4, 7, 14, 21, 28, 35 and 42]
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.
- Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42 [Baseline and Days 4, 7, 14, 21, 28, 35 and 42]
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.
- Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42 [Baseline and Days 4, 7, 14, 21, 28, 35 and 42]
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.
- Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 [Baseline and Days 4, 7, 14, 21, 28, 35 and 42]
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.
- Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 [Baseline and Days 4, 7, 14, 21, 28, 35 and 42]
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.
- Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 [Baseline and Days 4, 7, 14, 21, 28, 35 and 42]
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.
- Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 [Baseline and Days 4, 7, 14, 21, 28, 35 and 42]
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.
- Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 [Baseline and Days 4, 7, 14, 21, 28, 35 and 42]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Current diagnosis of schizophrenia of paranoid, disorganized, or undifferentiated subtype
-
Minimum PANSS total score of 70 at Screening and Baseline
-
Score of at least 4 (moderate) in two or more of the five items in the positive subscale of the PANSS
-
Confirmed to be experiencing an acute exacerbation of schizophrenia
-
CGI-S scale score of at least 4 (moderately ill) at Baseline
-
Has responded positively to an antipsychotic medication other than clozapine (Clozaril®) in a prior episode
Exclusion Criteria:
-
Body mass index (BMI) <18.5 or >40.0 kg/m^2
-
Laboratory and/or clinical evidence of clinically significant hepatic conditions
-
Known history of, or undergoing treatment for, narrow angle glaucoma
-
Diagnosed with epilepsy or has had any seizure disorder beyond childhood febrile seizures
-
Known serological evidence of human immunodeficiency virus (HIV) antibody
-
History of neuroleptic malignant syndrome or tardive dyskinesias
-
Past or current diagnosis of schizoaffective disorder, schizophrenia of residual subtype, schizophrenia of catatonic subtype, current diagnosis of schizophrenia with course specifiers continuous, single episode in partial remission, or single episode in full remission, or borderline personality disorder
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organon and Co
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT01617187
Other Study ID Numbers:
- P05688
- 2010-018407-28
First Posted:
Jun 12, 2012
Last Update Posted:
Feb 9, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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 Participant Flow table, this participant is presented as Not Completed in period "Randomization through Start Treatment" (Not Treated). |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet twice daily (BID) for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | Participants were administered 15 mg olanzapine (as one 10 mg and one 5 mg tablet) once daily (QD) for 42 days, except during Week 1 olanzapine 10 mg QD was administered | Participants were administered placebo tablets BID for 42 days |
| Period Title: Randomization Through Start Treatment | ||||
| STARTED | 98 | 113 | 46 | 103 |
| COMPLETED | 97 | 113 | 46 | 101 |
| NOT COMPLETED | 1 | 0 | 0 | 2 |
| Period Title: Randomization Through Start Treatment | ||||
| STARTED | 97 | 113 | 46 | 101 |
| COMPLETED | 86 | 102 | 41 | 91 |
| NOT COMPLETED | 11 | 11 | 5 | 10 |
Baseline Characteristics
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days | Total of all reporting groups |
| Overall Participants | 97 | 113 | 46 | 101 | 357 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
41.5
(10.79)
|
39.1
(10.68)
|
40.8
(11.15)
|
41.4
(12.05)
|
40.6
(11.18)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
39
40.2%
|
44
38.9%
|
18
39.1%
|
47
46.5%
|
148
41.5%
|
| Male |
58
59.8%
|
69
61.1%
|
28
60.9%
|
54
53.5%
|
209
58.5%
|
| Positive and Negative Syndrome Scale (PANSS) total score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
93.3
(11.10)
|
95.8
(13.77)
|
92.7
(10.47)
|
93.4
(11.16)
|
94.1
(11.97)
|
| Clinical Global Impression Scale-Severity (CGI-S) score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
4.8
(0.64)
|
4.9
(0.64)
|
4.8
(0.61)
|
4.8
(0.61)
|
4.8
(0.63)
|
| Body Weight (kg) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kg] |
81.6
(17.73)
|
78.6
(17.88)
|
80.7
(17.79)
|
77.1
(17.56)
|
79.3
(17.75)
|
| PANSS negative subscale score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
23.5
(4.47)
|
24.1
(4.50)
|
23.4
(3.96)
|
23.9
(4.22)
|
23.8
(4.34)
|
| PANSS positive subscale score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
24.4
(4.05)
|
25.5
(4.76)
|
24.6
(3.46)
|
24.6
(3.88)
|
24.8
(4.19)
|
| PANSS general psychopathology subscale score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
45.5
(6.05)
|
46.3
(6.87)
|
44.7
(6.20)
|
44.9
(6.05)
|
45.5
(6.34)
|
| PANSS Marder factor positive symptom score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
29.3
(5.02)
|
30.0
(5.05)
|
29.0
(4.69)
|
29.4
(4.36)
|
29.5
(4.80)
|
| PANSS Marder factor negative symptom score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
22.6
(4.30)
|
23.0
(4.66)
|
23.0
(4.44)
|
22.8
(4.76)
|
22.8
(4.55)
|
| PANSS Marder factor disorganized thought symptom score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
21.5
(4.32)
|
22.6
(4.93)
|
21.2
(4.29)
|
21.6
(4.42)
|
21.8
(4.56)
|
| PANSS Marder factor hostility/excitement symptom score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
9.0
(2.99)
|
9.4
(3.49)
|
8.7
(3.11)
|
8.8
(3.22)
|
9.0
(3.23)
|
| PANSS Marder factor anxiety/depression symptom score (score on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [score on a scale] |
11.0
(2.97)
|
10.9
(3.13)
|
10.9
(3.62)
|
10.7
(2.96)
|
10.9
(3.09)
|
Outcome Measures
| Title | Change From Baseline in PANSS Total Score at Day 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Day 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Least Squares Mean (Standard Error) [score on a scale] |
-17.4
(1.80)
|
-21.7
(1.60)
|
-21.6
(2.32)
|
-16.2
(1.71)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6043 |
| Comments | Adjusted p-value from graphical approach to control Type 1 error rate among primary and secondary efficacy hypotheses | |
| Method | Mixed Model Repeated Measures (MMRM) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares (LS) means difference |
| Estimated Value | -1.3 | |
| Confidence Interval |
(2-Sided) 95% -6.1 to 3.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.46 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0356 |
| Comments | Adjusted p-value from graphical approach to control Type 1 error rate among primary and secondary efficacy hypotheses | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -5.5 | |
| Confidence Interval |
(2-Sided) 95% -10.1 to -1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.32 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0587 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -5.4 | |
| Confidence Interval |
(2-Sided) 95% -11.1 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.86 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in CGI-S Score at Day 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Day 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Least Squares Mean (Standard Error) [score on a scale] |
-0.9
(0.11)
|
-1.2
(0.10)
|
-1.1
(0.14)
|
-1.0
(0.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | 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 (Primary outcome measure) | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9083 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | 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 (Primary outcome measure) | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0601 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3898 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.18 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Percentage of Participants Who Are PANSS Responders (≥30% Reduction From Baseline in PANSS Total Score) at Day 42 |
|---|---|
| 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). |
| Time Frame | Baseline and Day 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Number [percentage of participants] |
14.6
(0.11)
15.1%
|
25.2
(0.10)
22.3%
|
26.7
(0.14)
58%
|
19.2
(0.11)
19%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | 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 (Primary outcome measure) | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3700 |
| Comments | P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | 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 (Primary outcome measure) | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1708 |
| Comments | P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2620 |
| Comments | P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Change From Baseline in Body Weight at Day 42 |
|---|---|
| Description | Change from baseline in body weight at Day 42 is the Key Safety Outcome Measure. |
| Time Frame | Baseline and Day 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received ≥1 dose of study drug |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 97 | 113 | 46 | 101 |
| Least Squares Mean (Standard Error) [kg] |
1.3
(0.38)
|
1.3
(0.33)
|
2.4
(0.47)
|
0.3
(0.35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Olanzapine 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0491 |
| Comments | p-value adjusted for multiple comparisons using Hochberg's method | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to -0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.60 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Olanzapine 15 mg QD | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Olanzapine 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0491 |
| Comments | p-value adjusted for multiple comparisons using Hochberg's method | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to -0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | Asenapine 5 mg BID minus Olanzapine 15 mg QD | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0567 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 1.0 | |
| Confidence Interval |
(2-Sided) 95% -0.0 to 2.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0391 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 1.0 | |
| Confidence Interval |
(2-Sided) 95% 0.0 to 1.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.48 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 2.2 | |
| Confidence Interval |
(2-Sided) 95% 1.0 to 3.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in PANSS Total Score at Days 4, 7, 14, 21, 28 and 35 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28 and 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 |
-4.0
(0.80)
|
-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
(1.80)
|
-10.7
(1.28)
|
| Day 21 |
-12.0
(1.55)
|
-14.8
(1.40)
|
-15.2
(2.09)
|
-13.2
(1.50)
|
| Day 28 |
-12.3
(1.69)
|
-17.1
(1.49)
|
-17.3
(2.21)
|
-15.5
(1.61)
|
| Day 35 |
-17.0
(1.66)
|
-19.0
(1.48)
|
-20.3
(2.19)
|
-15.4
(1.58)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4849 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.8 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 2.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.09 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8902 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -2.2 to 1.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.06 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5826 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -3.4 to 1.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.36 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9271 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -3.3 to 3.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.61 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1902 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -5.1 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.56 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2710 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -2.2 | |
| Confidence Interval |
(2-Sided) 95% -6.2 to 1.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.00 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6773 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -2.8 to 4.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.79 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2895 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -5.2 to 1.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.72 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4261 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.7 | |
| Confidence Interval |
(2-Sided) 95% -6.0 to 2.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.18 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5505 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to 5.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.13 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4286 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -5.6 to 2.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.03 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4423 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -7.0 to 3.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.56 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1691 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 3.2 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 7.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.30 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4682 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -5.8 to 2.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.17 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4961 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -7.2 to 3.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.71 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4697 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -6.1 to 2.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.26 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0947 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -3.6 | |
| Confidence Interval |
(2-Sided) 95% -7.8 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.14 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0675 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -4.9 | |
| Confidence Interval |
(2-Sided) 95% -10.2 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 2.68 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| 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 |
|---|---|
| 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. |
| Time Frame | Days 4, 7, 14, 21, 28 and 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 (n = 95,108,44,97) |
0.0
(0.27)
0%
|
0.0
(0.25)
0%
|
0.0
(0.38)
0%
|
2.1
(0.27)
2.1%
|
| Day 7 (n = 96,111,45,99) |
2.1
(0.30)
2.2%
|
5.4
(0.28)
4.8%
|
0.0
(0.43)
0%
|
5.1
(0.30)
5%
|
| Day 14 (n = 96,111,45,99) |
5.2
(0.31)
5.4%
|
5.4
(0.28)
4.8%
|
4.4
(0.42)
9.6%
|
7.1
(0.30)
7%
|
| Day 21 (n = 96,111,45,99) |
8.3
(0.32)
8.6%
|
14.4
(0.29)
12.7%
|
11.1
(0.42)
24.1%
|
13.1
(0.31)
13%
|
| Day 28 (n = 96,111,45,99) |
10.4
(0.36)
10.7%
|
16.2
(0.32)
14.3%
|
15.6
(0.47)
33.9%
|
14.1
(0.35)
14%
|
| Day 35 (n = 96,111,45,99) |
15.6
(0.34)
16.1%
|
21.6
(0.30)
19.1%
|
15.6
(0.44)
33.9%
|
17.2
(0.32)
17%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1736 |
| Comments | P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1736 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2850 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3290 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6938 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1105 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6804 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9704 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6604 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2447 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4834 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9189 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4370 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2894 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6953 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4892 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1954 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7990 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Change From Baseline in CGI-S Score at Days 4, 7, 14, 21, 28 and 35 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28 and 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| 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
(0.10)
|
-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
(0.10)
|
-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
(0.10)
|
| Day 35 |
-0.9
(0.11)
|
-1.1
(0.10)
|
-1.0
(0.14)
|
-0.8
(0.10)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4255 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.07 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9564 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.06 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6363 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8759 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.10 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9598 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.09 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9789 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.12 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4671 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6359 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.11 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5454 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4188 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.13 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5318 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.13 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5683 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.16 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2972 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4820 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.13 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9901 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.17 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6682 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.15 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1111 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.14 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2400 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.17 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Percentage of Participants Who Are Clinical Global Impression Scale-Improvement (CGI-I) Responders at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 (n = 95,108,44,98) |
34.7
(0.27)
35.8%
|
33.3
(0.25)
29.5%
|
43.2
(0.38)
93.9%
|
37.8
(0.27)
37.4%
|
| Day 7 (n = 96,111,45,99) |
51.0
(0.30)
52.6%
|
46.8
(0.28)
41.4%
|
60.0
(0.43)
130.4%
|
45.5
(0.30)
45%
|
| Day 14 (n = 96,111,45,99) |
51.0
(0.31)
52.6%
|
60.4
(0.28)
53.5%
|
71.1
(0.42)
154.6%
|
54.5
(0.30)
54%
|
| Day 21 (n = 96,111,45,99) |
54.2
(0.32)
55.9%
|
63.1
(0.29)
55.8%
|
75.6
(0.42)
164.3%
|
58.6
(0.31)
58%
|
| Day 28 (n = 96,111,45,99) |
58.3
(0.36)
60.1%
|
62.2
(0.32)
55%
|
73.3
(0.47)
159.3%
|
60.6
(0.35)
60%
|
| Day 35 (n = 96,111,45,99) |
60.4
(0.34)
62.3%
|
64.0
(0.30)
56.6%
|
82.2
(0.44)
178.7%
|
64.6
(0.32)
64%
|
| Day 42 (n = 96,111,45,99) |
59.4
(0.40)
61.2%
|
66.7
(0.35)
59%
|
84.4
(0.50)
183.5%
|
62.6
(0.38)
62%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6205 |
| Comments | P-value from Cochran Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4829 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3945 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4076 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9690 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1170 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5088 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3426 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0762 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5531 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4875 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0692 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7482 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8037 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0859 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5850 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9698 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0132 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7129 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5074 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0040 |
| Comments | P-value from Cochran-Mantel-Haenszel test with an adjustment for pooled center | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Change From Baseline in PANSS Negative Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| 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
(0.56)
|
-2.3
(0.40)
|
| Day 28 |
-2.5
(0.45)
|
-3.1
(0.40)
|
-2.6
(0.59)
|
-3.0
(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)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8829 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.40 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5488 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.39 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7830 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8070 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.45 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5280 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.44 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4025 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6471 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 1.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2504 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.49 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9223 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 1.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8839 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 1.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.56 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8077 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6216 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 1.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.68 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4248 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.5 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 1.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7667 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6282 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 1.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3150 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.9 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1908 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3128 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.77 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8812 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to 1.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1143 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4418 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.84 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in PANSS Positive Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 |
-1.2
(0.29)
|
-1.6
(0.28)
|
-2.3
(0.42)
|
-1.7
(0.30)
|
| 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
(0.40)
|
-4.4
(0.61)
|
-3.7
(0.43)
|
| Day 21 |
-4.0
(0.52)
|
-5.0
(0.47)
|
-5.7
(0.70)
|
-4.5
(0.51)
|
| Day 28 |
-4.1
(0.59)
|
-5.7
(0.52)
|
-6.2
(0.77)
|
-5.0
(0.56)
|
| Day 35 |
-5.2
(0.60)
|
-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)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2160 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.5 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 1.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.40 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9494 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.39 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1834 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6347 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 1.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6917 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1431 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6267 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 1.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7260 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3326 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -2.2 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.74 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4575 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.5 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 1.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4930 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.8 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.68 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1886 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -2.8 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.86 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2643 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.9 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 2.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.80 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3516 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -2.2 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.76 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2068 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.94 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7284 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 1.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.82 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2698 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.77 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1510 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.4 | |
| Confidence Interval |
(2-Sided) 95% -3.3 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8039 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 1.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.88 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0306 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -3.5 to -0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0406 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -2.1 | |
| Confidence Interval |
(2-Sided) 95% -4.1 to -0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.03 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in PANSS General Psychopathology Subscale Score at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 |
-2.2
(0.49)
|
-2.7
(0.46)
|
-2.5
(0.70)
|
-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
(1.00)
|
-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
(0.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7819 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 1.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7030 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9520 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to 1.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7907 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to 1.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.95 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1391 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.4 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.91 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4901 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 1.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.18 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8079 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to 2.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.00 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3889 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -2.7 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.95 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3907 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -3.4 to 1.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.21 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5363 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to 3.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.15 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5075 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to 1.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.09 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4526 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -3.7 to 1.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.38 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1548 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 1.8 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 4.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.26 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6589 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to 1.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.19 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5171 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -3.9 to 2.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.48 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3133 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -3.6 to 1.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.20 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1723 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -3.8 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.13 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0663 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -2.6 | |
| Confidence Interval |
(2-Sided) 95% -5.4 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.42 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5128 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -3.5 to 1.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.32 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0842 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -2.2 | |
| Confidence Interval |
(2-Sided) 95% -4.6 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.24 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1217 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -2.4 | |
| Confidence Interval |
(2-Sided) 95% -5.4 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.52 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in PANSS Marder Factor Positive Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 |
-1.3
(0.29)
|
-1.8
(0.27)
|
-2.0
(0.41)
|
-2.0
(0.29)
|
| Day 7 |
-2.5
(0.41)
|
-2.9
(0.38)
|
-3.2
(0.58)
|
-2.8
(0.40)
|
| Day 14 |
-3.9
(0.49)
|
-4.0
(0.44)
|
-4.4
(0.67)
|
-4.1
(0.47)
|
| Day 21 |
-4.5
(0.55)
|
-5.4
(0.50)
|
-5.5
(0.74)
|
-5.1
(0.54)
|
| Day 28 |
-4.8
(0.60)
|
-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)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0584 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -0.0 to 1.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.39 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5197 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.38 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9693 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.49 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6161 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 1.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.56 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7880 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5526 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -1.8 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7647 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 1.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.67 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8900 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 1.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.64 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7097 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.9 to 1.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.81 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4601 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 2.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.76 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6288 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.8 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6099 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to 1.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.91 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2790 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.9 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 2.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.82 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4253 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.77 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3014 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -2.9 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.96 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9720 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to 1.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.87 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4758 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -2.2 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.82 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4419 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -2.8 to 1.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.03 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4762 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.91 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1046 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.4 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.86 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1411 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -3.7 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 1.06 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in PANSS Marder Factor Negative Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 |
-1.2
(0.30)
|
-0.8
(0.28)
|
-0.8
(0.43)
|
-0.7
(0.30)
|
| Day 7 |
-1.7
(0.37)
|
-1.9
(0.34)
|
-1.8
(0.53)
|
-1.3
(0.37)
|
| Day 14 |
-2.0
(0.41)
|
-2.8
(0.37)
|
-2.2
(0.56)
|
-2.0
(0.40)
|
| Day 21 |
-2.6
(0.44)
|
-3.2
(0.40)
|
-2.6
(0.60)
|
-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
(0.49)
|
| Day 42 |
-3.4
(0.53)
|
-4.7
(0.47)
|
-4.3
(0.67)
|
-4.0
(0.51)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2754 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.40 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8500 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.39 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8439 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4741 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2158 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.49 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5060 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.63 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9956 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.56 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1624 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.8 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7662 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.68 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8363 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.61 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2388 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.8 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9435 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to 1.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.73 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4267 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 1.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6810 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7673 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 1.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.82 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4830 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.9 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.70 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2128 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1756 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -2.8 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4246 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 2.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.72 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2873 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.68 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7308 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.9 to 1.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.83 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 |
-0.3
(0.24)
|
-0.7
(0.22)
|
-1.1
(0.34)
|
-0.7
(0.24)
|
| Day 7 |
-1.0
(0.32)
|
-1.4
(0.29)
|
-1.6
(0.45)
|
-0.7
(0.31)
|
| Day 14 |
-1.3
(0.36)
|
-2.0
(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
(0.40)
|
| 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
(0.40)
|
-4.7
(0.58)
|
-2.7
(0.43)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2116 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.32 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9039 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.31 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2959 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.4 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5909 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.44 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1489 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.42 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1000 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.9 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7830 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.49 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2679 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.47 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2321 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.9 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.60 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7368 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.56 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4606 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3241 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.66 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9860 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1890 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.8 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3030 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.67 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0550 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to 0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0415 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -2.2 to -0.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.55 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0058 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.9 | |
| Confidence Interval |
(2-Sided) 95% -3.3 to -0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.69 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0691 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0063 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -2.7 to -0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0056 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -2.0 | |
| Confidence Interval |
(2-Sided) 95% -3.4 to -0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.71 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| 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
(0.40)
|
-0.7
(0.28)
|
| Day 14 |
-0.9
(0.30)
|
-0.8
(0.27)
|
-1.2
(0.41)
|
-0.9
(0.30)
|
| Day 21 |
-0.8
(0.33)
|
-0.9
(0.30)
|
-1.8
(0.44)
|
-1.0
(0.32)
|
| Day 28 |
-0.5
(0.41)
|
-0.8
(0.36)
|
-1.6
(0.53)
|
-1.0
(0.39)
|
| Day 35 |
-1.4
(0.37)
|
-1.5
(0.32)
|
-2.0
(0.47)
|
-1.4
(0.35)
|
| Day 42 |
-1.1
(0.41)
|
-1.8
(0.36)
|
-1.9
(0.52)
|
-1.1
(0.39)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7847 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.34 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5859 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.33 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6413 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.43 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7307 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.38 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7176 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.37 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4860 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.48 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9321 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.41 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7691 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.39 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5694 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5583 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 1.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.45 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7307 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.43 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1715 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.8 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4219 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 1.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.55 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7437 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 1.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3110 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.9 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.65 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9805 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.50 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8741 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.47 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3288 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.58 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9336 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.56 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1722 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1909 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -2.1 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.64 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
| Title | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score at Days 4, 7, 14, 21, 28, 35 and 42 |
|---|---|
| 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. |
| Time Frame | Baseline and Days 4, 7, 14, 21, 28, 35 and 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS, defined as randomized participants who received ≥1 dose of study drug and had both a baseline and ≥1 post-baseline PANSS Total Score |
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days |
| Measure Participants | 96 | 111 | 45 | 99 |
| Day 4 |
-0.9
(0.27)
|
-1.2
(0.25)
|
-1.0
(0.38)
|
-0.9
(0.27)
|
| Day 7 |
-1.5
(0.30)
|
-2.2
(0.28)
|
-1.8
(0.43)
|
-1.7
(0.30)
|
| Day 14 |
-1.9
(0.31)
|
-2.9
(0.28)
|
-2.5
(0.42)
|
-2.5
(0.30)
|
| Day 21 |
-2.1
(0.32)
|
-3.0
(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
(0.34)
|
-3.6
(0.30)
|
-3.2
(0.44)
|
-3.2
(0.32)
|
| Day 42 |
-2.9
(0.40)
|
-3.4
(0.35)
|
-3.1
(0.50)
|
-3.0
(0.38)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9851 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.37 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4912 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.9 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.36 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8559 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.46 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5635 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.41 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2321 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.40 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8867 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1499 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 1.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.42 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2860 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.40 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 14 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8978 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0283 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 1.0 | |
| Confidence Interval |
(2-Sided) 95% 0.1 to 1.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.44 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8667 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.41 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 21 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5044 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 1.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.52 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0040 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% 0.5 to 2.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.49 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6330 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.46 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 28 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2981 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.6 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 1.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.57 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6556 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.45 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2889 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.3 to 0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.43 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 35 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9399 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.0 | |
| Confidence Interval |
(2-Sided) 95% -1.1 to 1.0 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.53 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 2.5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8955 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.0 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.54 |
|
| Estimation Comments | Asenapine 2.5 mg BID minus Placebo BID | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Asenapine 5 mg BID, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3681 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.51 |
|
| Estimation Comments | Asenapine 5 mg BID minus Placebo BID | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Olanzapine 15 mg QD, Placebo BID |
|---|---|---|
| Comments | Day 42 | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8215 |
| Comments | Unadjusted p-value | |
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -1.4 to 1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.62 |
|
| Estimation Comments | Olanzapine 15 mg BID minus Placebo BID | |
Adverse Events
| Time Frame | Up to 30 days after last dose of study drug (Up to approximately 10 weeks) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID | ||||
| Arm/Group Description | Participants were administered one 2.5 mg asenapine tablet BID for 42 days | Participants were administered one 5 mg asenapine tablet BID for 42 days | 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 | Participants were administered placebo tablets BID for 42 days | ||||
All Cause Mortality |
||||||||
| Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/97 (5.2%) | 5/113 (4.4%) | 1/46 (2.2%) | 8/101 (7.9%) | ||||
| Gastrointestinal disorders | ||||||||
| Small intestinal obstruction | 0/97 (0%) | 0 | 1/113 (0.9%) | 1 | 0/46 (0%) | 0 | 0/101 (0%) | 0 |
| General disorders | ||||||||
| Chest pain | 0/97 (0%) | 0 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 1/101 (1%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Road traffic accident | 0/97 (0%) | 0 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 1/101 (1%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Diabetes mellitus | 1/97 (1%) | 1 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 0/101 (0%) | 0 |
| Nervous system disorders | ||||||||
| Epilepsy | 0/97 (0%) | 0 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 1/101 (1%) | 1 |
| Syncope | 0/97 (0%) | 0 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 1/101 (1%) | 1 |
| Psychiatric disorders | ||||||||
| Agitation | 0/97 (0%) | 0 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 1/101 (1%) | 1 |
| Anxiety | 0/97 (0%) | 0 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 1/101 (1%) | 1 |
| Homicidal ideation | 1/97 (1%) | 1 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 0/101 (0%) | 0 |
| Psychotic disorder | 2/97 (2.1%) | 2 | 0/113 (0%) | 0 | 1/46 (2.2%) | 1 | 0/101 (0%) | 0 |
| Schizophrenia | 0/97 (0%) | 0 | 3/113 (2.7%) | 3 | 0/46 (0%) | 0 | 2/101 (2%) | 2 |
| Schizophrenia, paranoid type | 0/97 (0%) | 0 | 1/113 (0.9%) | 1 | 0/46 (0%) | 0 | 0/101 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Psoriasis | 1/97 (1%) | 1 | 0/113 (0%) | 0 | 0/46 (0%) | 0 | 0/101 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Asenapine 2.5 mg BID | Asenapine 5 mg BID | Olanzapine 15 mg QD | Placebo BID | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/97 (27.8%) | 47/113 (41.6%) | 17/46 (37%) | 29/101 (28.7%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 0/97 (0%) | 0 | 2/113 (1.8%) | 2 | 3/46 (6.5%) | 3 | 2/101 (2%) | 2 |
| Dry mouth | 0/97 (0%) | 0 | 2/113 (1.8%) | 2 | 5/46 (10.9%) | 5 | 1/101 (1%) | 1 |
| Dyspepsia | 1/97 (1%) | 1 | 2/113 (1.8%) | 2 | 3/46 (6.5%) | 3 | 2/101 (2%) | 2 |
| Hypoaesthesia oral | 4/97 (4.1%) | 4 | 7/113 (6.2%) | 7 | 0/46 (0%) | 0 | 0/101 (0%) | 0 |
| Investigations | ||||||||
| Blood creatine phosphokinase increased | 0/97 (0%) | 0 | 6/113 (5.3%) | 6 | 0/46 (0%) | 0 | 0/101 (0%) | 0 |
| Nervous system disorders | ||||||||
| Headache | 10/97 (10.3%) | 12 | 10/113 (8.8%) | 10 | 4/46 (8.7%) | 6 | 2/101 (2%) | 2 |
| Somnolence | 3/97 (3.1%) | 3 | 7/113 (6.2%) | 7 | 5/46 (10.9%) | 5 | 0/101 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Agitation | 3/97 (3.1%) | 3 | 7/113 (6.2%) | 8 | 0/46 (0%) | 0 | 3/101 (3%) | 3 |
| Anxiety | 7/97 (7.2%) | 10 | 8/113 (7.1%) | 9 | 4/46 (8.7%) | 5 | 12/101 (11.9%) | 13 |
| Insomnia | 9/97 (9.3%) | 9 | 17/113 (15%) | 21 | 4/46 (8.7%) | 4 | 14/101 (13.9%) | 20 |
| Schizophrenia | 6/97 (6.2%) | 6 | 4/113 (3.5%) | 4 | 0/46 (0%) | 0 | 4/101 (4%) | 4 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
It is planned to first publish/present trial results together with the other sites, unless permission is obtained from Sponsor to publish separate results. Sponsor must be able to review all proposed results communications regarding study 45 days prior to submission for publication/presentation. If there is disagreement concerning appropriateness of the materials, Investigator and Sponsor must meet to make a good faith effort to discuss/resolve disagreement prior to submission for publication.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT01617187
Other Study ID Numbers:
- P05688
- 2010-018407-28
First Posted:
Jun 12, 2012
Last Update Posted:
Feb 9, 2022
Last Verified:
Feb 1, 2022