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Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder (P06107 Has an Extension [P05898; NCT01349907])(P06107)

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ClinicalTrials.gov Identifier: NCT01244815
Recruitment Status : Completed
First Posted : November 19, 2010
Results First Posted : September 4, 2014
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Bipolar Disorder, Pediatric
Interventions Drug: asenapine
Drug: Placebo to match asenapine
Drug: Rescue medication
Enrollment 404

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description Participants receive placebo twice daily (BID) for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Period Title: Overall Study
Started 101 [1] 105 [1] 99 [1] 99 [1]
Treated 101 104 99 99
Completed 87 88 88 87
Not Completed 14 17 11 12
Reason Not Completed
Not Treated             0             1             0             0
Adverse Event             4             7             5             5
Treatment Failure             0             0             0             1
Lost to Follow-up             3             2             3             2
Withdrawal by Subject             0             2             0             3
Protocol Violation             7             4             3             1
Did Not Meet Protocol Eligibility             0             1             0             0
[1]
Randomized
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID Total
Hide Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period. Total of all reporting groups
Overall Number of Baseline Participants 101 104 99 99 403
Hide Baseline Analysis Population Description
The population consisted of all randomized participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
13.7  (2.0) 13.7  (2.1) 13.8  (2.0) 13.9  (2.1) 13.8  (2.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
Female
63
  62.4%
52
  50.0%
56
  56.6%
41
  41.4%
212
  52.6%
Male
38
  37.6%
52
  50.0%
43
  43.4%
58
  58.6%
191
  47.4%
Young Mania Rating Scale (Y-MRS) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
29.9  (5.5) 29.5  (5.7) 30.3  (5.9) 30.2  (5.6) 30.0  (5.7)
[1]
Measure Description: Y-MRS is an 11-item instrument for assessing the severity of manic episodes. Seven of the 11 items are rated on a scale of 0-4 and 4 are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60. Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively.
Clinical Global Impression Scale for use in Bipolar Disorder (CGI-BP) overall score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
4.3  (0.5) 4.5  (0.6) 4.4  (0.6) 4.4  (0.6) 4.4  (0.6)
[1]
Measure Description: CGI-BP overall score is obtained using a 7-point scale assessing the severity of the participant’s overall bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. Summary statistics presented are for efficacy population (FAS): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively.
CGI-BP mania score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
4.3  (0.5) 4.5  (0.6) 4.4  (0.6) 4.4  (0.6) 4.4  (0.6)
[1]
Measure Description: CGI-BP mania score is obtained using a 7-point scale assessing the severity of the mania component of the participant’s bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. Summary statistics presented are for efficacy population (FAS): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively.
CGI-BP depression score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
2.9  (1.3) 2.8  (1.3) 2.9  (1.4) 2.8  (1.2) 2.8  (1.3)
[1]
Measure Description: CGI-BP depression score is obtained using a 7-point scale assessing the severity of the depression component of the participant’s bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. Summary statistics presented are for efficacy population (FAS) except as noted: N=97 (baseline value not available for 1 FAS participant in this group), 101, 98, 98 and 394 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively.
Children's Depression Rating Scale, Revised (CDRS-R) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
34.5  (10.2) 33.7  (9.0) 35.2  (11.9) 34.1  (9.0) 34.4  (10.1)
[1]
Measure Description: CDRS-R is a 17-item instrument for assessing depression in children. Items are rated on a scale of 1-7 (14 items) or 1-5 (3 items); higher scores indicate more severe symptoms. CDRS-R total score is sum of ratings for the 17 items (range: 17-113). Summary statistics presented are for efficacy population (FAS) except as noted: N=97 (baseline value not available for 1 FAS participant in this group), 99 (baseline value not available for 2 FAS participants in this group), 98, 98 and 392 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively.
Children’s Global Assessment Scale (CGAS) total score - current functioning   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
49.0  (7.9) 49.6  (7.4) 48.4  (7.4) 49.1  (6.7) 49.0  (7.4)
[1]
Measure Description: CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively.
Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
48.7  (9.7) 49.1  (9.6) 49.5  (9.1) 49.1  (10.5) 49.1  (9.7)
[1]
Measure Description: PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life on a scale of 1=very poor to 5=very good. The PQ-LES-Q total score (sum of Items 1-14) ranged from 14 to 70 with a higher score indicating better quality of life. Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively.
PQ-LES-Q overall score (i.e., item 15)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 101 participants 104 participants 99 participants 99 participants 403 participants
3.7  (1.0) 3.8  (1.0) 3.8  (0.9) 3.8  (1.0) 3.8  (1.0)
[1]
Measure Description: PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life on a scale of 1=very poor to 5=very good. The PQ-LES-Q overall score (Item 15, a global assessment of quality of life) ranged from 1 to 5 with a higher score indicating better quality of life. Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively.
1.Primary Outcome
Title Change From Baseline in Y-MRS Total Score at Day 21
Hide Description The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant’s subjective report of his or her condition over the previous 48 hours and the clinician’s observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
Time Frame Baseline and Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy Full Analysis Set [FAS]); also, to be included an on-treatment Day 21 value of Y-MRS total score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 79 88 87 81
Mean (Standard Deviation)
Unit of Measure: score on a scale
-9.6  (7.8) -12.3  (9.0) -15.1  (9.5) -15.9  (9.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments p-value is adjusted by Hochberg's method for testing three asenapine groups versus the placebo group
Method Mixed Model for Repeated Measures (MMRM)
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in Least Squares (LS) Means
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-5.6 to -0.8
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is adjusted by Hochberg's method for testing three asenapine groups versus the placebo group
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -5.3
Confidence Interval (2-Sided) 95%
-7.7 to -2.9
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is adjusted by Hochberg's method for testing three asenapine groups versus the placebo group
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-8.6 to -3.8
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 1 (Placebo<2.5 mg=5.0 mg=10.0 mg)
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter t-statistic
Estimated Value -4.92
Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 1. Lower value indicates pattern provides better fit to data.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 2 (Placebo=2.5 mg<5.0 mg=10.0 mg)
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter t-statistic
Estimated Value -4.87
Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 2. Lower value indicates pattern provides better fit to data.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 3 (Placebo=2.5 mg=5.0 mg<10.0 mg)
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter t-statistic
Estimated Value -3.40
Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 3. Lower value indicates pattern provides better fit to data.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 4 (Placebo<2.5 mg<5.0 mg<10.0 mg)
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter t-statistic
Estimated Value -5.28
Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 4. Lower value indicates pattern provides better fit to data.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 5 (Placebo=2.5 mg<5.0 mg<10.0 mg)
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter t-statistic
Estimated Value -4.64
Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 5. Lower value indicates pattern provides better fit to data.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 6 (Placebo<2.5 mg=5.0 mg<10.0 mg)
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter t-statistic
Estimated Value -5.07
Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 6. Lower value indicates pattern provides better fit to data.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID, Asenapine 5.0 mg BID, Asenapine 10.0 mg BID
Comments Investigation of dose-response relationship of change from baseline to Day 21 in Y-MRS total score was a Secondary study endpoint. Multiple contrast testing using MMRM model (FAS population) was used to evaluate 7 pre-defined dose-response patterns.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments p-value (adjusted to control Type I error in multiple testing) for dose-response pattern 7 (Placebo<2.5 mg<5.0 mg=10.0 mg)
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter t-statistic
Estimated Value -5.49
Estimation Comments t-statistic associated with the contrast of the MMRM model for dose-response pattern 7. Lower value indicates pattern provides better fit to data.
2.Secondary Outcome
Title Change From Baseline in Clinical Global Impression Scale for Use in Bipolar Disorder (CGI-BP) Overall Score at Day 21
Hide Description Change from baseline in CGI-BP overall score at Day 21 is the Key Secondary Outcome Measure. The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the participant’s overall bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
Time Frame Baseline and Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP overall score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 79 88 87 81
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.7  (0.9) -1.3  (1.1) -1.4  (1.0) -1.4  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is adjusted by Hochberg's method for testing three asenapine groups versus the placebo group
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-0.9 to -0.3
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is adjusted by Hochberg's method for testing three asenapine groups versus the placebo group
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-0.9 to -0.4
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value is adjusted by Hochberg's method for testing three asenapine groups versus the placebo group
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.0 to -0.4
Estimation Comments Estimate is asenapine versus placebo
3.Secondary Outcome
Title Total Y-MRS 50% Responders at Days 4, 7, 14 and 21
Hide Description A total Y-MRS 50% responder was defined as a participant who had a reduction from baseline to the identified study visit of at least 50% in the Y-MRS total score. The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items, based on the participant’s subjective report of his or her condition over the previous 48 hours and the clinician’s observations during the interview, with the emphasis on the latter. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60 with higher scores indicating greater severity of symptoms. This analysis used a Last-Observation-Carried-Forward (LOCF) approach; if at a given visit no Y-MRS total score was available for determining whether a participant was a responder, the last available post-baseline on-treatment assessment prior to that visit was used.
Time Frame Baseline and Days 4, 7, 14 and 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included for a visit, a Y-MRS total score must be available for that visit or a prior post-baseline on-treatment visit
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 98 101 98 98
Measure Type: Number
Unit of Measure: participants
Day 4 (n=95, 98, 93, 90) 7 19 20 13
Day 7 (n=98, 101, 98, 98) 14 33 31 37
Day 14 (n=98, 101, 98, 98) 20 36 50 50
Day 21 (n=98, 101, 98, 98) 27 42 53 51
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Analysis is for asenapine versus placebo on Day 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
1.2 to 7.6
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Analysis is for asenapine versus placebo on Day 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.4
Confidence Interval (2-Sided) 95%
1.4 to 8.6
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Analysis is for asenapine versus placebo on Day 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.129
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
0.8 to 5.6
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Analysis is for asenapine versus placebo on Day 7 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
1.4 to 5.9
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Analysis is for asenapine versus placebo on Day 7 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
1.4 to 5.6
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Analysis is for asenapine versus placebo on Day 7 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
1.8 to 7.3
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Analysis is for asenapine versus placebo on Day 14 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
1.1 to 4.1
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Analysis is for asenapine versus placebo on Day 14 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
2.2 to 7.6
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Analysis is for asenapine versus placebo on Day 14 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.1
Confidence Interval (2-Sided) 95%
2.2 to 7.6
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Analysis is for asenapine versus placebo on Day 21 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.042
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
1.0 to 3.4
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Analysis is for asenapine versus placebo on Day 21 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
1.7 to 5.8
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Analysis is for asenapine versus placebo on Day 21 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments 95% Confidence Interval and p-value are based on Wald statistic
Method Regression, Logistic
Comments Model included terms of treatment and baseline Y-MRS total score
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.9
Confidence Interval 95%
1.6 to 5.3
Estimation Comments OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response.
4.Secondary Outcome
Title Change From Baseline in CGI-BP Mania Score at Day 4
Time Frame Baseline and Day 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 4 value of CGI-BP mania score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 93 97 93 90
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.3  (0.6) -0.6  (0.8) -0.5  (0.7) -0.5  (0.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.45 to -0.05
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.107
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.37 to 0.04
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.42 to -0.01
Estimation Comments Estimate is asenapine versus placebo
5.Secondary Outcome
Title Change From Baseline in CGI-BP Mania Score at Day 7
Time Frame Baseline and Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CGI-BP mania score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 95 98 95 97
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.5  (0.7) -0.9  (0.9) -0.9  (1.0) -0.9  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.56 to -0.10
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.59 to -0.12
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-0.67 to -0.21
Estimation Comments Estimate is asenapine versus placebo
6.Secondary Outcome
Title Change From Baseline in CGI-BP Mania Score at Day 14
Time Frame Baseline and Day 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CGI-BP mania score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 89 91 90 91
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.6  (1.0) -1.1  (1.0) -1.4  (1.0) -1.3  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.61 to -0.08
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-0.89 to -0.36
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.61
Confidence Interval (2-Sided) 95%
-0.88 to -0.35
Estimation Comments Estimate is asenapine versus placebo
7.Secondary Outcome
Title Change From Baseline in CGI-BP Mania Score at Day 21
Time Frame Baseline and Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP mania score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 79 88 87 81
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.7  (0.9) -1.3  (1.1) -1.5  (1.1) -1.4  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.61
Confidence Interval (2-Sided) 95%
-0.90 to -0.32
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.75
Confidence Interval (2-Sided) 95%
-1.04 to -0.46
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-1.03 to -0.45
Estimation Comments Estimate is asenapine versus placebo
8.Secondary Outcome
Title Change From Baseline in CGI-BP Depression Score at Day 4
Time Frame Baseline and Day 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 4 value of CGI-BP depression score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 92 97 93 90
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.2  (0.7) -0.3  (0.8) -0.2  (1.0) -0.1  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.536
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.28 to 0.15
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.811
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.24 to 0.19
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.556
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.15 to 0.28
Estimation Comments Estimate is asenapine versus placebo
9.Secondary Outcome
Title Change From Baseline in CGI-BP Depression Score at Day 7
Time Frame Baseline and Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CGI-BP depression score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 94 98 95 97
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.4  (0.9) -0.5  (0.8) -0.5  (1.1) -0.5  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.053
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.42 to 0.00
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.094
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.40 to 0.03
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.178
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.36 to 0.07
Estimation Comments Estimate is asenapine versus placebo
10.Secondary Outcome
Title Change From Baseline in CGI-BP Depression Score at Day 14
Time Frame Baseline and Day 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CGI-BP depression score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 88 91 90 91
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.5  (1.1) -0.5  (1.0) -0.7  (1.0) -0.6  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.506
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.33 to 0.16
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.131
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.43 to 0.06
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.211
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.40 to 0.09
Estimation Comments Estimate is asenapine versus placebo
11.Secondary Outcome
Title Change From Baseline in CGI-BP Depression Score at Day 21
Time Frame Baseline and Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP depression score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 78 88 87 81
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.4  (1.0) -0.6  (1.1) -0.8  (1.1) -0.6  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.49 to 0.03
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.60 to -0.08
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.46 to 0.06
Estimation Comments Estimate is asenapine versus placebo
12.Secondary Outcome
Title Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score at Day 7
Hide Description The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values.
Time Frame Baseline and Day 7
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CDRS-R total score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 94 95 91 95
Mean (Standard Deviation)
Unit of Measure: score on a scale
-4.1  (8.1) -6.1  (7.1) -6.1  (8.0) -5.9  (8.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -2.61
Confidence Interval (2-Sided) 95%
-4.38 to -0.83
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -2.17
Confidence Interval (2-Sided) 95%
-3.95 to -0.39
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -2.16
Confidence Interval (2-Sided) 95%
-3.93 to -0.38
Estimation Comments Estimate is asenapine versus placebo
13.Secondary Outcome
Title Change From Baseline in CDRS-R Total Score at Day 14
Hide Description The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values.
Time Frame Baseline and Day 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CDRS-R total score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 88 89 90 90
Mean (Standard Deviation)
Unit of Measure: score on a scale
-5.5  (8.1) -5.8  (6.5) -8.7  (10.5) -6.6  (8.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.395
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -0.79
Confidence Interval (2-Sided) 95%
-2.62 to 1.04
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -2.44
Confidence Interval (2-Sided) 95%
-4.26 to -0.63
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-3.27 to 0.38
Estimation Comments Estimate is asenapine versus placebo
14.Secondary Outcome
Title Change From Baseline in CDRS-R Total Score at Day 21
Hide Description The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
Time Frame Baseline and Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CDRS-R total score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 78 87 87 81
Mean (Standard Deviation)
Unit of Measure: score on a scale
-6.1  (8.8) -6.9  (7.3) -8.7  (11.4) -6.8  (8.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.135
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -1.44
Confidence Interval (2-Sided) 95%
-3.33 to 0.45
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -2.19
Confidence Interval (2-Sided) 95%
-4.08 to -0.30
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments Model uses efficacy FAS population (number of participants: placebo – 98, asenapine 2.5 mg – 101, asenapine 5.0 mg – 98, asenapine 10.0 mg – 98)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.189
Comments [Not Specified]
Method MMRM
Comments Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -1.28
Confidence Interval (2-Sided) 95%
-3.20 to 0.63
Estimation Comments Estimate is asenapine versus placebo
15.Secondary Outcome
Title Change From Baseline in Children’s Global Assessment Scale (CGAS) Score at Day 21
Hide Description CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The reported measure is the change from baseline at Day 21; improvement in functioning is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.
Time Frame Baseline and Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of CGAS score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 84 93 91 85
Mean (Standard Deviation)
Unit of Measure: score on a scale
6.0  (8.1) 9.4  (9.5) 13.0  (11.6) 10.8  (9.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 4.29
Confidence Interval (2-Sided) 95%
1.56 to 7.02
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 6.95
Confidence Interval (2-Sided) 95%
4.22 to 9.68
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 5.11
Confidence Interval (2-Sided) 95%
2.31 to 7.91
Estimation Comments Estimate is asenapine versus placebo
16.Secondary Outcome
Title Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 21
Hide Description PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant was calculated as the sum of the rating assigned to each of the first 14 items, and ranged from 14 to 70 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.
Time Frame Baseline and Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of PQ-LES-Q total score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 84 92 90 84
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.5  (8.2) 3.7  (8.6) 2.5  (10.8) 4.0  (9.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 2.24
Confidence Interval (2-Sided) 95%
-0.00 to 4.48
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.239
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
-0.90 to 3.59
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 2.78
Confidence Interval (2-Sided) 95%
0.48 to 5.08
Estimation Comments Estimate is asenapine versus placebo
17.Secondary Outcome
Title Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 21
Hide Description PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The Item 15 result is defined to be the PQ-LES-Q overall score, and ranged from 1 to 5 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used.
Time Frame Baseline and Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of PQ-LES-Q overall score must be available for a participant.
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description:
Participants receive placebo BID for 21 days.
Participants receive asenapine 2.5 mg BID for 21 days.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
Overall Number of Participants Analyzed 84 92 90 84
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.0  (0.9) 0.4  (1.0) 0.1  (1.0) 0.2  (1.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 2.5 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.15 to 0.62
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 5.0 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.135
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-0.06 to 0.41
Estimation Comments Estimate is asenapine versus placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Asenapine 10.0 mg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments [Not Specified]
Method ANCOVA
Comments Model included terms of (pooled) site, treatment and baseline
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.01 to 0.49
Estimation Comments Estimate is asenapine versus placebo
Time Frame Up to 30 days after the last dose of study drug (Up to 51 days)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Hide Arm/Group Description Participants receive placebo BID for 21 days. Participants receive asenapine 2.5 mg BID for 21 days. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period. Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
All-Cause Mortality
Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/101 (2.97%)      0/104 (0.00%)      2/99 (2.02%)      2/99 (2.02%)    
Psychiatric disorders         
BIPOLAR DISORDER  1  1/101 (0.99%)  1 0/104 (0.00%)  0 0/99 (0.00%)  0 1/99 (1.01%)  1
BIPOLAR I DISORDER  1  1/101 (0.99%)  1 0/104 (0.00%)  0 1/99 (1.01%)  1 0/99 (0.00%)  0
MANIA  1  0/101 (0.00%)  0 0/104 (0.00%)  0 1/99 (1.01%)  1 0/99 (0.00%)  0
SUICIDAL BEHAVIOUR  1  1/101 (0.99%)  1 0/104 (0.00%)  0 0/99 (0.00%)  0 0/99 (0.00%)  0
SUICIDAL IDEATION  1  1/101 (0.99%)  1 0/104 (0.00%)  0 0/99 (0.00%)  0 0/99 (0.00%)  0
SUICIDE ATTEMPT  1  0/101 (0.00%)  0 0/104 (0.00%)  0 0/99 (0.00%)  0 1/99 (1.01%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Asenapine 2.5 mg BID Asenapine 5.0 mg BID Asenapine 10.0 mg BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/101 (29.70%)      68/104 (65.38%)      70/99 (70.71%)      72/99 (72.73%)    
Gastrointestinal disorders         
ABDOMINAL PAIN UPPER  1  6/101 (5.94%)  6 5/104 (4.81%)  5 2/99 (2.02%)  2 3/99 (3.03%)  3
HYPOAESTHESIA ORAL  1  2/101 (1.98%)  2 18/104 (17.31%)  18 18/99 (18.18%)  19 20/99 (20.20%)  21
NAUSEA  1  3/101 (2.97%)  3 6/104 (5.77%)  6 6/99 (6.06%)  6 6/99 (6.06%)  7
PARAESTHESIA ORAL  1  2/101 (1.98%)  2 9/104 (8.65%)  9 9/99 (9.09%)  9 11/99 (11.11%)  11
General disorders         
FATIGUE  1  5/101 (4.95%)  5 4/104 (3.85%)  4 8/99 (8.08%)  8 13/99 (13.13%)  13
Investigations         
WEIGHT INCREASED  1  0/101 (0.00%)  0 6/104 (5.77%)  6 2/99 (2.02%)  2 2/99 (2.02%)  2
Metabolism and nutrition disorders         
INCREASED APPETITE  1  2/101 (1.98%)  2 10/104 (9.62%)  10 9/99 (9.09%)  10 6/99 (6.06%)  6
Nervous system disorders         
DIZZINESS  1  3/101 (2.97%)  4 6/104 (5.77%)  6 10/99 (10.10%)  11 5/99 (5.05%)  5
DYSGEUSIA  1  2/101 (1.98%)  2 4/104 (3.85%)  4 5/99 (5.05%)  5 9/99 (9.09%)  9
HEADACHE  1  6/101 (5.94%)  6 8/104 (7.69%)  11 11/99 (11.11%)  12 9/99 (9.09%)  10
SEDATION  1  5/101 (4.95%)  5 16/104 (15.38%)  16 19/99 (19.19%)  19 18/99 (18.18%)  20
SOMNOLENCE  1  6/101 (5.94%)  6 34/104 (32.69%)  39 34/99 (34.34%)  36 31/99 (31.31%)  34
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01244815     History of Changes
Other Study ID Numbers: P06107
First Submitted: November 18, 2010
First Posted: November 19, 2010
Results First Submitted: August 21, 2014
Results First Posted: September 4, 2014
Last Update Posted: October 16, 2018