Bipolar 1 Disorder
Conditions
Brief summary
This trial will study the efficacy and safety of a fixed dose of asenapine in participants diagnosed with Bipolar 1 Disorder. Participants who qualify for the study will be randomly assigned to receive a fixed dose of asenapine (either 5 mg or 10 mg twice daily \[BID\]) or placebo (BID) for 3 weeks. Throughout the trial, observations will be made on each participant at various times to assess the safety and effectiveness of the study treatment. The primary hypothesis is that there is at least one dose of asenapine that is superior to placebo in the change from baseline in manic symptoms (as measured by Young Mania Rating Scale \[YMRS\]) at Day 21 of the trial.
Interventions
DRUGAsenapine
asenapine tablet, 5 mg sublingually BID for 21 days
DRUGPlacebo
placebo sublingual tablet, administered BID for 21 days
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Each participant must be at least 18 years of age * Male, or a female who is not of child-bearing potential or who is non-pregnant, non-lactating, and is using a medically accepted method of contraception * Each participant must have a current diagnosis of Bipolar I Disorder, current episode manic or mixed * Each participant must be confirmed to be experiencing an acute manic or mixed bipolar 1 episode * Each participant must have discontinued the use of all prohibited psychotropic medications
Exclusion criteria
* A participant must not have a primary Axis I disorder other than Bipolar 1 Disorder (i.e., an Axis 1 disorder other than Bipolar 1 Disorder that is primarily responsible for current symptoms and functional impairment) * A participant must not currently (within the past 6 months) meet the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR™) criteria for substance abuse or dependence (excluding nicotine) * A participant must not be at imminent risk of self-harm or harm to others, in the investigator's opinion based on clinical interview and responses provided on the Columbia Suicide Severity Rating Scale (CSSRS).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21 | Baseline and Day 21 | Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a mixed model repeated measures (MMRM) model. An improvement in symptoms is represented by change from baseline values that are negative. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Are Y-MRS Responders at Day 21 | Day 21 | Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by Last Observation Carried Forward (LOCF). Y-MRS responders are defined as having a \>= 50% decrease from baseline in Y-MRS total score. |
| Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Baseline and Day 2, Day 4, Day 7 and Day 14 | Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 2, Day 4, Day 7, Day 14 | Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS responders are defined as having a \>= 50% decrease from baseline in Y-MRS total score. |
| Percentage of Participants Who Are Y-MRS Remitters at Day 21 | Day 21 | Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower. |
| Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 2, Day 4, Day 7, Day 14, Day 21 | Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a generalized linear mixed model (GLMM). Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower. |
| Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Baseline and Day 7 and Day 21 | The MADRS measures depression and consists of 10 items, each rated on a scale from 0 to 6. The MADRS total score sums the scores from the 10 items, ranging from 0 to 60, with a higher numeric rating implying a greater degree of symptom severity. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Baseline and Day 2, Day 4, Day 7, Day 14 | The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in CGI-BP-S Mania Score | Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21 | The CGI-BP-S mania is a score that assesses the severity of the mania component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in CGI-BP-S Depression Score | Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21 | The CGI-BP-S depression is a score that assesses the severity of the depression component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative. |
| Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 2, Day 4, Day 7, Day 14, and Day 21 | The CGI-BP-I overall is a score on a 7-point scale for assessing the change from preceding phase of overall symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I overall score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower. |
| Change From Baseline in Clinical Global Impression - Bipolar Mania - Severity of Illness (CGI-BP-S) Overall Score at Day 21 | Baseline and Day 21 | The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 2, Day 4, Day 7, Day 14, and Day 21 | The CGI-BP-I depression is a score on a 7-point scale for assessing the change from preceding phase of depression symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I depression score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower. |
| Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Baseline and Day 7, Day 14, Day 21 | PANSS total score measures symptoms of schizophrenia and consists of responses to 30 items: 7 items from the positive subscale (P1-P7), 7 items from the negative subscale (N1-N7) and 16 items from the general psychopathology subscale (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS total score sums the scores from all 30 items, and ranges from 30 to 210, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in PANSS Negative Subscale Score | Baseline and Day 7, Day 14, Day 21 | PANSS Negative subscale measures symptoms of schizophrenia and consists of responses to 7 items (N1-N7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Negative subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in PANSS Positive Subscale Score | Baseline and Day 7, Day 14, Day 21 | PANSS Positive subscale measures symptoms of schizophrenia and consists of responses to 7 items (P1-P7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Positive subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in PANSS General Psychopathology Subscale Score | Baseline and Day 7, Day 14, Day 21 | PANSS General Psychopathology subscale measures symptoms of schizophrenia and consists of responses to 16 items (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS General Psychopathology subscale sums the scores from all 16 items and ranges from 16 to 112, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in PANSS Marder Factor Positive Symptom Score | Baseline and Day 7, Day 14, Day 21 | PANSS Marder Factor Positive symptom score measures symptoms of schizophrenia and consists of responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Positive symptom score sums the scores from all 8 items and ranges from 8 to 56, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in PANSS Marder Factor Negative Symptom Score | Baseline and Day 7, Day 14, Day 21 | PANSS Marder Factor Negative symptom score measures symptoms of schizophrenia and consists of responses to 7 items (N1,N2,N3,N4,N6,G7,G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Negative symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Baseline and Day 7, Day 14, Day 21 | PANSS Marder Factor Disorganized Thought symptom score measures symptoms of schizophrenia and consists of responses to 7 items (P2,N5,G5,G10,G11,G13,G15). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Disorganized Thought symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Baseline and Day 7, Day 14, Day 21 | PANSS Marder Factor Hostility/Excitement symptom score measures symptoms of schizophrenia and consists of responses to 4 items (P4,P7,G8,G14). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Hostility/Excitement symptom score sums the score from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Baseline and Day 7, Day14, Day 21 | PANSS Marder Factor Anxiety/Depression symptom score measures symptoms of schizophrenia and consists of responses to 4 items (G2,G3,G4,G6). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Anxiety/Depression symptom score sums the scores from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative. |
| Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 2, Day 4, Day 7, Day 14, and Day 21 | The CGI-BP-I mania is a score on a 7-point scale for assessing the change from preceding phase of mania symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I mania score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asenapine 5 mg BID Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days | 122 |
| Asenapine 10 mg BID Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days | 119 |
| Placebo BID Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days | 126 |
| Total | 367 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 7 | 8 | 5 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 12 | 1 |
Baseline characteristics
| Characteristic | Asenapine 5 mg BID | Asenapine 10 mg BID | Placebo BID | Total |
|---|---|---|---|---|
| Age, Continuous | 44.3 Years STANDARD_DEVIATION 10.82 | 42.5 Years STANDARD_DEVIATION 11.06 | 44.6 Years STANDARD_DEVIATION 11.54 | 43.8 Years STANDARD_DEVIATION 11.16 |
| Sex: Female, Male Female | 65 Participants | 64 Participants | 72 Participants | 201 Participants |
| Sex: Female, Male Male | 57 Participants | 55 Participants | 54 Participants | 166 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 43 / 122 | 67 / 119 | 24 / 126 |
| serious Total, serious adverse events | 3 / 122 | 1 / 119 | 2 / 126 |
Outcome results
Primary
Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21
Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a mixed model repeated measures (MMRM) model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21 | -14.4 Score on a scale | Standard Error 1.02 |
| Asenapine 10 mg BID | Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21 | -14.9 Score on a scale | Standard Error 1.04 |
| Placebo BID | Change From Baseline in Young Mania Rating Scale (Y-MRS) Total Score at Day 21 | -10.9 Score on a scale | Standard Error 0.99 |
p-value: 0.013695% CI: [-6.3, -0.7]MMRM
p-value: 0.0195% CI: [-6.9, -1.2]MMRM
Secondary
Change From Baseline in CGI-BP-S Depression Score
The CGI-BP-S depression is a score that assesses the severity of the depression component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 14 (n=120,113,125) | -0.4 Score on a scale | Standard Error 0.07 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 7 (n=120,113,125) | -0.3 Score on a scale | Standard Error 0.07 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 2 (n=118,111,122) | -0.2 Score on a scale | Standard Error 0.06 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 4 (n=120,113,125) | -0.3 Score on a scale | Standard Error 0.06 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 21 (n=120,113,125) | -0.4 Score on a scale | Standard Error 0.08 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 7 (n=120,113,125) | -0.4 Score on a scale | Standard Error 0.07 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 2 (n=118,111,122) | -0.2 Score on a scale | Standard Error 0.06 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 4 (n=120,113,125) | -0.3 Score on a scale | Standard Error 0.06 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 14 (n=120,113,125) | -0.5 Score on a scale | Standard Error 0.07 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Depression Score | Day 21 (n=120,113,125) | -0.5 Score on a scale | Standard Error 0.08 |
| Placebo BID | Change From Baseline in CGI-BP-S Depression Score | Day 21 (n=120,113,125) | -0.1 Score on a scale | Standard Error 0.08 |
| Placebo BID | Change From Baseline in CGI-BP-S Depression Score | Day 14 (n=120,113,125) | -0.2 Score on a scale | Standard Error 0.07 |
| Placebo BID | Change From Baseline in CGI-BP-S Depression Score | Day 2 (n=118,111,122) | -0.2 Score on a scale | Standard Error 0.06 |
| Placebo BID | Change From Baseline in CGI-BP-S Depression Score | Day 7 (n=120,113,125) | -0.1 Score on a scale | Standard Error 0.07 |
| Placebo BID | Change From Baseline in CGI-BP-S Depression Score | Day 4 (n=120,113,125) | -0.3 Score on a scale | Standard Error 0.06 |
Comparison: Day 2p-value: 0.9708ANCOVA
Comparison: Day 2p-value: 0.7891ANCOVA
Comparison: Day 4p-value: 0.5222ANCOVA
Comparison: Day 4p-value: 0.8686ANCOVA
Comparison: Day 7p-value: 0.0696ANCOVA
Comparison: Day 7p-value: 0.0049ANCOVA
Comparison: Day 14p-value: 0.0196ANCOVA
Comparison: Day 14p-value: 0.0032ANCOVA
Comparison: Day 21p-value: 0.0061ANCOVA
Comparison: Day 21p-value: 0.0012ANCOVA
Secondary
Change From Baseline in CGI-BP-S Mania Score
The CGI-BP-S mania is a score that assesses the severity of the mania component of bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement, and had evaluable post-baseline measurement at timepoint. One participant from the Placebo BID arm missed a baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 14 (n=120,113,125) | -1.2 Score on a scale | Standard Error 0.1 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 7 (n=120,113,125) | -0.9 Score on a scale | Standard Error 0.09 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 2 (n=118,111,122) | -0.4 Score on a scale | Standard Error 0.06 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 4 (n=120,113,125) | -0.7 Score on a scale | Standard Error 0.07 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 21 (n=120,113,125) | -1.4 Score on a scale | Standard Error 0.11 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 7 (n=120,113,125) | -1.0 Score on a scale | Standard Error 0.09 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 2 (n=118,111,122) | -0.4 Score on a scale | Standard Error 0.06 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 4 (n=120,113,125) | -0.7 Score on a scale | Standard Error 0.08 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 14 (n=120,113,125) | -1.3 Score on a scale | Standard Error 0.11 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Mania Score | Day 21 (n=120,113,125) | -1.5 Score on a scale | Standard Error 0.12 |
| Placebo BID | Change From Baseline in CGI-BP-S Mania Score | Day 21 (n=120,113,125) | -1.1 Score on a scale | Standard Error 0.11 |
| Placebo BID | Change From Baseline in CGI-BP-S Mania Score | Day 14 (n=120,113,125) | -1.0 Score on a scale | Standard Error 0.1 |
| Placebo BID | Change From Baseline in CGI-BP-S Mania Score | Day 2 (n=118,111,122) | -0.1 Score on a scale | Standard Error 0.06 |
| Placebo BID | Change From Baseline in CGI-BP-S Mania Score | Day 7 (n=120,113,125) | -0.7 Score on a scale | Standard Error 0.09 |
| Placebo BID | Change From Baseline in CGI-BP-S Mania Score | Day 4 (n=120,113,125) | -0.3 Score on a scale | Standard Error 0.07 |
Comparison: Day 2p-value: 0.0005ANCOVA
Comparison: Day 2p-value: 0.0026ANCOVA
Comparison: Day 4p-value: 0.0007ANCOVA
Comparison: Day 4p-value: 0.0002ANCOVA
Comparison: Day 7p-value: 0.0387ANCOVA
Comparison: Day 7p-value: 0.0059ANCOVA
Comparison: Day 14p-value: 0.311ANCOVA
Comparison: Day 14p-value: 0.0613ANCOVA
Comparison: Day 21p-value: 0.064ANCOVA
Comparison: Day 21p-value: 0.0139ANCOVA
Secondary
Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14
The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 2, Day 4, Day 7, Day 14
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. One participant from the Placebo BID arm missed a baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 2 | -0.5 Score on a scale | Standard Error 0.05 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 4 | -0.8 Score on a scale | Standard Error 0.07 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 7 | -1.0 Score on a scale | Standard Error 0.09 |
| Asenapine 5 mg BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 14 | -1.3 Score on a scale | Standard Error 0.1 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 14 | -1.3 Score on a scale | Standard Error 0.11 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 2 | -0.4 Score on a scale | Standard Error 0.06 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 7 | -1.1 Score on a scale | Standard Error 0.09 |
| Asenapine 10 mg BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 4 | -0.7 Score on a scale | Standard Error 0.07 |
| Placebo BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 14 | -1.0 Score on a scale | Standard Error 0.1 |
| Placebo BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 4 | -0.4 Score on a scale | Standard Error 0.07 |
| Placebo BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 7 | -0.7 Score on a scale | Standard Error 0.09 |
| Placebo BID | Change From Baseline in CGI-BP-S Overall Score at Day 2, Day 4, Day 7, Day 14 | Day 2 | -0.2 Score on a scale | Standard Error 0.05 |
Comparison: Day 2p-value: <0.000195% CI: [-0.4, -0.1]MMRM
Comparison: Day 2p-value: 0.007695% CI: [-0.3, -0.1]MMRM
Comparison: Day 4p-value: 0.000495% CI: [-0.6, -0.2]MMRM
Comparison: Day 4p-value: 0.00495% CI: [-0.5, -0.1]MMRM
Comparison: Day 7p-value: 0.006195% CI: [-0.6, -0.1]MMRM
Comparison: Day 7p-value: 0.003195% CI: [-0.6, -0.1]MMRM
Comparison: Day 14p-value: 0.108695% CI: [-0.5, 0.1]MMRM
Comparison: Day 14p-value: 0.037695% CI: [-0.6, 0]MMRM
Secondary
Change From Baseline in Clinical Global Impression - Bipolar Mania - Severity of Illness (CGI-BP-S) Overall Score at Day 21
The CGI-BP-S is a score that measures the severity of overall bipolar illness. The score ranges on a scale from 1 to 7, where 1 is normal, and 7 is very severely ill. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. One participant from the Placebo BID arm missed a baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in Clinical Global Impression - Bipolar Mania - Severity of Illness (CGI-BP-S) Overall Score at Day 21 | -1.6 Score on a scale | Standard Error 0.12 |
| Asenapine 10 mg BID | Change From Baseline in Clinical Global Impression - Bipolar Mania - Severity of Illness (CGI-BP-S) Overall Score at Day 21 | -1.7 Score on a scale | Standard Error 0.12 |
| Placebo BID | Change From Baseline in Clinical Global Impression - Bipolar Mania - Severity of Illness (CGI-BP-S) Overall Score at Day 21 | -1.1 Score on a scale | Standard Error 0.11 |
p-value: 0.005295% CI: [-0.9, -0.2]MMRM
p-value: 0.0195% CI: [-0.8, -0.2]MMRM
Secondary
Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
The MADRS measures depression and consists of 10 items, each rated on a scale from 0 to 6. The MADRS total score sums the scores from the 10 items, ranging from 0 to 60, with a higher numeric rating implying a greater degree of symptom severity. Missing data were imputed by LOCF. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7 and Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Day 7 (n=112,106, 117) | -4.3 Score on a scale | Standard Error 0.47 |
| Asenapine 5 mg BID | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Day 21 (n =115, 110,123) | -4.6 Score on a scale | Standard Error 0.61 |
| Asenapine 10 mg BID | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Day 7 (n=112,106, 117) | -4.2 Score on a scale | Standard Error 0.48 |
| Asenapine 10 mg BID | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Day 21 (n =115, 110,123) | -5.1 Score on a scale | Standard Error 0.63 |
| Placebo BID | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Day 7 (n=112,106, 117) | -2.3 Score on a scale | Standard Error 0.46 |
| Placebo BID | Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | Day 21 (n =115, 110,123) | -2.5 Score on a scale | Standard Error 0.6 |
Comparison: Day 7p-value: 0.0019ANCOVA
Comparison: Day 7p-value: 0.0045ANCOVA
Comparison: Day 21p-value: 0.0112ANCOVA
Comparison: Day 21p-value: 0.0021ANCOVA
Secondary
Change From Baseline in PANSS General Psychopathology Subscale Score
PANSS General Psychopathology subscale measures symptoms of schizophrenia and consists of responses to 16 items (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS General Psychopathology subscale sums the scores from all 16 items and ranges from 16 to 112, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 14 | -4.5 Score on a scale | Standard Error 0.57 |
| Asenapine 5 mg BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 7 | -4.0 Score on a scale | Standard Error 0.46 |
| Asenapine 5 mg BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 21 | -5.5 Score on a scale | Standard Error 0.61 |
| Asenapine 10 mg BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 14 | -4.6 Score on a scale | Standard Error 0.59 |
| Asenapine 10 mg BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 7 | -3.3 Score on a scale | Standard Error 0.48 |
| Asenapine 10 mg BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 21 | -4.9 Score on a scale | Standard Error 0.62 |
| Placebo BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 7 | -2.1 Score on a scale | Standard Error 0.46 |
| Placebo BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 21 | -2.9 Score on a scale | Standard Error 0.59 |
| Placebo BID | Change From Baseline in PANSS General Psychopathology Subscale Score | Day 14 | -2.4 Score on a scale | Standard Error 0.56 |
Comparison: Day 7p-value: 0.003395% CI: [-3.2, -0.6]MMRM
Comparison: Day 7p-value: 0.062295% CI: [-2.5, 0.1]MMRM
Comparison: Day 14p-value: 0.008395% CI: [-3.6, -0.5]MMRM
Comparison: Day 14p-value: 0.006495% CI: [-3.8, -0.6]MMRM
Comparison: Day 21p-value: 0.002295% CI: [-4.3, -0.9]MMRM
Comparison: Day 21p-value: 0.019695% CI: [-3.7, -0.3]MMRM
Secondary
Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score
PANSS Marder Factor Anxiety/Depression symptom score measures symptoms of schizophrenia and consists of responses to 4 items (G2,G3,G4,G6). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Anxiety/Depression symptom score sums the scores from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 14 | -2.0 Score on a scale | Standard Error 0.26 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 7 | -1.7 Score on a scale | Standard Error 0.24 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 21 | -2.1 Score on a scale | Standard Error 0.3 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 14 | -1.7 Score on a scale | Standard Error 0.27 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 7 | -1.3 Score on a scale | Standard Error 0.24 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 21 | -1.9 Score on a scale | Standard Error 0.3 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 7 | -0.7 Score on a scale | Standard Error 0.23 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 21 | -1.0 Score on a scale | Standard Error 0.29 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Anxiety/Depression Symptom Score | Day 14 | -0.7 Score on a scale | Standard Error 0.26 |
Comparison: Day 7p-value: 0.001995% CI: [-1.7, -0.4]MMRM
Comparison: Day 7p-value: 0.079195% CI: [-1.2, 0.1]MMRM
Comparison: Day 14p-value: 0.000695% CI: [-2, -0.5]MMRM
Comparison: Day 14p-value: 0.012395% CI: [-1.6, -0.2]MMRM
Comparison: Day 21p-value: 0.005495% CI: [-2, -0.3]MMRM
Comparison: Day 21p-value: 0.03595% CI: [-1.7, -0.1]MMRM
Secondary
Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score
PANSS Marder Factor Disorganized Thought symptom score measures symptoms of schizophrenia and consists of responses to 7 items (P2,N5,G5,G10,G11,G13,G15). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Disorganized Thought symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 14 | -1.5 Score on a scale | Standard Error 0.26 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 7 | -1.1 Score on a scale | Standard Error 0.21 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 21 | -2.0 Score on a scale | Standard Error 0.28 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 14 | -1.8 Score on a scale | Standard Error 0.27 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 7 | -1.3 Score on a scale | Standard Error 0.22 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 21 | -1.7 Score on a scale | Standard Error 0.29 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 7 | -0.7 Score on a scale | Standard Error 0.21 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 21 | -1.5 Score on a scale | Standard Error 0.27 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Disorganized Thought Symptom Score | Day 14 | -1.2 Score on a scale | Standard Error 0.26 |
Comparison: Day 7p-value: 0.219195% CI: [-0.9, 0.2]MMRM
Comparison: Day 7p-value: 0.058995% CI: [-1.1, 0]MMRM
Comparison: Day 14p-value: 0.368395% CI: [-1, 0.4]MMRM
Comparison: Day 14p-value: 0.098295% CI: [-1.3, 0.1]MMRM
Comparison: Day 21p-value: 0.196995% CI: [-1.3, 0.3]MMRM
Comparison: Day 21p-value: 0.561595% CI: [-1, 0.5]MMRM
Secondary
Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score
PANSS Marder Factor Hostility/Excitement symptom score measures symptoms of schizophrenia and consists of responses to 4 items (P4,P7,G8,G14). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Hostility/Excitement symptom score sums the score from all 4 items and ranges from 4 to 28, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 14 | -1.8 Score on a scale | Standard Error 0.28 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 7 | -1.7 Score on a scale | Standard Error 0.24 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 21 | -2.6 Score on a scale | Standard Error 0.29 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 14 | -2.0 Score on a scale | Standard Error 0.29 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 7 | -1.7 Score on a scale | Standard Error 0.25 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 21 | -2.5 Score on a scale | Standard Error 0.3 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 7 | -0.9 Score on a scale | Standard Error 0.24 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 21 | -1.5 Score on a scale | Standard Error 0.28 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Hostility/Excitement Symptom Score | Day 14 | -1.2 Score on a scale | Standard Error 0.27 |
Comparison: Day 7p-value: 0.010195% CI: [-1.5, -0.2]MMRM
Comparison: Day 7p-value: 0.014695% CI: [-1.5, -0.2]MMRM
Comparison: Day 14p-value: 0.086195% CI: [-1.4, 0.1]MMRM
Comparison: Day 14p-value: 0.034295% CI: [-1.6, -0.1]MMRM
Comparison: Day 21p-value: 0.003795% CI: [-2, -0.4]MMRM
Comparison: Day 21p-value: 0.009695% CI: [-1.9, -0.3]MMRM
Secondary
Change From Baseline in PANSS Marder Factor Negative Symptom Score
PANSS Marder Factor Negative symptom score measures symptoms of schizophrenia and consists of responses to 7 items (N1,N2,N3,N4,N6,G7,G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Negative symptom score sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 14 | -0.6 Score on a scale | Standard Error 0.24 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 7 | -0.5 Score on a scale | Standard Error 0.23 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 21 | -0.1 Score on a scale | Standard Error 0.27 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 14 | -0.5 Score on a scale | Standard Error 0.25 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 7 | -0.8 Score on a scale | Standard Error 0.24 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 21 | 0.1 Score on a scale | Standard Error 0.28 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 7 | -0.5 Score on a scale | Standard Error 0.23 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 21 | -0.1 Score on a scale | Standard Error 0.27 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Negative Symptom Score | Day 14 | -0.7 Score on a scale | Standard Error 0.24 |
Comparison: Day 7p-value: 0.774695% CI: [-0.7, 0.5]MMRM
Comparison: Day 7p-value: 0.275495% CI: [-1, 0.3]MMRM
Comparison: Day 14p-value: 0.910995% CI: [-0.6, 0.7]MMRM
Comparison: Day 14p-value: 0.729595% CI: [-0.6, 0.8]MMRM
Comparison: Day 21p-value: 0.9895% CI: [-0.7, 0.8]MMRM
Comparison: Day 21p-value: 0.512295% CI: [-0.5, 1]MMRM
Secondary
Change From Baseline in PANSS Marder Factor Positive Symptom Score
PANSS Marder Factor Positive symptom score measures symptoms of schizophrenia and consists of responses to 8 items (P1,P3,P5,P6,N7,G1,G9,G12). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Marder Factor Positive symptom score sums the scores from all 8 items and ranges from 8 to 56, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 14 | -1.6 Score on a scale | Standard Error 0.33 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 7 | -1.9 Score on a scale | Standard Error 0.29 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 21 | -2.6 Score on a scale | Standard Error 0.34 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 14 | -2.5 Score on a scale | Standard Error 0.34 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 7 | -1.9 Score on a scale | Standard Error 0.29 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 21 | -2.9 Score on a scale | Standard Error 0.35 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 7 | -1.3 Score on a scale | Standard Error 0.28 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 21 | -1.7 Score on a scale | Standard Error 0.33 |
| Placebo BID | Change From Baseline in PANSS Marder Factor Positive Symptom Score | Day 14 | -1.6 Score on a scale | Standard Error 0.33 |
Comparison: Day 7p-value: 0.188395% CI: [-1.3, 0.3]MMRM
Comparison: Day 7p-value: 0.168495% CI: [-1.3, 0.2]MMRM
Comparison: Day 14p-value: 0.952295% CI: [-0.9, 0.9]MMRM
Comparison: Day 14p-value: 0.051495% CI: [-1.8, 0]MMRM
Comparison: Day 21p-value: 0.053195% CI: [-1.8, 0]MMRM
Comparison: Day 21p-value: 0.007895% CI: [-2.2, -0.3]MMRM
Secondary
Change From Baseline in PANSS Negative Subscale Score
PANSS Negative subscale measures symptoms of schizophrenia and consists of responses to 7 items (N1-N7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Negative subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in PANSS Negative Subscale Score | Day 14 | -0.8 Score on a scale | Standard Error 0.23 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Negative Subscale Score | Day 7 | -0.5 Score on a scale | Standard Error 0.22 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Negative Subscale Score | Day 21 | -0.4 Score on a scale | Standard Error 0.28 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Negative Subscale Score | Day 14 | -0.7 Score on a scale | Standard Error 0.24 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Negative Subscale Score | Day 7 | -0.8 Score on a scale | Standard Error 0.22 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Negative Subscale Score | Day 21 | -0.0 Score on a scale | Standard Error 0.29 |
| Placebo BID | Change From Baseline in PANSS Negative Subscale Score | Day 7 | -0.5 Score on a scale | Standard Error 0.21 |
| Placebo BID | Change From Baseline in PANSS Negative Subscale Score | Day 21 | -0.4 Score on a scale | Standard Error 0.27 |
| Placebo BID | Change From Baseline in PANSS Negative Subscale Score | Day 14 | -0.8 Score on a scale | Standard Error 0.23 |
Comparison: Day 7p-value: 0.980895% CI: [-0.6, 0.6]MMRM
Comparison: Day 7p-value: 0.28395% CI: [-0.9, 0.3]MMRM
Comparison: Day 14p-value: 0.975195% CI: [-0.6, 0.6]MMRM
Comparison: Day 14p-value: 0.787995% CI: [-0.6, 0.7]MMRM
Comparison: Day 21p-value: 0.965495% CI: [-0.8, 0.7]MMRM
Comparison: Day 21p-value: 0.391795% CI: [-0.4, 1.1]MMRM
Secondary
Change From Baseline in PANSS Positive Subscale Score
PANSS Positive subscale measures symptoms of schizophrenia and consists of responses to 7 items (P1-P7). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS Positive subscale sums the scores from all 7 items and ranges from 7 to 49, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in PANSS Positive Subscale Score | Day 14 | -2.3 Score on a scale | Standard Error 0.37 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Positive Subscale Score | Day 7 | -2.4 Score on a scale | Standard Error 0.3 |
| Asenapine 5 mg BID | Change From Baseline in PANSS Positive Subscale Score | Day 21 | -3.5 Score on a scale | Standard Error 0.37 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Positive Subscale Score | Day 21 | -3.9 Score on a scale | Standard Error 0.38 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Positive Subscale Score | Day 7 | -2.8 Score on a scale | Standard Error 0.31 |
| Asenapine 10 mg BID | Change From Baseline in PANSS Positive Subscale Score | Day 14 | -3.2 Score on a scale | Standard Error 0.38 |
| Placebo BID | Change From Baseline in PANSS Positive Subscale Score | Day 14 | -2.1 Score on a scale | Standard Error 0.36 |
| Placebo BID | Change From Baseline in PANSS Positive Subscale Score | Day 21 | -2.4 Score on a scale | Standard Error 0.36 |
| Placebo BID | Change From Baseline in PANSS Positive Subscale Score | Day 7 | -1.4 Score on a scale | Standard Error 0.29 |
Comparison: Day 7p-value: 0.01295% CI: [-1.8, -0.2]MMRM
Comparison: Day 7p-value: 0.001195% CI: [-2.2, -0.5]MMRM
Comparison: Day 14p-value: 0.688595% CI: [-1.2, 0.8]MMRM
Comparison: Day 14p-value: 0.039895% CI: [-2.1, -0.1]MMRM
Comparison: Day 21p-value: 0.025895% CI: [-2.1, -0.1]MMRM
Comparison: Day 21p-value: 0.003195% CI: [-2.5, -0.5]MMRM
Secondary
Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score
PANSS total score measures symptoms of schizophrenia and consists of responses to 30 items: 7 items from the positive subscale (P1-P7), 7 items from the negative subscale (N1-N7) and 16 items from the general psychopathology subscale (G1-G16). Responses to each item range from 1 = absence of symptom, to 7 = most extreme symptoms. The PANSS total score sums the scores from all 30 items, and ranges from 30 to 210, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 14 | -7.5 Score on a scale | Standard Error 0.96 |
| Asenapine 5 mg BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 7 | -6.9 Score on a scale | Standard Error 0.77 |
| Asenapine 5 mg BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 21 | -9.3 Score on a scale | Standard Error 1.02 |
| Asenapine 10 mg BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 21 | -8.8 Score on a scale | Standard Error 1.05 |
| Asenapine 10 mg BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 7 | -6.9 Score on a scale | Standard Error 0.79 |
| Asenapine 10 mg BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 14 | -8.4 Score on a scale | Standard Error 0.99 |
| Placebo BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 14 | -5.2 Score on a scale | Standard Error 0.94 |
| Placebo BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 21 | -5.5 Score on a scale | Standard Error 1 |
| Placebo BID | Change From Baseline in Positive And Negative Syndrome Scale (PANSS) Total Score | Day 7 | -3.9 Score on a scale | Standard Error 0.76 |
Comparison: Day 7p-value: 0.005695% CI: [-5.1, -0.9]MMRM
Comparison: Day 7p-value: 0.006895% CI: [-5, -0.8]MMRM
Comparison: Day 14p-value: 0.074395% CI: [-5, 0.2]MMRM
Comparison: Day 14p-value: 0.017795% CI: [-5.9, -0.6]MMRM
Comparison: Day 21p-value: 0.008195% CI: [-6.6, -1]MMRM
Comparison: Day 21p-value: 0.024795% CI: [-6.1, -0.4]MMRM
Secondary
Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14
Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a MMRM model. An improvement in symptoms is represented by change from baseline values that are negative.
Time frame: Baseline and Day 2, Day 4, Day 7 and Day 14
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Asenapine 5 mg BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 2 | -5.6 Score on a scale | Standard Error 0.57 |
| Asenapine 5 mg BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 4 | -8.6 Score on a scale | Standard Error 0.67 |
| Asenapine 5 mg BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 7 | -10.0 Score on a scale | Standard Error 0.81 |
| Asenapine 5 mg BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 14 | -11.1 Score on a scale | Standard Error 0.98 |
| Asenapine 10 mg BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 14 | -12.5 Score on a scale | Standard Error 1 |
| Asenapine 10 mg BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 2 | -5.8 Score on a scale | Standard Error 0.59 |
| Asenapine 10 mg BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 7 | -10.7 Score on a scale | Standard Error 0.83 |
| Asenapine 10 mg BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 4 | -8.6 Score on a scale | Standard Error 0.68 |
| Placebo BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 14 | -9.4 Score on a scale | Standard Error 0.95 |
| Placebo BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 4 | -4.9 Score on a scale | Standard Error 0.64 |
| Placebo BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 7 | -6.6 Score on a scale | Standard Error 0.79 |
| Placebo BID | Change From Baseline in Y-MRS Total Score at Day 2, Day 4, Day 7 and Day 14 | Day 2 | -2.9 Score on a scale | Standard Error 0.56 |
Comparison: Day 2p-value: 0.000795% CI: [-4.2, -1.1]MMRM
Comparison: Day 2p-value: 0.000395% CI: [-4.4, -1.3]MMRM
Comparison: Day 4p-value: <0.000195% CI: [-5.4, -1.8]MMRM
Comparison: Day 4p-value: <0.000195% CI: [-5.5, -1.9]MMRM
Comparison: Day 7p-value: 0.002195% CI: [-5.7, -1.3]MMRM
Comparison: Day 7p-value: 0.000295% CI: [-6.4, -2]MMRM
Comparison: Day 14p-value: 0.190795% CI: [-4.4, 0.9]MMRM
Comparison: Day 14p-value: 0.023895% CI: [-5.8, -0.4]MMRM
Secondary
Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score
The CGI-BP-I depression is a score on a 7-point scale for assessing the change from preceding phase of depression symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I depression score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.
Time frame: Day 2, Day 4, Day 7, Day 14, and Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 14 (n=117, 106, 120) | 31.6 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 7 (n=117, 106, 119) | 31.6 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 2 (n=113, 103, 116) | 21.2 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 4 (n=116, 106, 119) | 26.7 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 21 (n=117, 106, 121) | 32.5 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 7 (n=117, 106, 119) | 35.8 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 2 (n=113, 103, 116) | 28.2 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 4 (n=116, 106, 119) | 32.1 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 14 (n=117, 106, 120) | 42.5 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 21 (n=117, 106, 121) | 44.3 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 21 (n=117, 106, 121) | 28.9 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 14 (n=117, 106, 120) | 26.7 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 2 (n=113, 103, 116) | 11.2 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 7 (n=117, 106, 119) | 23.5 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Depression Score | Day 4 (n=116, 106, 119) | 19.3 Percentage of participants |
Comparison: Day 2p-value: 0.0104Cochran-Mantel-Haenszel
Comparison: Day 2p-value: 0.0005Cochran-Mantel-Haenszel
Comparison: Day 4p-value: 0.0692Cochran-Mantel-Haenszel
Comparison: Day 4p-value: 0.0128Cochran-Mantel-Haenszel
Comparison: Day 7p-value: 0.0809Cochran-Mantel-Haenszel
Comparison: Day 7p-value: 0.026Cochran-Mantel-Haenszel
Comparison: Day 14p-value: 0.2576Cochran-Mantel-Haenszel
Comparison: Day 14p-value: 0.0077Cochran-Mantel-Haenszel
Comparison: Day 21p-value: 0.396Cochran-Mantel-Haenszel
Comparison: Day 21p-value: 0.0141Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score
The CGI-BP-I mania is a score on a 7-point scale for assessing the change from preceding phase of mania symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I mania score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.
Time frame: Day 2, Day 4, Day 7, Day 14, and Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 14 (n=120,113,126) | 75.8 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 7 (n=120,113,126) | 74.2 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 2 (n=118,111,123) | 49.2 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 4 (n=120,113,126) | 64.2 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 21 (n=120,113,126) | 79.2 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 7 (n=120,113,126) | 80.5 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 2 (n=118,111,123) | 45.9 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 4 (n=120,113,126) | 66.4 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 14 (n=120,113,126) | 82.3 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 21 (n=120,113,126) | 84.1 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 21 (n=120,113,126) | 66.7 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 14 (n=120,113,126) | 66.7 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 2 (n=118,111,123) | 37.4 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 7 (n=120,113,126) | 63.5 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Mania Score | Day 4 (n=120,113,126) | 55.6 Percentage of participants |
Comparison: Day 2p-value: 0.0377Cochran-Mantel-Haenszel
Comparison: Day 2p-value: 0.0771Cochran-Mantel-Haenszel
Comparison: Day 4p-value: 0.1264Cochran-Mantel-Haenszel
Comparison: Day 4p-value: 0.028Cochran-Mantel-Haenszel
Comparison: Day 7p-value: 0.0583Cochran-Mantel-Haenszel
Comparison: Day 7p-value: 0.0021Cochran-Mantel-Haenszel
Comparison: Day 14p-value: 0.0866Cochran-Mantel-Haenszel
Comparison: Day 14p-value: 0.0048Cochran-Mantel-Haenszel
Comparison: Day 21p-value: 0.0147Cochran-Mantel-Haenszel
Comparison: Day 21p-value: 0.003Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score
The CGI-BP-I overall is a score on a 7-point scale for assessing the change from preceding phase of overall symptoms of bipolar disorder during the treatment of an acute episode or in longer term illness prophylaxis. Compared to the baseline, the CGI-BP-I overall score ranges from 1 = very much improved since initiating treatment, to 7 = very much worse since initiating treatment. Missing data were imputed by LOCF. A CGI-BP-I responder had a score of 3 (minimally improved) or lower.
Time frame: Day 2, Day 4, Day 7, Day 14, and Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 14 (n=120,113,126) | 70.8 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 7 (n=120,113,126) | 73.3 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 2 (n=118,111,123) | 50.8 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 4 (n=120,113,126) | 64.2 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 21 (n=120,113,126) | 74.2 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 7 (n=120,113,126) | 78.8 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 2 (n=118,111,123) | 45.9 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 4 (n=120,113,126) | 64.6 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 14 (n=120,113,126) | 83.2 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 21 (n=120,113,126) | 82.3 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 21 (n=120,113,126) | 64.3 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 14 (n=120,113,126) | 65.1 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 2 (n=118,111,123) | 37.4 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 7 (n=120,113,126) | 61.1 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are CGI-BP Improvement (CGI-BP-I) Responders of Overall Bipolar Illness Score | Day 4 (n=120,113,126) | 55.6 Percentage of participants |
Comparison: Day 2p-value: 0.0147Cochran-Mantel-Haenszel
Comparison: Day 2p-value: 0.072Cochran-Mantel-Haenszel
Comparison: Day 4p-value: 0.1213Cochran-Mantel-Haenszel
Comparison: Day 4p-value: 0.0588Cochran-Mantel-Haenszel
Comparison: Day 7p-value: 0.02Cochran-Mantel-Haenszel
Comparison: Day 7p-value: 0.0017Cochran-Mantel-Haenszel
Comparison: Day 14p-value: 0.2401Cochran-Mantel-Haenszel
Comparison: Day 14p-value: 0.0009Cochran-Mantel-Haenszel
Comparison: Day 21p-value: 0.0525Cochran-Mantel-Haenszel
Comparison: Day 21p-value: 0.0025Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Are Y-MRS Remitters at Day 21
Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower.
Time frame: Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 21 | 34.2 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 21 | 38.1 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Remitters at Day 21 | 30.2 Percentage of participants |
p-value: 0.2912Cochran-Mantel-Haenszel
p-value: 0.1151Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21
Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. The analysis is based on a generalized linear mixed model (GLMM). Y-MRS remitters are defined as having a Y-MRS total score of 12 or lower.
Time frame: Day 2, Day 4, Day 7, Day 14, Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 14 (n= 96, 91,102) | 28.1 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 7 (n= 104, 101,110) | 26.9 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 2 (n= 117,111, 123) | 8.5 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 4 (n= 104, 106,118) | 17.3 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 21 (n= 86, 83,93) | 40.7 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 7 (n= 104, 101,110) | 24.8 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 2 (n= 117,111, 123) | 11.7 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 4 (n= 104, 106,118) | 15.1 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 14 (n= 96, 91,102) | 27.5 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 21 (n= 86, 83,93) | 43.4 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 21 (n= 86, 83,93) | 34.4 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 14 (n= 96, 91,102) | 24.5 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 2 (n= 117,111, 123) | 5.7 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 7 (n= 104, 101,110) | 17.3 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Remitters at Day 2, Day 4, Day 7, Day 14, Day 21 | Day 4 (n= 104, 106,118) | 10.2 Percentage of participants |
Secondary
Percentage of Participants Who Are Y-MRS Responders at Day 21
Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by Last Observation Carried Forward (LOCF). Y-MRS responders are defined as having a \>= 50% decrease from baseline in Y-MRS total score.
Time frame: Day 21
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 21 | 45.0 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 21 | 46.9 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Responders at Day 21 | 39.7 Percentage of participants |
p-value: 0.5352Cochran-Mantel-Haenszel
p-value: 0.4274Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14
Y-MRS consists of responses to the following 11 items: elevated mood, increased motor activity energy, sexual interest, sleep, language-thought disorder, appearance, insight, irritability, speech - rate and amount, content and disruptive-aggressive behavior. The scores from the 11 items are summed to give a total score ranging from 0 to 60, with a higher score indicating greater severity of symptoms. Missing data were imputed by LOCF. Y-MRS responders are defined as having a \>= 50% decrease from baseline in Y-MRS total score.
Time frame: Day 2, Day 4, Day 7, Day 14
Population: Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement, and had evaluable post-baseline measurement at timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 2 (n = 117,111,123) | 12.0 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 4 (n = 120,113,126) | 21.7 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 7 (n = 120,113,126) | 31.7 Percentage of participants |
| Asenapine 5 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 14 (n = 120,113,126) | 36.7 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 14 (n = 120,113,126) | 40.7 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 2 (n = 117,111,123) | 14.4 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 7 (n = 120,113,126) | 28.3 Percentage of participants |
| Asenapine 10 mg BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 4 (n = 120,113,126) | 23.0 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 14 (n = 120,113,126) | 33.3 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 4 (n = 120,113,126) | 8.7 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 7 (n = 120,113,126) | 19.8 Percentage of participants |
| Placebo BID | Percentage of Participants Who Are Y-MRS Responders at Day 2, Day 4, Day 7, Day 14 | Day 2 (n = 117,111,123) | 8.9 Percentage of participants |
Comparison: Day 2p-value: 0.2922Cochran-Mantel-Haenszel
Comparison: Day 2p-value: 0.1001Cochran-Mantel-Haenszel
Comparison: Day 4p-value: 0.0011Cochran-Mantel-Haenszel
Comparison: Day 4p-value: 0.0011Cochran-Mantel-Haenszel
Comparison: Day 7p-value: 0.0194Cochran-Mantel-Haenszel
Comparison: Day 7p-value: 0.0841Cochran-Mantel-Haenszel
Comparison: Day 14p-value: 0.4858Cochran-Mantel-Haenszel
Comparison: Day 14p-value: 0.2496Cochran-Mantel-Haenszel