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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-018409-13 | EudraCT Number | ||
| MK-8274-003 | Other Identifier | Merck |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Asenapine 5 mg BID | Experimental | Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days |
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| Asenapine 10 mg BID | Experimental | Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days |
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| Placebo BID | Placebo Comparator | Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Asenapine | Drug | asenapine tablet, 5 mg sublingually BID for 21 days |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Day 21 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26496015 | Result | Landbloom RL, Mackle M, Wu X, Kelly L, Snow-Adami L, McIntyre RS, Mathews M, Hundt C. Asenapine: Efficacy and safety of 5 and 10mg bid in a 3-week, randomized, double-blind, placebo-controlled trial in adults with a manic or mixed episode associated with bipolar I disorder. J Affect Disord. 2016 Jan 15;190:103-110. doi: 10.1016/j.jad.2015.06.059. Epub 2015 Sep 25. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Asenapine 5 mg BID | Participants were administered one 5 mg asenapine tablet, sublingually twice daily (BID) for 21 days |
| FG001 | Asenapine 10 mg BID | Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days |
| FG002 | Placebo BID | Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Randomized participants who received at least one dose of trial medication
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| ID | Title | Description |
|---|---|---|
| BG000 | Asenapine 5 mg BID | Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days |
| BG001 | Asenapine 10 mg BID | Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 21 |
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Up to 33 days after end of treatment (up to 54 days)
Randomized participants who received at least one dose of trial medication
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Asenapine 5 mg BID | Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA Version 17.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| C522667 | asenapine |
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| Asenapine | Drug | asenapine tablet, 10 mg sublingually BID for 21 days |
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| Placebo | Drug | placebo sublingual tablet, administered BID for 21 days |
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| Baseline and Day 21 |
| 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. | Day 21 |
| 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. | Baseline and Day 2, Day 4, Day 7 and Day 14 |
| 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. | Day 2, Day 4, Day 7, Day 14 |
| 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. | Day 21 |
| 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. | Day 2, Day 4, Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7 and Day 21 |
| 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. | Baseline and Day 2, Day 4, Day 7, Day 14 |
| 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. | Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21 |
| 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. | Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21 |
| 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. | Day 2, Day 4, Day 7, Day 14, and Day 21 |
| 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. | Day 2, Day 4, Day 7, Day 14, and Day 21 |
| 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. | Day 2, Day 4, Day 7, Day 14, and Day 21 |
| 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. | Baseline and Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7, Day 14, Day 21 |
| 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. | Baseline and Day 7, Day14, Day 21 |
| Lost to Follow-up |
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| Protocol Violation |
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| BG002 | Placebo BID | Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days |
| BG003 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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Participants were administered one 5 mg asenapine tablet, sublingually BID for 21 days
| OG001 | Asenapine 10 mg BID | Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days |
| OG002 | Placebo BID | Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 21 |
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| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Number | Percentage of participants | Day 21 |
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| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 2, Day 4, Day 7 and Day 14 |
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| 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. | 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. | Posted | Number | Percentage of participants | Day 2, Day 4, Day 7, Day 14 |
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| 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. | Randomized participants who received at least one dose of trial medication and had at least one post-baseline measurement. | Posted | Number | Percentage of participants | Day 21 |
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| 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. | 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. | Posted | Number | Percentage of participants | Day 2, Day 4, Day 7, Day 14, Day 21 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7 and Day 21 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 2, Day 4, Day 7, Day 14 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 2, Day 4, Day 7, Day 14, and Day 21 |
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| 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. | 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. | Posted | Number | Percentage of participants | Day 2, Day 4, Day 7, Day 14, and Day 21 |
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| 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. | 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. | Posted | Number | Percentage of participants | Day 2, Day 4, Day 7, Day 14, and Day 21 |
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| 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. | 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. | Posted | Number | Percentage of participants | Day 2, Day 4, Day 7, Day 14, and Day 21 |
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| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day 14, Day 21 |
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| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day 14, Day 21 |
|
|
|
|
| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day 14, Day 21 |
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|
|
|
| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day 14, Day 21 |
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|
|
| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day 14, Day 21 |
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|
| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day 14, Day 21 |
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|
| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day 14, Day 21 |
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|
|
|
| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day 14, Day 21 |
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|
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| 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. | Randomized participants who received at least one dose of trial medication and had at least one baseline and post-baseline measurement. | Posted | Least Squares Mean | Standard Error | Score on a scale | Baseline and Day 7, Day14, Day 21 |
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|
|
|
| 3 |
| 122 |
| 43 |
| 122 |
| EG001 | Asenapine 10 mg BID | Participants were administered one 10 mg asenapine tablet, sublingually BID for 21 days | 1 | 119 | 67 | 119 |
| EG002 | Placebo BID | Participants were administered one asenapine-matched placebo tablet sublingually BID for 21 days | 2 | 126 | 24 | 126 |
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA Version 17.0 | Systematic Assessment |
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| Foot fracture | Injury, poisoning and procedural complications | MedDRA Version 17.0 | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA Version 17.0 | Systematic Assessment |
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| Bipolar I disorder | Psychiatric disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Mania | Psychiatric disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Suicide attempt | Psychiatric disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Increased appetite | Metabolism and nutrition disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Akathisia | Nervous system disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Sedation | Nervous system disorders | MedDRA Version 17.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA Version 17.0 | Systematic Assessment |
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The investigator agrees to provide to the sponsor 45 days to submission for publication or presentation, review copies of abstracts or manuscripts for publication (including without limitation, slides and texts of oral or other public presentations and texts of any transmission through any electronic media, eg, any computer access system such as the Internet, World Wide Web, etc) that report any results of the trial.
| MMRM |
| 0.0052 |
Adjusted p-value from Hochberg's method for testing two secondary efficacy hypotheses |
| LS means difference |
| -0.5 |
| Standard Error of the Mean |
| 0.16 |
| 2-Sided |
| 95 |
| -0.9 |
| -0.2 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| 0.4274 |
Overall adjusted p-value from Hochberg's method for testing two secondary efficacy hypotheses |
| Superiority or Other (legacy) |
|
| Day 7 |
|
| Day 14 |
|
Day 2
| MMRM |
| 0.0003 |
| LS means difference |
| -2.9 |
| Standard Error of the Mean |
| 0.79 |
| 2-Sided |
| 95 |
| -4.4 |
| -1.3 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 4 | MMRM | <0.0001 | LS means difference | -3.6 | Standard Error of the Mean | 0.91 | 2-Sided | 95 | -5.4 | -1.8 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 4 | MMRM | <0.0001 | LS means difference | -3.7 | Standard Error of the Mean | 0.92 | 2-Sided | 95 | -5.5 | -1.9 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 7 | MMRM | 0.0021 | LS means difference | -3.5 | Standard Error of the Mean | 1.12 | 2-Sided | 95 | -5.7 | -1.3 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 7 | MMRM | 0.0002 | LS means difference | -4.2 | Standard Error of the Mean | 1.13 | 2-Sided | 95 | -6.4 | -2.0 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.1907 | LS means difference | -1.8 | Standard Error of the Mean | 1.35 | 2-Sided | 95 | -4.4 | 0.9 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0238 | LS means difference | -3.1 | Standard Error of the Mean | 1.37 | 2-Sided | 95 | -5.8 | -0.4 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 7 (n = 120,113,126) |
|
| Day 14 (n = 120,113,126) |
|
| 0.1001 |
| Superiority or Other (legacy) |
| Day 4 | Cochran-Mantel-Haenszel | 0.0011 | Superiority or Other (legacy) |
| Day 4 | Cochran-Mantel-Haenszel | 0.0011 | Superiority or Other (legacy) |
| Day 7 | Cochran-Mantel-Haenszel | 0.0194 | Superiority or Other (legacy) |
| Day 7 | Cochran-Mantel-Haenszel | 0.0841 | Superiority or Other (legacy) |
| Day 14 | Cochran-Mantel-Haenszel | 0.4858 | Superiority or Other (legacy) |
| Day 14 | Cochran-Mantel-Haenszel | 0.2496 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
|
| Day 7 (n= 104, 101,110) |
|
| Day 14 (n= 96, 91,102) |
|
| Day 21 (n= 86, 83,93) |
|
|
| 0.0045 |
| Superiority or Other (legacy) |
| Day 21 | ANCOVA | 0.0112 | Superiority or Other (legacy) |
| Day 21 | ANCOVA | 0.0021 | Superiority or Other (legacy) |
|
| Day 7 |
|
| Day 14 |
|
Day 2
| MMRM |
| 0.0076 |
| LS means difference |
| -0.2 |
| Standard Error of the Mean |
| 0.07 |
| 2-Sided |
| 95 |
| -0.3 |
| -0.1 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 4 | MMRM | 0.0004 | LS means difference | -0.4 | Standard Error of the Mean | 0.10 | 2-Sided | 95 | -0.6 | -0.2 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 4 | MMRM | 0.0040 | LS means difference | -0.3 | Standard Error of the Mean | 0.10 | 2-Sided | 95 | -0.5 | -0.1 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 7 | MMRM | 0.0061 | LS means difference | -0.3 | Standard Error of the Mean | 0.12 | 2-Sided | 95 | -0.6 | -0.1 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 7 | MMRM | 0.0031 | LS means difference | -0.4 | Standard Error of the Mean | 0.13 | 2-Sided | 95 | -0.6 | -0.1 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.1086 | LS means difference | -0.2 | Standard Error of the Mean | 0.14 | 2-Sided | 95 | -0.5 | 0.1 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0376 | LS means difference | -0.3 | Standard Error of the Mean | 0.15 | 2-Sided | 95 | -0.6 | -0.0 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 7 (n=120,113,125) |
|
| Day 14 (n=120,113,125) |
|
| Day 21 (n=120,113,125) |
|
| 0.0026 |
| Superiority or Other (legacy) |
| Day 4 | ANCOVA | 0.0007 | Superiority or Other (legacy) |
| Day 4 | ANCOVA | 0.0002 | Superiority or Other (legacy) |
| Day 7 | ANCOVA | 0.0387 | Superiority or Other (legacy) |
| Day 7 | ANCOVA | 0.0059 | Superiority or Other (legacy) |
| Day 14 | ANCOVA | 0.3110 | Superiority or Other (legacy) |
| Day 14 | ANCOVA | 0.0613 | Superiority or Other (legacy) |
| Day 21 | ANCOVA | 0.0640 | Superiority or Other (legacy) |
| Day 21 | ANCOVA | 0.0139 | Superiority or Other (legacy) |
|
| Day 7 (n=120,113,125) |
|
| Day 14 (n=120,113,125) |
|
| Day 21 (n=120,113,125) |
|
| 0.7891 |
| Superiority or Other (legacy) |
| Day 4 | ANCOVA | 0.5222 | Superiority or Other (legacy) |
| Day 4 | ANCOVA | 0.8686 | Superiority or Other (legacy) |
| Day 7 | ANCOVA | 0.0696 | Superiority or Other (legacy) |
| Day 7 | ANCOVA | 0.0049 | Superiority or Other (legacy) |
| Day 14 | ANCOVA | 0.0196 | Superiority or Other (legacy) |
| Day 14 | ANCOVA | 0.0032 | Superiority or Other (legacy) |
| Day 21 | ANCOVA | 0.0061 | Superiority or Other (legacy) |
| Day 21 | ANCOVA | 0.0012 | Superiority or Other (legacy) |
|
| Day 7 (n=120,113,126) |
|
| Day 14 (n=120,113,126) |
|
| Day 21 (n=120,113,126) |
|
| 0.0720 |
| Superiority or Other (legacy) |
| Day 4 | Cochran-Mantel-Haenszel | 0.1213 | Superiority or Other (legacy) |
| Day 4 | Cochran-Mantel-Haenszel | 0.0588 | Superiority or Other (legacy) |
| Day 7 | Cochran-Mantel-Haenszel | 0.0200 | Superiority or Other (legacy) |
| Day 7 | Cochran-Mantel-Haenszel | 0.0017 | Superiority or Other (legacy) |
| Day 14 | Cochran-Mantel-Haenszel | 0.2401 | Superiority or Other (legacy) |
| Day 14 | Cochran-Mantel-Haenszel | 0.0009 | Superiority or Other (legacy) |
| Day 21 | Cochran-Mantel-Haenszel | 0.0525 | Superiority or Other (legacy) |
| Day 21 | Cochran-Mantel-Haenszel | 0.0025 | Superiority or Other (legacy) |
|
| Day 7 (n=120,113,126) |
|
| Day 14 (n=120,113,126) |
|
| Day 21 (n=120,113,126) |
|
| 0.0771 |
| Superiority or Other (legacy) |
| Day 4 | Cochran-Mantel-Haenszel | 0.1264 | Superiority or Other (legacy) |
| Day 4 | Cochran-Mantel-Haenszel | 0.0280 | Superiority or Other (legacy) |
| Day 7 | Cochran-Mantel-Haenszel | 0.0583 | Superiority or Other (legacy) |
| Day 7 | Cochran-Mantel-Haenszel | 0.0021 | Superiority or Other (legacy) |
| Day 14 | Cochran-Mantel-Haenszel | 0.0866 | Superiority or Other (legacy) |
| Day 14 | Cochran-Mantel-Haenszel | 0.0048 | Superiority or Other (legacy) |
| Day 21 | Cochran-Mantel-Haenszel | 0.0147 | Superiority or Other (legacy) |
| Day 21 | Cochran-Mantel-Haenszel | 0.0030 | Superiority or Other (legacy) |
|
| Day 7 (n=117, 106, 119) |
|
| Day 14 (n=117, 106, 120) |
|
| Day 21 (n=117, 106, 121) |
|
| 0.0005 |
| Superiority or Other (legacy) |
| Day 4 | Cochran-Mantel-Haenszel | 0.0692 | Superiority or Other (legacy) |
| Day 4 | Cochran-Mantel-Haenszel | 0.0128 | Superiority or Other (legacy) |
| Day 7 | Cochran-Mantel-Haenszel | 0.0809 | Superiority or Other (legacy) |
| Day 7 | Cochran-Mantel-Haenszel | 0.0260 | Superiority or Other (legacy) |
| Day 14 | Cochran-Mantel-Haenszel | 0.2576 | Superiority or Other (legacy) |
| Day 14 | Cochran-Mantel-Haenszel | 0.0077 | Superiority or Other (legacy) |
| Day 21 | Cochran-Mantel-Haenszel | 0.3960 | Superiority or Other (legacy) |
| Day 21 | Cochran-Mantel-Haenszel | 0.0141 | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.0068 |
| LS means difference |
| -2.9 |
| Standard Error of the Mean |
| 1.08 |
| 2-Sided |
| 95 |
| -5.0 |
| -0.8 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0743 | LS means difference | -2.4 | Standard Error of the Mean | 1.33 | 2-Sided | 95 | -5.0 | 0.2 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0177 | LS means difference | -3.2 | Standard Error of the Mean | 1.35 | 2-Sided | 95 | -5.9 | -0.6 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0081 | LS means difference | -3.8 | Standard Error of the Mean | 1.41 | 2-Sided | 95 | -6.6 | -1.0 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0247 | LS means difference | -3.2 | Standard Error of the Mean | 1.43 | 2-Sided | 95 | -6.1 | -0.4 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.2830 |
| LS means difference |
| -0.3 |
| Standard Error of the Mean |
| 0.31 |
| 2-Sided |
| 95 |
| -0.9 |
| 0.3 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.9751 | LS means difference | -0.0 | Standard Error of the Mean | 0.32 | 2-Sided | 95 | -0.6 | 0.6 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.7879 | LS means difference | 0.1 | Standard Error of the Mean | 0.33 | 2-Sided | 95 | -0.6 | 0.7 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.9654 | LS means difference | -0.0 | Standard Error of the Mean | 0.38 | 2-Sided | 95 | -0.8 | 0.7 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.3917 | LS means difference | 0.3 | Standard Error of the Mean | 0.39 | 2-Sided | 95 | -0.4 | 1.1 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.0011 |
| LS means difference |
| -1.4 |
| Standard Error of the Mean |
| 0.42 |
| 2-Sided |
| 95 |
| -2.2 |
| -0.5 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.6885 | LS means difference | -0.2 | Standard Error of the Mean | 0.51 | 2-Sided | 95 | -1.2 | 0.8 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0398 | LS means difference | -1.1 | Standard Error of the Mean | 0.52 | 2-Sided | 95 | -2.1 | -0.1 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0258 | LS means difference | -1.1 | Standard Error of the Mean | 0.51 | 2-Sided | 95 | -2.1 | -0.1 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0031 | LS means difference | -1.5 | Standard Error of the Mean | 0.51 | 2-Sided | 95 | -2.5 | -0.5 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.0622 |
| LS means difference |
| -1.2 |
| Standard Error of the Mean |
| 0.65 |
| 2-Sided |
| 95 |
| -2.5 |
| 0.1 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0083 | LS means difference | -2.1 | Standard Error of the Mean | 0.79 | 2-Sided | 95 | -3.6 | -0.5 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0064 | LS means difference | -2.2 | Standard Error of the Mean | 0.80 | 2-Sided | 95 | -3.8 | -0.6 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0022 | LS means difference | -2.6 | Standard Error of the Mean | 0.84 | 2-Sided | 95 | -4.3 | -0.9 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0196 | LS means difference | -2.0 | Standard Error of the Mean | 0.85 | 2-Sided | 95 | -3.7 | -0.3 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.1684 |
| LS means difference |
| -0.6 |
| Standard Error of the Mean |
| 0.40 |
| 2-Sided |
| 95 |
| -1.3 |
| 0.2 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.9522 | LS means difference | -0.0 | Standard Error of the Mean | 0.46 | 2-Sided | 95 | -0.9 | 0.9 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0514 | LS means difference | -0.9 | Standard Error of the Mean | 0.47 | 2-Sided | 95 | -1.8 | 0.0 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0531 | LS means difference | -0.9 | Standard Error of the Mean | 0.47 | 2-Sided | 95 | -1.8 | 0.0 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0078 | LS means difference | -1.3 | Standard Error of the Mean | 0.48 | 2-Sided | 95 | -2.2 | -0.3 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.2754 |
| LS means difference |
| -0.4 |
| Standard Error of the Mean |
| 0.32 |
| 2-Sided |
| 95 |
| -1.0 |
| 0.3 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.9109 | LS means difference | 0.0 | Standard Error of the Mean | 0.34 | 2-Sided | 95 | -0.6 | 0.7 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.7295 | LS means difference | 0.1 | Standard Error of the Mean | 0.34 | 2-Sided | 95 | -0.6 | 0.8 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.9800 | LS means difference | 0.0 | Standard Error of the Mean | 0.38 | 2-Sided | 95 | -0.7 | 0.8 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.5122 | LS means difference | 0.3 | Standard Error of the Mean | 0.38 | 2-Sided | 95 | -0.5 | 1.0 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.0589 |
| LS means difference |
| -0.6 |
| Standard Error of the Mean |
| 0.29 |
| 2-Sided |
| 95 |
| -1.1 |
| 0.0 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.3683 | LS means difference | -0.3 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -1.0 | 0.4 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0982 | LS means difference | -0.6 | Standard Error of the Mean | 0.37 | 2-Sided | 95 | -1.3 | 0.1 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.1969 | LS means difference | -0.5 | Standard Error of the Mean | 0.38 | 2-Sided | 95 | -1.3 | 0.3 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.5615 | LS means difference | -0.2 | Standard Error of the Mean | 0.39 | 2-Sided | 95 | -1.0 | 0.5 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.0146 |
| LS means difference |
| -0.8 |
| Standard Error of the Mean |
| 0.34 |
| 2-Sided |
| 95 |
| -1.5 |
| -0.2 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0861 | LS means difference | -0.7 | Standard Error of the Mean | 0.39 | 2-Sided | 95 | -1.4 | 0.1 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0342 | LS means difference | -0.8 | Standard Error of the Mean | 0.39 | 2-Sided | 95 | -1.6 | -0.1 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0037 | LS means difference | -1.2 | Standard Error of the Mean | 0.40 | 2-Sided | 95 | -2.0 | -0.4 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0096 | LS means difference | -1.1 | Standard Error of the Mean | 0.41 | 2-Sided | 95 | -1.9 | -0.3 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
|
| Day 21 |
|
Day 7
| MMRM |
| 0.0791 |
| LS means difference |
| -0.6 |
| Standard Error of the Mean |
| 0.33 |
| 2-Sided |
| 95 |
| -1.2 |
| 0.1 |
Asenapine 10 mg BID minus Placebo BID |
| Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0006 | LS means difference | -1.2 | Standard Error of the Mean | 0.36 | 2-Sided | 95 | -2.0 | -0.5 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 14 | MMRM | 0.0123 | LS means difference | -0.9 | Standard Error of the Mean | 0.37 | 2-Sided | 95 | -1.6 | -0.2 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0054 | LS means difference | -1.1 | Standard Error of the Mean | 0.41 | 2-Sided | 95 | -2.0 | -0.3 | Asenapine 5 mg BID minus Placebo BID | Superiority or Other (legacy) |
| Day 21 | MMRM | 0.0350 | LS means difference | -0.9 | Standard Error of the Mean | 0.41 | 2-Sided | 95 | -1.7 | -0.1 | Asenapine 10 mg BID minus Placebo BID | Superiority or Other (legacy) |