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Efficacy and safety of asenapine for the treatment of bipolar I disorder (manic or mixed episodes) will be evaluated in participants between 10 and 17 years old, who are either hospitalized or non-hospitalized. In this 3-weeks, double-blind, parallel design trial, eligible participants will be randomized to receive one out of three fixed dose levels of asenapine, or placebo. The study primary hypothesis is that at least one asenapine dose is superior to placebo as measured by the change from baseline to Day 21 in Young Mania Rating Scale (Y-MRS) total score. Trial medication and placebo are provided as identical-looking sublingual tablets; concurrent use of psychotropics is prohibited, except use of short-acting benzodiazepines and psychostimulants approved for the treatment of attention deficit hyperactivity disorder (ADHD). Main treatment effect is measured using Y-MRS and safety is evaluated using the recordings of adverse events, routine blood panels, physical examinations (including vital signs), and electrocardiograms. Participants who complete the double blind trial may be offered to continue (open-label) treatment with asenapine for an extended period of time. Follow-up information on safety parameters will be collected in all participants within 30 days following treatment discontinuation.
Participants' Y-MRS total score at baseline will be subtracted from that at the Day 21 visit to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The Y-MRS is an 11 item scale: seven items ranked on scale from 0 to 4 and four items ranked 0 to 8 with a range of possible total scores from 0 to 60.
Participants' overall score on the CGI-BP at Day 21 will be evaluated to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. CGI-BP overall score is obtained from a single-item clinician-rated scale used to assess the participant's overall bipolar illness. Scores range from not ill (1) to very severely ill (7).
The proportion of participants whose total Y-MRS score is decreased ≥50% from baseline at Day 4, 7, 14 and 21. Results for the 3 different asenapine doses compared to placebo will be evaluated.
Participants' mania sub-score from the CGI-BP will be evaluated for each study visit (Days 4, 7, 14 and 21) to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated.
Participants' depression sub-score from the CGI-BP will evaluated at each study visit (Days 4, 7, 14 and 21) to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated.
Participants' CDRS-R at baseline will be subtracted from those at each study visit at which this rating was measured (Days 7, 14 and 21) to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The CDRS-R is a 17-item scale that assesses the presence and severity of depressive symptoms: fourteen items are rated from 1 to 7 and three items are rated from 1 to 5; total scores range from 17 to 113.
Participants' CGAS at baseline will be subtracted from that at the Day 21 visit to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The CGAS is a 100-point scale, with a possible range of 1 to 100. Normal social functioning is defined as a CGAS total score of ≥70.
Participants' PQ-LES-Q total score at baseline will be subtracted from that at the Day 21 visit to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The PQ-LES-Q is a 15-item scale, with total score calculated as the sum of the first 14 items, with a range of 14 to 70. Each item is scored by the child from 1 to 5, with higher scores indicative of greater enjoyment and satisfaction.
Participants' PQ-LES-Q overall score (i.e. item 15) at baseline will be subtracted from that at the Day 21 visit to determine the amount of change over time with treatment. The responses for the 3 different asenapine doses compared to placebo will be evaluated. The PQ-LES-Q overall score is determined by the answer to item 15 on the questionnaire (range: 1 to 5).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Asenapine 2.5 mg twice daily (BID) | Experimental | Participants receive asenapine 2.5 mg BID for 21 days. |
|
| Asenapine 5.0 mg BID | Experimental | Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period. |
|
| Asenapine 10.0 mg BID | Experimental | Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period. |
|
| Placebo | Placebo Comparator | Participants receive placebo BID for 21 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| asenapine | Drug | Asenapine tablets, administered sublingually twice daily at one of three dose levels (2.5 mg, 5.0 mg, or 10.0 mg) |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Y-MRS Total Score at Day 21 | The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Baseline and Day 21 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Clinical Global Impression Scale for Use in Bipolar Disorder (CGI-BP) Overall Score at Day 21 | Change from baseline in CGI-BP overall score at Day 21 is the Key Secondary Outcome Measure. The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the participant's overall bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. |
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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 |
|---|---|---|---|
| 26598478 | Derived | Findling RL, Landbloom RL, Szegedi A, Koppenhaver J, Braat S, Zhu Q, Mackle M, Chang K, Mathews M. Asenapine for the Acute Treatment of Pediatric Manic or Mixed Episode of Bipolar I Disorder. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):1032-41. doi: 10.1016/j.jaac.2015.09.007. Epub 2015 Oct 24. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants receive placebo twice daily (BID) for 21 days. |
| FG001 | Asenapine 2.5 mg BID | Participants receive asenapine 2.5 mg BID for 21 days. |
| FG002 | Asenapine 5.0 mg BID | Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period. |
| FG003 | Asenapine 10.0 mg BID | Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The population consisted of all randomized participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants receive placebo BID for 21 days. |
| BG001 | Asenapine 2.5 mg BID | Participants receive asenapine 2.5 mg 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 Y-MRS Total Score at Day 21 | The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy Full Analysis Set [FAS]); also, to be included an on-treatment Day 21 value of Y-MRS total score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 21 |
Up to 30 days after the last dose of study drug (Up to 51 days)
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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 | Placebo | Participants receive placebo BID for 21 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| BIPOLAR DISORDER | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 16.0 | 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 |
|---|---|
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C522667 | asenapine |
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| Placebo to match asenapine | Drug | Placebo tablets to match asenapine tablets, administered sublingually twice daily |
|
| Rescue medication | Drug | For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines and EPS medications (i.e., anticholinergics) are allowed. Benadryl (diphenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments. |
|
| Baseline and Day 21 |
| Total Y-MRS 50% Responders at Days 4, 7, 14 and 21 | A total Y-MRS 50% responder was defined as a participant who had a reduction from baseline to the identified study visit of at least 50% in the Y-MRS total score. The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items, based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60 with higher scores indicating greater severity of symptoms. This analysis used a Last-Observation-Carried-Forward (LOCF) approach; if at a given visit no Y-MRS total score was available for determining whether a participant was a responder, the last available post-baseline on-treatment assessment prior to that visit was used. | Baseline and Days 4, 7, 14 and 21 |
| Change From Baseline in CGI-BP Mania Score at Day 4 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 4; improvement in symptoms is represented by negative values. | Baseline and Day 4 |
| Change From Baseline in CGI-BP Mania Score at Day 7 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values. | Baseline and Day 7 |
| Change From Baseline in CGI-BP Mania Score at Day 14 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values. | Baseline and Day 14 |
| Change From Baseline in CGI-BP Mania Score at Day 21 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Baseline and Day 21 |
| Change From Baseline in CGI-BP Depression Score at Day 4 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 4; improvement in symptoms is represented by negative values. | Baseline and Day 4 |
| Change From Baseline in CGI-BP Depression Score at Day 7 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values. | Baseline and Day 7 |
| Change From Baseline in CGI-BP Depression Score at Day 14 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values. | Baseline and Day 14 |
| Change From Baseline in CGI-BP Depression Score at Day 21 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Baseline and Day 21 |
| Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score at Day 7 | The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values. | Baseline and Day 7 |
| Change From Baseline in CDRS-R Total Score at Day 14 | The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values. | Baseline and Day 14 |
| Change From Baseline in CDRS-R Total Score at Day 21 | The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Baseline and Day 21 |
| Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 21 | CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The reported measure is the change from baseline at Day 21; improvement in functioning is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used. | Baseline and Day 21 |
| Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 21 | PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant was calculated as the sum of the rating assigned to each of the first 14 items, and ranged from 14 to 70 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used. | Baseline and Day 21 |
| Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 21 | PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The Item 15 result is defined to be the PQ-LES-Q overall score, and ranged from 1 to 5 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used. | Baseline and Day 21 |
| Adverse Event |
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| Treatment Failure |
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| Lost to Follow-up |
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| Withdrawal by Subject |
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| Protocol Violation |
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| Did Not Meet Protocol Eligibility |
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| BG002 | Asenapine 5.0 mg BID | Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period. |
| BG003 | Asenapine 10.0 mg BID | Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Young Mania Rating Scale (Y-MRS) total score | Y-MRS is an 11-item instrument for assessing the severity of manic episodes. Seven of the 11 items are rated on a scale of 0-4 and 4 are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60. Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively. | Mean | Standard Deviation | score on a scale |
|
| Clinical Global Impression Scale for use in Bipolar Disorder (CGI-BP) overall score | CGI-BP overall score is obtained using a 7-point scale assessing the severity of the participant's overall bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. Summary statistics presented are for efficacy population (FAS): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively. | Mean | Standard Deviation | score on a scale |
|
| CGI-BP mania score | CGI-BP mania score is obtained using a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. Summary statistics presented are for efficacy population (FAS): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively. | Mean | Standard Deviation | score on a scale |
|
| CGI-BP depression score | CGI-BP depression score is obtained using a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. Summary statistics presented are for efficacy population (FAS) except as noted: N=97 (baseline value not available for 1 FAS participant in this group), 101, 98, 98 and 394 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively. | Mean | Standard Deviation | score on a scale |
|
| Children's Depression Rating Scale, Revised (CDRS-R) total score | CDRS-R is a 17-item instrument for assessing depression in children. Items are rated on a scale of 1-7 (14 items) or 1-5 (3 items); higher scores indicate more severe symptoms. CDRS-R total score is sum of ratings for the 17 items (range: 17-113). Summary statistics presented are for efficacy population (FAS) except as noted: N=97 (baseline value not available for 1 FAS participant in this group), 99 (baseline value not available for 2 FAS participants in this group), 98, 98 and 392 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively. | Mean | Standard Deviation | score on a scale |
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| Children's Global Assessment Scale (CGAS) total score - current functioning | CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively. | Mean | Standard Deviation | score on a scale |
|
| Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total score | PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life on a scale of 1=very poor to 5=very good. The PQ-LES-Q total score (sum of Items 1-14) ranged from 14 to 70 with a higher score indicating better quality of life. Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively. | Mean | Standard Deviation | score on a scale |
|
| PQ-LES-Q overall score (i.e., item 15) | PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life on a scale of 1=very poor to 5=very good. The PQ-LES-Q overall score (Item 15, a global assessment of quality of life) ranged from 1 to 5 with a higher score indicating better quality of life. Summary statistics presented are for efficacy population (Full Analysis Set [FAS]): N=98, 101, 98, 98 and 395 for Placebo, asenapine 2.5 mg BID, asenapine 5.0 mg BID, asenapine 10.0 mg BID and Total groups, respectively. | Mean | Standard Deviation | score on a scale |
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| Secondary | Change From Baseline in Clinical Global Impression Scale for Use in Bipolar Disorder (CGI-BP) Overall Score at Day 21 | Change from baseline in CGI-BP overall score at Day 21 is the Key Secondary Outcome Measure. The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the participant's overall bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP overall score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 21 |
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| Secondary | Total Y-MRS 50% Responders at Days 4, 7, 14 and 21 | A total Y-MRS 50% responder was defined as a participant who had a reduction from baseline to the identified study visit of at least 50% in the Y-MRS total score. The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items, based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60 with higher scores indicating greater severity of symptoms. This analysis used a Last-Observation-Carried-Forward (LOCF) approach; if at a given visit no Y-MRS total score was available for determining whether a participant was a responder, the last available post-baseline on-treatment assessment prior to that visit was used. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included for a visit, a Y-MRS total score must be available for that visit or a prior post-baseline on-treatment visit | Posted | Number | participants | Baseline and Days 4, 7, 14 and 21 |
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| Secondary | Change From Baseline in CGI-BP Mania Score at Day 4 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 4; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 4 value of CGI-BP mania score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 4 |
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| Secondary | Change From Baseline in CGI-BP Mania Score at Day 7 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CGI-BP mania score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 7 |
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| Secondary | Change From Baseline in CGI-BP Mania Score at Day 14 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CGI-BP mania score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 14 |
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| Secondary | Change From Baseline in CGI-BP Mania Score at Day 21 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the mania component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP mania score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 21 |
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| Secondary | Change From Baseline in CGI-BP Depression Score at Day 4 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 4; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 4 value of CGI-BP depression score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 4 |
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| Secondary | Change From Baseline in CGI-BP Depression Score at Day 7 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CGI-BP depression score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 7 |
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| Secondary | Change From Baseline in CGI-BP Depression Score at Day 14 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CGI-BP depression score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 14 |
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| Secondary | Change From Baseline in CGI-BP Depression Score at Day 21 | The CGI-BP is a clinician-rated instrument for assessing bipolar illness that includes subscales assessing mania and depression. This measure reports one item within the CGI-BP, which is a 7-point scale assessing the severity of the depression component of the participant's bipolar illness, with ratings from 1=normal, not ill to 7=very severely ill. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CGI-BP depression score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 21 |
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| Secondary | Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score at Day 7 | The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 7; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 7 value of CDRS-R total score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 7 |
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| Secondary | Change From Baseline in CDRS-R Total Score at Day 14 | The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 14; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 14 value of CDRS-R total score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 14 |
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| Secondary | Change From Baseline in CDRS-R Total Score at Day 21 | The CDRS-R is a 17-item clinician-rated instrument for assessing the presence and severity of depressive symptoms in children. Fourteen of the 17 items are rated on a scale of 1-7 and 3 of the items are rated on a scale of 1-5, with higher scores indicating greater severity of symptoms. The CDRS-R total score for each participant is the sum of the ratings for the 17 individual items, and can range from 17-113, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and an on-treatment Day 21 value of CDRS-R total score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 21 |
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| Secondary | Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 21 | CGAS is a 100-point scale measuring psychological, social, and school functioning in children aged 6-17. Minimum scores ranged from 1-10, representing the need for constant supervision (worse result) to maximum scores of 91-100, representing superior functioning (better result). The reported measure is the change from baseline at Day 21; improvement in functioning is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of CGAS score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 21 |
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| Secondary | Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 21 | PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The PQ-LES-Q total score for each participant was calculated as the sum of the rating assigned to each of the first 14 items, and ranged from 14 to 70 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of PQ-LES-Q total score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 21 |
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| Secondary | Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 21 | PQ-LES-Q is a questionnaire to assess quality of life enjoyment and satisfaction in children and adolescents. The participant is asked to rate 15 items reflecting quality of life with respect to the previous week on a scale of 1=very poor to 5=very good. Items 1-14 assess specific areas (e.g., your health, your mood or feelings); Item 15 is a global assessment of overall quality of life. The Item 15 result is defined to be the PQ-LES-Q overall score, and ranged from 1 to 5 with a higher score indicating better quality of life. The reported measure is the change from baseline at Day 21; improvement in quality of life is represented by positive values. This analysis used an LOCF approach; if no Day 21 value was available for a participant, the last available post-baseline on-treatment assessment prior to the Day 21 assessment was used. | Randomized participants who received at least 1 dose of study drug and had both a baseline and at least 1 post-baseline on-treatment Y-MRS total score (this group is termed the efficacy FAS); also, to be included a baseline and at least 1 post-baseline on-treatment value of PQ-LES-Q overall score must be available for a participant. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Day 21 |
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| 3 |
| 101 |
| 30 |
| 101 |
| EG001 | Asenapine 2.5 mg BID | Participants receive asenapine 2.5 mg BID for 21 days. | 0 | 104 | 68 | 104 |
| EG002 | Asenapine 5.0 mg BID | Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period. | 2 | 99 | 70 | 99 |
| EG003 | Asenapine 10.0 mg BID | Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period. | 2 | 99 | 72 | 99 |
| BIPOLAR I DISORDER | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| MANIA | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| SUICIDAL BEHAVIOUR | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| SUICIDAL IDEATION | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| SUICIDE ATTEMPT | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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| HYPOAESTHESIA ORAL | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| PARAESTHESIA ORAL | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
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| FATIGUE | General disorders | MedDRA 16.0 | Systematic Assessment |
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| WEIGHT INCREASED | Investigations | MedDRA 16.0 | Systematic Assessment |
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| INCREASED APPETITE | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| DYSGEUSIA | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| SEDATION | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| SOMNOLENCE | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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It is planned to first publish/present trial results together with the other sites, unless permission is obtained from Sponsor to publish separate results. Sponsor must be able to review all proposed results communications regarding study 45 days prior to submission for publication/presentation. If there is disagreement concerning appropriateness of the materials, Investigator and Sponsor must meet to make a good faith effort to discuss/resolve disagreement prior to submission for publication.
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | <0.001 | p-value is adjusted by Hochberg's method for testing three asenapine groups versus the placebo group | Difference in LS Means | -0.7 | 2-Sided | 95 | -0.9 | -0.4 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | <0.001 | p-value is adjusted by Hochberg's method for testing three asenapine groups versus the placebo group | Difference in LS Means | -0.7 | 2-Sided | 95 | -1.0 | -0.4 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Day 7 (n=98, 101, 98, 98) |
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| Day 14 (n=98, 101, 98, 98) |
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| Day 21 (n=98, 101, 98, 98) |
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| Analysis is for asenapine versus placebo on Day 4 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | 0.008 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 3.4 | 2-Sided | 95 | 1.4 | 8.6 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 4 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | 0.129 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 2.1 | 2-Sided | 95 | 0.8 | 5.6 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 7 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | 0.003 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 2.9 | 2-Sided | 95 | 1.4 | 5.9 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 7 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | 0.005 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 2.8 | 2-Sided | 95 | 1.4 | 5.6 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 7 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | <0.001 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 3.6 | 2-Sided | 95 | 1.8 | 7.3 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 14 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | 0.018 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 2.2 | 2-Sided | 95 | 1.1 | 4.1 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 14 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | <0.001 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 4.1 | 2-Sided | 95 | 2.2 | 7.6 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 14 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | <0.001 | Odds Ratio (OR) | 4.1 | 2-Sided | 95 | 2.2 | 7.6 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 21 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | 0.042 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 1.9 | 2-Sided | 95 | 1.0 | 3.4 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 21 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | <0.001 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 3.2 | 2-Sided | 95 | 1.7 | 5.8 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Analysis is for asenapine versus placebo on Day 21 (LOCF) | Regression, Logistic | Model included terms of treatment and baseline Y-MRS total score | <0.001 | 95% Confidence Interval and p-value are based on Wald statistic | Odds Ratio (OR) | 2.9 | 95 | 1.6 | 5.3 | OR was adjusted for baseline. An OR of >1 is considered to mean that asenapine has a higher probability of achieving Total Y-MRS 50% response. | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.107 | Difference in LS Means | -0.17 | 2-Sided | 95 | -0.37 | 0.04 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.039 | Difference in LS Means | -0.21 | 2-Sided | 95 | -0.42 | -0.01 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.003 | Difference in LS Means | -0.35 | 2-Sided | 95 | -0.59 | -0.12 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | <0.001 | Difference in LS Means | -0.44 | 2-Sided | 95 | -0.67 | -0.21 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | <0.001 | Difference in LS Means | -0.63 | 2-Sided | 95 | -0.89 | -0.36 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | <0.001 | Difference in LS Means | -0.61 | 2-Sided | 95 | -0.88 | -0.35 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | <0.001 | Difference in LS Means | -0.75 | 2-Sided | 95 | -1.04 | -0.46 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | <0.001 | Difference in LS Means | -0.74 | 2-Sided | 95 | -1.03 | -0.45 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.811 | Difference in LS Means | -0.03 | 2-Sided | 95 | -0.24 | 0.19 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.556 | Difference in LS Means | 0.07 | 2-Sided | 95 | -0.15 | 0.28 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.094 | Difference in LS Means | -0.18 | 2-Sided | 95 | -0.40 | 0.03 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.178 | Difference in LS Means | -0.15 | 2-Sided | 95 | -0.36 | 0.07 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.131 | Difference in LS Means | -0.19 | 2-Sided | 95 | -0.43 | 0.06 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.211 | Difference in LS Means | -0.16 | 2-Sided | 95 | -0.40 | 0.09 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.010 | Difference in LS Means | -0.34 | 2-Sided | 95 | -0.60 | -0.08 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.139 | Difference in LS Means | -0.20 | 2-Sided | 95 | -0.46 | 0.06 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.017 | Difference in LS Means | -2.17 | 2-Sided | 95 | -3.95 | -0.39 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.017 | Difference in LS Means | -2.16 | 2-Sided | 95 | -3.93 | -0.38 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.009 | Difference in LS Means | -2.44 | 2-Sided | 95 | -4.26 | -0.63 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.121 | Difference in LS Means | -1.44 | 2-Sided | 95 | -3.27 | 0.38 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.023 | Difference in LS Means | -2.19 | 2-Sided | 95 | -4.08 | -0.30 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| Model uses efficacy FAS population (number of participants: placebo - 98, asenapine 2.5 mg - 101, asenapine 5.0 mg - 98, asenapine 10.0 mg - 98) | MMRM | Model included terms of (pooled) site, treatment, visit, baseline, and the interaction of visit by treatment and baseline by visit | 0.189 | Difference in LS Means | -1.28 | 2-Sided | 95 | -3.20 | 0.63 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| ANCOVA |
Model included terms of (pooled) site, treatment and baseline |
| <0.001 |
| Difference in LS Means |
| 6.95 |
| 2-Sided |
| 95 |
| 4.22 |
| 9.68 |
Estimate is asenapine versus placebo |
| Superiority or Other (legacy) |
| ANCOVA | Model included terms of (pooled) site, treatment and baseline | <0.001 | Difference in LS Means | 5.11 | 2-Sided | 95 | 2.31 | 7.91 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| ANCOVA |
Model included terms of (pooled) site, treatment and baseline |
| 0.239 |
| Difference in LS Means |
| 1.35 |
| 2-Sided |
| 95 |
| -0.90 |
| 3.59 |
Estimate is asenapine versus placebo |
| Superiority or Other (legacy) |
| ANCOVA | Model included terms of (pooled) site, treatment and baseline | 0.018 | Difference in LS Means | 2.78 | 2-Sided | 95 | 0.48 | 5.08 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |
| ANCOVA |
Model included terms of (pooled) site, treatment and baseline |
| 0.135 |
| Difference in LS Means |
| 0.18 |
| 2-Sided |
| 95 |
| -0.06 |
| 0.41 |
Estimate is asenapine versus placebo |
| Superiority or Other (legacy) |
| ANCOVA | Model included terms of (pooled) site, treatment and baseline | 0.044 | Difference in LS Means | 0.25 | 2-Sided | 95 | 0.01 | 0.49 | Estimate is asenapine versus placebo | Superiority or Other (legacy) |