Schizophrenia
Conditions
Brief summary
This is a multi-site, randomized fixed-flexible dose long-term study of asenapine in participants with schizophrenia. The first six weeks of the study will be double-blind and the remainder of the study will be open label. Participants in this study consist of participants who have completed the preceding short-term study (P06124 \[NCT01098110\]), who meet the inclusion criteria and wish to continue receiving study drug, and whom the investigators have deemed eligible for study participation. Participants who were on placebo twice daily (BID) in core trial P06124 will get placebo for the first 2 weeks then 5 mg asenapine BID for the next 4 weeks of double blind treatment, and will be re-randomized after week 6 to asenapine 5 mg BID or asenapine 10 mg BID. Participants who were on asenapine 5 mg BID in core trial P06124 will be re-randomized after Week 6 to asenapine 5 mg BID or asenapine 10 mg BID. Participants who were on asenapine 10 mg BID in core trial P06124 will be re-randomized after Week 6 to asenapine 5 mg BID or asenapine 10 mg BID. After re-randomization, drug will be administered open-label for 46 weeks. During this period dose is flexible can be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability.
Interventions
DRUGAsenapine
Asenapine 5 mg sublingual tablet BID, Asenapine 10 mg sublingual tablet BID
DRUGPlacebo
Placebo sublingual tablet BID (first 2 weeks, participants who were in placebo arm of P06124 study only)
Sponsors
Meiji Seika Pharma Co., Ltd.
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Participant has completed 42-day drug administration in the preceding short-term study (Protocol P06124), has exhibited efficacy (CGI-I at the completion of the preceding short-term study of markedly improved, moderately improved, or slightly improved), has no significant safety problems, and has been judged appropriate for study participation by the investigator. * Male and female participants. Women who are of childbearing potential (i.e., not surgically sterile or post menopausal for at least 1 year) must use medically acceptable birth control. Medically acceptable birth control includes condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, insert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptives, and surgical sterilization (eg, hysterectomy or tubal ligation). Male participants must agree to use condoms during their participation in the study. * Participant must have been explained the nature of the study by the investigator, and be able to provide written consent prior to the conduct of the tests/observation of the clinical study.
Exclusion criteria
* A participant must not have any clinically significant abnormal laboratory, vital sign, physical examination, or electrocardiogram (ECG) findings that, in the investigator's opinion, preclude the participant's participation in the study * A participant must not have a positive pregnancy test or be planning to become pregnant during the term of the study; * A participant must not receive antipsychotics, antidepressants, mood stabilizers, anti-epileptics, monoamine oxidase inhibitors, St. John's Wort, antiemetics that are dopamine antagonist, or traditional herbal medication for psychiatric symptoms at the baseline; * A participant must not be at risk of harming themselves or others, in the investigator's opinion; * A participant must not have been determined to be unsuitable by an investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment | Study P06124 baseline and P06125 study from Day 1 up to Week 52 | For each participant, change in weight from preceding 6-week double-blind Study P06124 baseline to the final assessment of extension study P06125 was determined (calculated as final assessment value minus baseline value). Final assessment was last evaluation of participant in study, whether participant completed or did not complete study. Participants were allocated to categories of percentage change from defined baseline to final assessment. |
| Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment | Study P06125 baseline up to Week 52 | For each participant, change in weight from extension study P06125 baseline to the final assessment of extension study was determined (calculated as final assessment value minus baseline value). Final assessment was last evaluation of participant in study, whether participant completed or did not complete study. Participants were allocated to categories of percentage change from defined baseline to final assessment. |
| Change From Study P06124 Baseline in Body Mass Index (BMI) at Week 52 | Study P06124 baseline and study P06125 Week 52 | For each participant, change in BMI from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value). |
| Change From Study P06125 Baseline in BMI at Week 52 | Study P06125 baseline and Week 52 | For each participant, change in BMI from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value). |
| Number of Participants With Extrapyramidal Symptoms | Up to 30 days after last dose of study drug (Up to approximately 56 weeks) | This measure reports the overall number of participants with any of a group of adverse events that were defined to represent extrapyramidal symptoms. The number of participants with each of the individual adverse events within this definition is also presented, for terms that occurred in at least one participant. For this measure, all adverse event terms within the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Query (SMQ) for extrapyramidal syndrome were treated as extrapyramidal symptoms. |
| Change From Study P06125 Baseline in Insulin at Week 52 | Study P06125 baseline and Week 52 | For each participant, change in insulin from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value). |
| Change From Study P06124 Baseline in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score at Endpoint | Study P06124 baseline and P06125 study from Day 1 up to Week 52 | Change in DIEPSS Total Score from preceding 6-week double-blind Study P06124 baseline to endpoint assessment of extension study P06125 was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Items 1 through 8 are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Each item is rated from 0 (none, normal) to 4 (severe). The Total Score is the sum of scores on Items 1 through 8, with a range from 0 (normal) to 32 (severe). Negative values of change from baseline represent improvement in symptoms. |
| Change From Study P06125 Baseline in DIEPSS Total Score at Endpoint | Study P06125 baseline up to Week 52 | Change in DIEPSS Total Score from extension study P06125 baseline to the endpoint assessment of extension study was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Items 1 through 8 are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Each item is rated from 0 (none, normal) to 4 (severe). The Total Score is the sum of scores on Items 1 through 8, with a range from 0 (normal) to 32 (severe). Negative values of change from baseline represent improvement in symptoms. |
| Change From Study P06124 Baseline in DIEPSS Item 9 Score at Endpoint | Study P06124 baseline and P06125 study from Day 1 up to Week 52 | Change in DIEPSS Item 9 (Global) Score from preceding 6-week double-blind Study P06124 baseline to endpoint assessment of extension study P06125 was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Each item is rated from 0 (none, normal) to 4 (severe). Negative values of change from baseline represent improvement in symptoms. |
| Change From Study P06125 Baseline in DIEPSS Item 9 Score at Endpoint | Study P06125 baseline up to Week 52 | Change in DIEPSS Item 9 (Global) Score from extension study P06125 baseline to the endpoint assessment of extension study was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Each item is rated from 0 (none, normal) to 4 (severe). Negative values of change from baseline represent improvement in symptoms. |
| Change From Study P06124 Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52 | Study P06124 baseline and study P06125 Week 52 | For each participant, change in HbA1c from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value). |
| Change From Study P06125 Baseline in HbA1c at Week 52 | Study P06125 baseline and Week 52 | For each participant, change in HbA1c from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value). |
| Change From Study P06124 Baseline in Fasting Glucose at Week 52 | Study P06124 baseline and study P06125 Week 52 | For each participant, change in fasting glucose from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value). |
| Change From Study P06125 Baseline in Fasting Glucose at Week 52 | Study P06125 baseline and Week 52 | For each participant, change in fasting glucose from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value). |
| Change From Study P06124 Baseline in Insulin at Week 52 | Study P06124 baseline and study P06125 Week 52 | For each participant, change in insulin from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value). |
| Change From Study P06124 Baseline in Prolactin at Week 52 | Study P06124 baseline and study P06125 Week 52 | For each participant, change in prolactin from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value). |
| Change From Study P06125 Baseline in Prolactin at Week 52 | Study P06125 baseline and Week 52 | For each participant, change in prolactin from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value). |
| Number of Participants With Serious Adverse Events (AEs) | Up to 30 days after last dose of study drug (Up to approximately 56 weeks) | An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with study drug administration, whether or not considered related to study drug. A serious AE (SAE) is any AE occurring at any dose that results in death, is life-threatening, results in hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. In addition, an important medical event that may not result in death, be life-threatening, or require hospitalization may be considered an SAE when it may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. |
| Number of Participants With Non-serious AEs | Up to 30 days after last dose of study drug (Up to approximately 56 weeks) | An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with study drug administration, whether or not considered related to study drug. This measure presents the number of participants with at least one AEs that was non-serious (i.e., was not determined to be an SAE). |
| Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 | Study P06124 baseline and P06125 study baseline and Week 52 | The percentage of participants with abnormal ECG findings is reported for three time points: 6-week double-blind study P06124 baseline, extension study P06125 baseline and extension study Week 52. |
| Number of Participants Who Took Antiparkinsonian Drugs | P06125 study from Day 1 up to Week 52 | This measure presents the number of participants who used antiparkinsonian drugs started on or after the start of study treatment in extension study P06125. Antiparkinsonian drugs were defined as those categorized into the N04 code (antiparkinson drugs) of the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) classification system. |
| Median Time to Loss of Effect in Responders | P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52 | Median time to loss of effect from P06125 extension study baseline was estimated using Kaplan-Meier product-limit method. Result reported in Responders, participants with ≥30% decrease from study P06124 baseline in Positive and Negative Syndrome Scale (PANSS, schizophrenia symptom scale) Total Score at the end of study P06124. Investigator or subinvestigator was to determine whether the study drug failed to maintain effect based on occurrence of any of the following: 1) Increase in PANSS Total Score ≥30% from P06125 extension study baseline, 2) Determination that participant's schizophrenic symptomatology had deteriorated requiring one or more of defined interventions (add new antipsychotic drug, increase in level of psychiatric outpatient care, or hospitalization/increase in level of hospitalization for psychiatric need), 3) Clinical Global Impression-Severity (CGI-S) score ≥6, 4) Discontinuation from study because of lack of efficacy, 5) AE/SAE of worsening of schizophrenia. |
| Median Time to Loss of Effect in Non-Responders | P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52 | Median time to loss of effect from P06125 extension study baseline was estimated using Kaplan-Meier product-limit method. Result reported in Non-Responders, participants without ≥30% decrease from study P06124 baseline in PANSS Total Score at the end of study P06124. Investigator or subinvestigator was to determine whether the study drug failed to maintain effect based on occurrence of any of the following: 1) Increase in PANSS Total Score ≥30% from P06125 extension study baseline, 2) Determination that participant's schizophrenic symptomatology had deteriorated requiring one or more of defined interventions (add new antipsychotic drug, increase in level of psychiatric outpatient care, or hospitalization/increase in level of hospitalization for psychiatric need), 3) Clinical Global Impression-Severity (CGI-S) score ≥6, 4) Discontinuation from study because of lack of efficacy, 5) AE/SAE of worsening of schizophrenia. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Asenapine Participants in this group had received double-blind placebo BID in preceding study P06124, and continued on same double-blind dose for first 2 weeks of extension study P06125, then took double-blind asenapine 5 mg BID for 4 weeks, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability | 44 |
| Asenapine 5/10 mg BID Participants in this group had received double-blind asenapine 5 or 10 mg BID in preceding study P06124, and continued on same double-blind dose for first 6 weeks of extension study P06125, after which were re-randomized to open label asenapine 5 or 10 mg BID for 46 weeks. Open label dose could be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability | 157 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 35 |
| Overall Study | Lack of Efficacy | 5 | 9 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Other reason (not specified) | 5 | 4 |
| Overall Study | Withdrawal by Subject | 9 | 35 |
Baseline characteristics
| Characteristic | Asenapine 5/10 mg BID | Total | Placebo/Asenapine |
|---|---|---|---|
| Age, Continuous | 41.82 years STANDARD_DEVIATION 11.44 | 41.97 years STANDARD_DEVIATION 11.86 | 42.50 years STANDARD_DEVIATION 13.39 |
| Sex: Female, Male Female | 79 Participants | 105 Participants | 26 Participants |
| Sex: Female, Male Male | 78 Participants | 96 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 44 | 98 / 157 |
| serious Total, serious adverse events | 5 / 44 | 32 / 157 |
Outcome results
Primary
Change From Study P06124 Baseline in Body Mass Index (BMI) at Week 52
For each participant, change in BMI from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06124 baseline and study P06125 Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06124 Baseline in Body Mass Index (BMI) at Week 52 | -0.04 kg/m^2 | Standard Deviation 2.83 |
| Asenapine 5/10 mg BID | Change From Study P06124 Baseline in Body Mass Index (BMI) at Week 52 | 0.91 kg/m^2 | Standard Deviation 2.74 |
Primary
Change From Study P06124 Baseline in DIEPSS Item 9 Score at Endpoint
Change in DIEPSS Item 9 (Global) Score from preceding 6-week double-blind Study P06124 baseline to endpoint assessment of extension study P06125 was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Each item is rated from 0 (none, normal) to 4 (severe). Negative values of change from baseline represent improvement in symptoms.
Time frame: Study P06124 baseline and P06125 study from Day 1 up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06124 Baseline in DIEPSS Item 9 Score at Endpoint | 0.14 score on a scale | Standard Deviation 0.63 |
| Asenapine 5/10 mg BID | Change From Study P06124 Baseline in DIEPSS Item 9 Score at Endpoint | -0.01 score on a scale | Standard Deviation 0.73 |
Primary
Change From Study P06124 Baseline in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score at Endpoint
Change in DIEPSS Total Score from preceding 6-week double-blind Study P06124 baseline to endpoint assessment of extension study P06125 was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Items 1 through 8 are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Each item is rated from 0 (none, normal) to 4 (severe). The Total Score is the sum of scores on Items 1 through 8, with a range from 0 (normal) to 32 (severe). Negative values of change from baseline represent improvement in symptoms.
Time frame: Study P06124 baseline and P06125 study from Day 1 up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06124 Baseline in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score at Endpoint | -0.11 score on a scale | Standard Deviation 1.99 |
| Asenapine 5/10 mg BID | Change From Study P06124 Baseline in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score at Endpoint | -0.46 score on a scale | Standard Deviation 2.54 |
Primary
Change From Study P06124 Baseline in Fasting Glucose at Week 52
For each participant, change in fasting glucose from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06124 baseline and study P06125 Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06124 Baseline in Fasting Glucose at Week 52 | 0.37 mmol/L | Standard Deviation 1 |
| Asenapine 5/10 mg BID | Change From Study P06124 Baseline in Fasting Glucose at Week 52 | 0.28 mmol/L | Standard Deviation 1.93 |
Primary
Change From Study P06124 Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52
For each participant, change in HbA1c from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06124 baseline and study P06125 Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06124 Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52 | -0.09 percentage of HbA1c | Standard Deviation 0.44 |
| Asenapine 5/10 mg BID | Change From Study P06124 Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52 | -0.02 percentage of HbA1c | Standard Deviation 0.82 |
Primary
Change From Study P06124 Baseline in Insulin at Week 52
For each participant, change in insulin from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06124 baseline and study P06125 Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06124 Baseline in Insulin at Week 52 | 4.06 μIU/mL | Standard Deviation 16.27 |
| Asenapine 5/10 mg BID | Change From Study P06124 Baseline in Insulin at Week 52 | 2.24 μIU/mL | Standard Deviation 16.06 |
Primary
Change From Study P06124 Baseline in Prolactin at Week 52
For each participant, change in prolactin from preceding 6-week double-blind Study P06124 baseline to Week 52 of extension study P06125 was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06124 baseline and study P06125 Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06124 Baseline in Prolactin at Week 52 | -37.46 μg/L | Standard Deviation 68.83 |
| Asenapine 5/10 mg BID | Change From Study P06124 Baseline in Prolactin at Week 52 | -20.98 μg/L | Standard Deviation 47.14 |
Primary
Change From Study P06125 Baseline in BMI at Week 52
For each participant, change in BMI from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06125 baseline and Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06125 Baseline in BMI at Week 52 | 0.35 kg/m^2 | Standard Deviation 2.48 |
| Asenapine 5/10 mg BID | Change From Study P06125 Baseline in BMI at Week 52 | 0.75 kg/m^2 | Standard Deviation 2.41 |
Primary
Change From Study P06125 Baseline in DIEPSS Item 9 Score at Endpoint
Change in DIEPSS Item 9 (Global) Score from extension study P06125 baseline to the endpoint assessment of extension study was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Each item is rated from 0 (none, normal) to 4 (severe). Negative values of change from baseline represent improvement in symptoms.
Time frame: Study P06125 baseline up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06125 Baseline in DIEPSS Item 9 Score at Endpoint | 0.18 score on a scale | Standard Deviation 0.69 |
| Asenapine 5/10 mg BID | Change From Study P06125 Baseline in DIEPSS Item 9 Score at Endpoint | -0.02 score on a scale | Standard Deviation 0.62 |
Primary
Change From Study P06125 Baseline in DIEPSS Total Score at Endpoint
Change in DIEPSS Total Score from extension study P06125 baseline to the endpoint assessment of extension study was determined (calculated as endpoint value minus baseline value). Endpoint assessment was last evaluation of participant for this measure in study, whether participant completed or did not complete study. DIEPSS is a scale, rated by the investigator or rater appointed by the investigator, used to evaluate the severity of drug induced extrapyramidal symptoms occurring during antipsychotic drug treatment. It consists of 9 items: Items 1 through 8 assess individual symptoms; Item 9 is an assessment of global severity. Items 1 through 8 are classified into 4 categories of parkinsonism, akathisia, dystonia and dyskinesia. Each item is rated from 0 (none, normal) to 4 (severe). The Total Score is the sum of scores on Items 1 through 8, with a range from 0 (normal) to 32 (severe). Negative values of change from baseline represent improvement in symptoms.
Time frame: Study P06125 baseline up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and endpoint assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06125 Baseline in DIEPSS Total Score at Endpoint | 0.25 score on a scale | Standard Deviation 1.57 |
| Asenapine 5/10 mg BID | Change From Study P06125 Baseline in DIEPSS Total Score at Endpoint | -0.03 score on a scale | Standard Deviation 1.9 |
Primary
Change From Study P06125 Baseline in Fasting Glucose at Week 52
For each participant, change in fasting glucose from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06125 baseline and Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06125 Baseline in Fasting Glucose at Week 52 | 0.60 mmol/L | Standard Deviation 1.79 |
| Asenapine 5/10 mg BID | Change From Study P06125 Baseline in Fasting Glucose at Week 52 | 0.00 mmol/L | Standard Deviation 2.16 |
Primary
Change From Study P06125 Baseline in HbA1c at Week 52
For each participant, change in HbA1c from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06125 baseline and Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06125 Baseline in HbA1c at Week 52 | 0.21 percentage of HbA1c | Standard Deviation 0.36 |
| Asenapine 5/10 mg BID | Change From Study P06125 Baseline in HbA1c at Week 52 | 0.12 percentage of HbA1c | Standard Deviation 1.02 |
Primary
Change From Study P06125 Baseline in Insulin at Week 52
For each participant, change in insulin from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06125 baseline and Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06125 Baseline in Insulin at Week 52 | -5.61 μIU/mL | Standard Deviation 28.89 |
| Asenapine 5/10 mg BID | Change From Study P06125 Baseline in Insulin at Week 52 | 0.56 μIU/mL | Standard Deviation 17.88 |
Primary
Change From Study P06125 Baseline in Prolactin at Week 52
For each participant, change in prolactin from extension study P06125 baseline to Week 52 of extension study was determined (calculated as Week 52 value minus baseline value).
Time frame: Study P06125 baseline and Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo/Asenapine | Change From Study P06125 Baseline in Prolactin at Week 52 | 10.91 μg/L | Standard Deviation 20.58 |
| Asenapine 5/10 mg BID | Change From Study P06125 Baseline in Prolactin at Week 52 | -1.59 μg/L | Standard Deviation 17.22 |
Primary
Median Time to Loss of Effect in Non-Responders
Median time to loss of effect from P06125 extension study baseline was estimated using Kaplan-Meier product-limit method. Result reported in Non-Responders, participants without ≥30% decrease from study P06124 baseline in PANSS Total Score at the end of study P06124. Investigator or subinvestigator was to determine whether the study drug failed to maintain effect based on occurrence of any of the following: 1) Increase in PANSS Total Score ≥30% from P06125 extension study baseline, 2) Determination that participant's schizophrenic symptomatology had deteriorated requiring one or more of defined interventions (add new antipsychotic drug, increase in level of psychiatric outpatient care, or hospitalization/increase in level of hospitalization for psychiatric need), 3) Clinical Global Impression-Severity (CGI-S) score ≥6, 4) Discontinuation from study because of lack of efficacy, 5) AE/SAE of worsening of schizophrenia.
Time frame: P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, had PANSS measurement at P06125 baseline and at least one post-baseline PANSS measurement, and were study P06124 Non-Responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/Asenapine | Median Time to Loss of Effect in Non-Responders | 53.0 days |
| Asenapine 5/10 mg BID | Median Time to Loss of Effect in Non-Responders | 368.0 days |
Primary
Median Time to Loss of Effect in Responders
Median time to loss of effect from P06125 extension study baseline was estimated using Kaplan-Meier product-limit method. Result reported in Responders, participants with ≥30% decrease from study P06124 baseline in Positive and Negative Syndrome Scale (PANSS, schizophrenia symptom scale) Total Score at the end of study P06124. Investigator or subinvestigator was to determine whether the study drug failed to maintain effect based on occurrence of any of the following: 1) Increase in PANSS Total Score ≥30% from P06125 extension study baseline, 2) Determination that participant's schizophrenic symptomatology had deteriorated requiring one or more of defined interventions (add new antipsychotic drug, increase in level of psychiatric outpatient care, or hospitalization/increase in level of hospitalization for psychiatric need), 3) Clinical Global Impression-Severity (CGI-S) score ≥6, 4) Discontinuation from study because of lack of efficacy, 5) AE/SAE of worsening of schizophrenia.
Time frame: P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, had PANSS measurement at P06125 baseline and at least one post-baseline PANSS measurement, and were study P06124 Responders
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo/Asenapine | Median Time to Loss of Effect in Responders | 357.0 days |
| Asenapine 5/10 mg BID | Median Time to Loss of Effect in Responders | 177.0 days |
Primary
Number of Participants Who Took Antiparkinsonian Drugs
This measure presents the number of participants who used antiparkinsonian drugs started on or after the start of study treatment in extension study P06125. Antiparkinsonian drugs were defined as those categorized into the N04 code (antiparkinson drugs) of the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) classification system.
Time frame: P06125 study from Day 1 up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo/Asenapine | Number of Participants Who Took Antiparkinsonian Drugs | Biperiden hydrochloride | 3 participants |
| Placebo/Asenapine | Number of Participants Who Took Antiparkinsonian Drugs | Trihexyphenidyl | 0 participants |
| Placebo/Asenapine | Number of Participants Who Took Antiparkinsonian Drugs | Biperiden | 4 participants |
| Placebo/Asenapine | Number of Participants Who Took Antiparkinsonian Drugs | Trihexyphenidyl hydrochloride | 1 participants |
| Placebo/Asenapine | Number of Participants Who Took Antiparkinsonian Drugs | Procyclidine | 2 participants |
| Placebo/Asenapine | Number of Participants Who Took Antiparkinsonian Drugs | Benzatropine mesilate | 4 participants |
| Placebo/Asenapine | Number of Participants Who Took Antiparkinsonian Drugs | Any antiparkinsonian drug | 12 participants |
| Asenapine 5/10 mg BID | Number of Participants Who Took Antiparkinsonian Drugs | Benzatropine mesilate | 5 participants |
| Asenapine 5/10 mg BID | Number of Participants Who Took Antiparkinsonian Drugs | Any antiparkinsonian drug | 40 participants |
| Asenapine 5/10 mg BID | Number of Participants Who Took Antiparkinsonian Drugs | Biperiden | 8 participants |
| Asenapine 5/10 mg BID | Number of Participants Who Took Antiparkinsonian Drugs | Biperiden hydrochloride | 16 participants |
| Asenapine 5/10 mg BID | Number of Participants Who Took Antiparkinsonian Drugs | Procyclidine | 1 participants |
| Asenapine 5/10 mg BID | Number of Participants Who Took Antiparkinsonian Drugs | Trihexyphenidyl | 3 participants |
| Asenapine 5/10 mg BID | Number of Participants Who Took Antiparkinsonian Drugs | Trihexyphenidyl hydrochloride | 7 participants |
Primary
Number of Participants With Extrapyramidal Symptoms
This measure reports the overall number of participants with any of a group of adverse events that were defined to represent extrapyramidal symptoms. The number of participants with each of the individual adverse events within this definition is also presented, for terms that occurred in at least one participant. For this measure, all adverse event terms within the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Query (SMQ) for extrapyramidal syndrome were treated as extrapyramidal symptoms.
Time frame: Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Population: All participants randomized in study P06125 who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Any extrapyramidal symptom | 11 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Restlessness | 1 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Akathisia | 2 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Bradykinesia | 0 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Dyskinesia | 2 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Dystonia | 0 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Extrapyramidal disorder | 2 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Parkinsonism | 0 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Tardive dyskinesia | 0 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Tremor | 4 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Parkinsonian gait | 1 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Oromandibular dystonia | 1 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Blepharospasm | 1 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Oculogyric crisis | 0 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Muscle rigidity | 2 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Muscle tightness | 0 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Musculoskeletal stiffness | 1 participants |
| Placebo/Asenapine | Number of Participants With Extrapyramidal Symptoms | Gait disturbance | 0 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Oculogyric crisis | 1 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Any extrapyramidal symptom | 34 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Tremor | 6 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Restlessness | 2 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Gait disturbance | 1 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Akathisia | 13 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Parkinsonian gait | 0 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Bradykinesia | 2 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Muscle rigidity | 1 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Dyskinesia | 3 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Oromandibular dystonia | 0 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Dystonia | 2 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Musculoskeletal stiffness | 2 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Extrapyramidal disorder | 6 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Blepharospasm | 0 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Parkinsonism | 1 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Muscle tightness | 1 participants |
| Asenapine 5/10 mg BID | Number of Participants With Extrapyramidal Symptoms | Tardive dyskinesia | 1 participants |
Primary
Number of Participants With Non-serious AEs
An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with study drug administration, whether or not considered related to study drug. This measure presents the number of participants with at least one AEs that was non-serious (i.e., was not determined to be an SAE).
Time frame: Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Population: All participants randomized in study P06125 who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Asenapine | Number of Participants With Non-serious AEs | 40 participants |
| Asenapine 5/10 mg BID | Number of Participants With Non-serious AEs | 131 participants |
Primary
Number of Participants With Serious Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with study drug administration, whether or not considered related to study drug. A serious AE (SAE) is any AE occurring at any dose that results in death, is life-threatening, results in hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. In addition, an important medical event that may not result in death, be life-threatening, or require hospitalization may be considered an SAE when it may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time frame: Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Population: All participants randomized in study P06125 who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Asenapine | Number of Participants With Serious Adverse Events (AEs) | 5 participants |
| Asenapine 5/10 mg BID | Number of Participants With Serious Adverse Events (AEs) | 32 participants |
Primary
Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment
For each participant, change in weight from preceding 6-week double-blind Study P06124 baseline to the final assessment of extension study P06125 was determined (calculated as final assessment value minus baseline value). Final assessment was last evaluation of participant in study, whether participant completed or did not complete study. Participants were allocated to categories of percentage change from defined baseline to final assessment.
Time frame: Study P06124 baseline and P06125 study from Day 1 up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06124 baseline and study P06125 final assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo/Asenapine | Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment | Increase ≥7% | 12.9 percentage of participants in category |
| Placebo/Asenapine | Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment | Change within ± 7% | 64.5 percentage of participants in category |
| Placebo/Asenapine | Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment | Decrease ≥7% | 22.6 percentage of participants in category |
| Asenapine 5/10 mg BID | Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment | Increase ≥7% | 26.8 percentage of participants in category |
| Asenapine 5/10 mg BID | Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment | Change within ± 7% | 61.6 percentage of participants in category |
| Asenapine 5/10 mg BID | Percentage of Participants in Categories of Change in Weight From Study P06124 Baseline to Final Assessment | Decrease ≥7% | 11.6 percentage of participants in category |
Primary
Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment
For each participant, change in weight from extension study P06125 baseline to the final assessment of extension study was determined (calculated as final assessment value minus baseline value). Final assessment was last evaluation of participant in study, whether participant completed or did not complete study. Participants were allocated to categories of percentage change from defined baseline to final assessment.
Time frame: Study P06125 baseline up to Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug, and had data for measure at study P06125 baseline and final assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo/Asenapine | Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment | Increase ≥7% | 22.6 percentage of participants in category |
| Placebo/Asenapine | Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment | Change within ± 7% | 64.5 percentage of participants in category |
| Placebo/Asenapine | Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment | Decrease ≥7% | 12.9 percentage of participants in category |
| Asenapine 5/10 mg BID | Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment | Increase ≥7% | 23.9 percentage of participants in category |
| Asenapine 5/10 mg BID | Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment | Change within ± 7% | 62.3 percentage of participants in category |
| Asenapine 5/10 mg BID | Percentage of Participants in Categories of Change in Weight From Study P06125 Baseline to Final Assessment | Decrease ≥7% | 13.8 percentage of participants in category |
Primary
Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52
The percentage of participants with abnormal ECG findings is reported for three time points: 6-week double-blind study P06124 baseline, extension study P06125 baseline and extension study Week 52.
Time frame: Study P06124 baseline and P06125 study baseline and Week 52
Population: All participants randomized in study P06125 who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo/Asenapine | Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 | P06124 baseline (N = 43, 153) | 41.9 percentage of participants |
| Placebo/Asenapine | Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 | P06125 baseline (N = 44, 156) | 34.1 percentage of participants |
| Placebo/Asenapine | Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 | Week 52 (N = 14, 70) | 42.9 percentage of participants |
| Asenapine 5/10 mg BID | Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 | P06124 baseline (N = 43, 153) | 24.8 percentage of participants |
| Asenapine 5/10 mg BID | Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 | P06125 baseline (N = 44, 156) | 26.9 percentage of participants |
| Asenapine 5/10 mg BID | Percentage of Participants With Abnormalities on Electrocardiogram (ECG) at Study P06124 Baseline, Study P06125 Baseline and Week 52 | Week 52 (N = 14, 70) | 25.7 percentage of participants |