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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
201
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
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
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
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
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)
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
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
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
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
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
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
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
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
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
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
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
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
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)
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)
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
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
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
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
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