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| ID | Type | Description | Link |
|---|---|---|---|
| 132324 | Registry Identifier | JAPIC-CTI |
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| Name | Class |
|---|---|
| Meiji Seika Pharma Co., Ltd. | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Asenapine 5 mg BID | Experimental | Participants continue in the same arm they were on in core trial P06124 (except placebo arm starts 5 mg BID at Week 2) and will be re-randomized after Week 6 to asenapine 5 mg BID or asenapine 10 mg BID, administered open-label for 46 weeks. Open label dose can be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability |
|
| Asenapine 10 mg BID | Experimental | Participants continue in the same arm they were on in core trial P06124 (except placebo arm starts 5 mg bid at Week 2) and will be re-randomized after Week 6 to asenapine 5 mg BID or asenapine 10 mg BID, administered open-label for 46 weeks. Open label dose can be adjusted using dose options of 5 and 10 mg BID for efficacy and tolerability |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Asenapine | Drug | Asenapine 5 mg sublingual tablet BID, Asenapine 10 mg sublingual tablet BID |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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). | 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). | Study P06125 baseline and Week 52 |
| Number of Participants With Extrapyramidal Symptoms |
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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 |
|---|---|---|---|
| 37232002 | Derived | Kinoshita T, Takekita Y, Hiraoka S, Tamura F, Iwama Y. Long-term safety and efficacy of sublingual asenapine for the treatment of schizophrenia: A phase III extension study with follow-up for 52 weeks (P06125)-Secondary publication. Neuropsychopharmacol Rep. 2023 Sep;43(3):328-337. doi: 10.1002/npr2.12342. Epub 2023 May 25. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo/Asenapine | Participants in this group had received double-blind placebo BID in preceding study P06124 (NCT01098110), 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| 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 | 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. | 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 | Posted | Number | percentage of participants in category | Study P06124 baseline and P06125 study from Day 1 up to Week 52 |
|
Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
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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/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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastritis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 17.1 | 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 |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C522667 | asenapine |
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| Placebo | Drug | Placebo sublingual tablet BID (first 2 weeks, participants who were in placebo arm of P06124 study only) |
|
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. |
| 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. | 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. | 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. | 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. | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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). | 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. | 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). | 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. | 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. | 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. | 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. | P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52 |
| Lack of Efficacy |
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| Lost to Follow-up |
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| Other reason (not specified) |
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| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| OG001 | 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 |
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| 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. | 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 | Posted | Number | percentage of participants in category | Study P06125 baseline up to Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | kg/m^2 | Study P06124 baseline and study P06125 Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | kg/m^2 | Study P06125 baseline and Week 52 |
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| 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. | All participants randomized in study P06125 who received at least one dose of study drug | Posted | Number | participants | Up to 30 days after last dose of study drug (Up to approximately 56 weeks) |
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| 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. | 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 | Posted | Mean | Standard Deviation | score on a scale | Study P06124 baseline and P06125 study from Day 1 up to Week 52 |
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| 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. | 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 | Posted | Mean | Standard Deviation | score on a scale | Study P06125 baseline up to Week 52 |
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| 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. | 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 | Posted | Mean | Standard Deviation | score on a scale | Study P06124 baseline and P06125 study from Day 1 up to Week 52 |
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| 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. | 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 | Posted | Mean | Standard Deviation | score on a scale | Study P06125 baseline up to Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | percentage of HbA1c | Study P06124 baseline and study P06125 Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | percentage of HbA1c | Study P06125 baseline and Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | mmol/L | Study P06124 baseline and study P06125 Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | mmol/L | Study P06125 baseline and Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | μIU/mL | Study P06124 baseline and study P06125 Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | μIU/mL | Study P06125 baseline and Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | μg/L | Study P06124 baseline and study P06125 Week 52 |
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| 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). | 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 | Posted | Mean | Standard Deviation | μg/L | Study P06125 baseline and Week 52 |
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| 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. | All participants randomized in study P06125 who received at least one dose of study drug | Posted | Number | participants | Up to 30 days after last dose of study drug (Up to approximately 56 weeks) |
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| 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). | All participants randomized in study P06125 who received at least one dose of study drug | Posted | Number | participants | Up to 30 days after last dose of study drug (Up to approximately 56 weeks) |
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| 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. | All participants randomized in study P06125 who received at least one dose of study drug | Posted | Number | percentage of participants | Study P06124 baseline and P06125 study baseline and Week 52 |
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| 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. | All participants randomized in study P06125 who received at least one dose of study drug | Posted | Number | participants | P06125 study from Day 1 up to Week 52 |
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| 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. | 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 | Posted | Median | 95% Confidence Interval | days | P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52 |
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| 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. | 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 | Posted | Median | 95% Confidence Interval | days | P06124 study baseline and Day 42, and P06125 study from Day 1 up to Week 52 |
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| 5 |
| 44 |
| 34 |
| 44 |
| EG001 | 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 | 32 | 157 | 98 | 157 |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
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| Polydipsia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
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| Water intoxication | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
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| Muscle rigidity | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.1 | Systematic Assessment |
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| Neuroleptic malignant syndrome | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Abnormal behaviour | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Completed suicide | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Depressed mood | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Panic attack | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Restlessness | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Schizophrenia | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Stress | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Aalanine aminotranferase increased | Investigations | MedDRA 17.1 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA 17.1 | Systematic Assessment |
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| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 17.1 | Systematic Assessment |
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| Akathisia | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Schizophrenia | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
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| Dysmenorrhea | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.1 | 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.
| Decrease ≥7% |
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| Akathisia |
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| Bradykinesia |
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| Dyskinesia |
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| Dystonia |
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| Extrapyramidal disorder |
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| Parkinsonism |
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| Tardive dyskinesia |
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| Tremor |
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| Parkinsonian gait |
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| Oromandibular dystonia |
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| Blepharospasm |
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| Oculogyric crisis |
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| Muscle rigidity |
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| Muscle tightness |
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| Musculoskeletal stiffness |
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| Gait disturbance |
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| Week 52 (N = 14, 70) |
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| Biperiden hydrochloride |
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| Procyclidine |
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| Trihexyphenidyl |
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| Trihexyphenidyl hydrochloride |
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| Benzatropine mesilate |
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