Schizophrenia
Conditions
Brief summary
This is a multi-site, open-label fixed-flexible dose long-term study of asenapine in participants with schizophrenia. Participants in this study consist of schizophrenia with residual subtype or receiving high dose/multiple antipsychotic drugs, treatment refractory, or elderly participants with schizophrenia. The treatment period is up to 52 weeks.
Interventions
DRUGAsenapine
5 mg or 10 mg fast-dissolving sublingual tablets BID for up to 52 weeks
Sponsors
Organon and Co
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Minimum age of 20 years * Participants who meet at least one of the following: * current diagnosis of schizophrenia of residual subtype * received treatment with 3 or more antipsychotic drugs * treatment-refractory participants with schizophrenia * 65 years old and over with positive schizophrenia symptoms with score of 3 (mild) or more in 1 or more items in the positive subscale of the Positive and Negative Syndrome Scale (PANSS) at the baseline * Participants who have a Clinical Global Impressions-Severity (CGI-S) score of at least 4 (moderately ill) at the baseline
Exclusion criteria
* Uncontrolled, unstable clinically significant medical condition * Clinically significant abnormal laboratory, vital sign, physical examination, or electrocardiogram (ECG) findings at Screening * Positive pregnancy test at Screening, or the intention to become pregnant during the course of the study * Seizure disorder beyond childhood (12 years old or younger) * History of neuroleptic malignant syndrome * Allergy or sensitivity to drugs such as psychotropics and antipsychotics * Known history of or currently treated for narrow angle glaucoma * Parkinson's disease * Diagnosis of schizoaffective disorder; schizophreniform disorder * Concurrent psychiatric disorder other than schizophrenia coded on Axis I; a primary diagnosis other than schizophrenia * Diagnosis of borderline personality disorder * Diagnosis of mental retardation or organic brain disorder * Current (past 6 months) substance abuse or dependence according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria (excluding nicotine) * Positive drug/alcohol tests at the Screening visit * Imminent risk of self-harm or harm to others, in the Investigator's opinion * Substance induced psychotic disorder or a behavioral disturbance thought to be due to substance abuse * Currently under involuntary inpatient confinement * Use of a non-approved drug in Japan within 12 weeks prior to informed consent * Previously treated in an asenapine study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weight at Week 52 | Baseline and Week 52 | For each participant, change from baseline in weight was calculated as the Week 52 value minus the baseline value. |
| Change From Baseline in BMI at Week 52 | Baseline and Week 52 | For each participant, change from baseline in BMI was calculated as the Week 52 value minus the 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 Baseline in HbA1c at Week 52 | Baseline and Week 52 | Blood samples for determination of HbA1c were obtained at baseline and during the study. For each participant, change from baseline in HbA1c at Week 52 was calculated as the Week 52 value minus the baseline value. |
| Change From Baseline in Fasting Glucose at Week 52 | Baseline and Week 52 | Blood samples for determination of fasting glucose level were obtained at baseline and during the study. For each participant, change from baseline in fasting glucose at Week 52 was calculated as the Week 52 level minus the baseline level. |
| Change From Baseline in Insulin at Week 52 | Baseline and Week 52 | Blood samples for determination of insulin level were obtained at baseline and during the study. For each participant, change from baseline in insulin at Week 52 was calculated as the Week 52 level minus the baseline level. |
| Change From Baseline in Prolactin at Week 52 | Baseline and Week 52 | Blood samples for determination of prolactin level were obtained at baseline and during the study. For each participant, change from baseline in prolactin at Week 52 was calculated as the Week 52 level minus the baseline level. |
| Change From Baseline in PANSS Total Score at Week 52 | Baseline and Week 52 | The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Week 52 (calculated for a participant as Week 52 value minus baseline value); improvement in symptoms is represented by negative values. |
| Change From Baseline in PANSS Total Score at Final Assessment | Baseline up to Week 52 | The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at the final assessment for a participant (calculated for a participant as final assessment value minus baseline value); improvement in symptoms is represented by negative values. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asenapine All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks. | 157 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 37 |
| Overall Study | Lack of Efficacy | 7 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other reason (not specified) | 1 |
| Overall Study | Withdrawal by Subject | 31 |
Baseline characteristics
| Characteristic | Asenapine |
|---|---|
| Age, Continuous | 56.37 years STANDARD_DEVIATION 14.17 |
| Body Mass index (BMI) | 23.04 kg/m^2 STANDARD_DEVIATION 4.37 |
| Fasting glucose | 5.14 mmol/L STANDARD_DEVIATION 0.74 |
| Hemoglobin A1c (HbA1c) | 5.28 percent STANDARD_DEVIATION 0.47 |
| Insulin | 6.35 µIU/mL STANDARD_DEVIATION 4.73 |
| Positive and Negative Syndrome Scale (PANSS) total score | 89.99 score on a scale STANDARD_DEVIATION 18.31 |
| Prolactin | 43.92 µg/L STANDARD_DEVIATION 41.66 |
| Sex: Female, Male Female | 76 Participants |
| Sex: Female, Male Male | 81 Participants |
| Weight | 59.45 kg STANDARD_DEVIATION 13.76 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 111 / 157 |
| serious Total, serious adverse events | 14 / 157 |
Outcome results
Primary
Change From Baseline in BMI at Week 52
For each participant, change from baseline in BMI was calculated as the Week 52 value minus the baseline value.
Time frame: Baseline and Week 52
Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline in BMI at Week 52 | 0.07 kg/m^2 | Standard Deviation 1.93 |
Primary
Change From Baseline in Fasting Glucose at Week 52
Blood samples for determination of fasting glucose level were obtained at baseline and during the study. For each participant, change from baseline in fasting glucose at Week 52 was calculated as the Week 52 level minus the baseline level.
Time frame: Baseline and Week 52
Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline in Fasting Glucose at Week 52 | 0.11 mmol/L | Standard Deviation 0.63 |
Primary
Change From Baseline in HbA1c at Week 52
Blood samples for determination of HbA1c were obtained at baseline and during the study. For each participant, change from baseline in HbA1c at Week 52 was calculated as the Week 52 value minus the baseline value.
Time frame: Baseline and Week 52
Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline in HbA1c at Week 52 | 0.00 percent | Standard Deviation 0.26 |
Primary
Change From Baseline in Insulin at Week 52
Blood samples for determination of insulin level were obtained at baseline and during the study. For each participant, change from baseline in insulin at Week 52 was calculated as the Week 52 level minus the baseline level.
Time frame: Baseline and Week 52
Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline in Insulin at Week 52 | 2.31 µIU/mL | Standard Deviation 11.93 |
Primary
Change From Baseline in PANSS Total Score at Final Assessment
The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at the final assessment for a participant (calculated for a participant as final assessment value minus baseline value); improvement in symptoms is represented by negative values.
Time frame: Baseline up to Week 52
Population: Participants who received at least one dose of study drug and had a baseline and at least one post-baseline PANSS measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline in PANSS Total Score at Final Assessment | -5.48 score on a scale | Standard Error 1.08 |
Primary
Change From Baseline in PANSS Total Score at Week 52
The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Week 52 (calculated for a participant as Week 52 value minus baseline value); improvement in symptoms is represented by negative values.
Time frame: Baseline and Week 52
Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 PANSS measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline in PANSS Total Score at Week 52 | -11.08 score on a scale | Standard Error 1.36 |
Primary
Change From Baseline in Prolactin at Week 52
Blood samples for determination of prolactin level were obtained at baseline and during the study. For each participant, change from baseline in prolactin at Week 52 was calculated as the Week 52 level minus the baseline level.
Time frame: Baseline and Week 52
Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline in Prolactin at Week 52 | 0.66 µg/L | Standard Deviation 24.2 |
Primary
Change From Baseline in Weight at Week 52
For each participant, change from baseline in weight was calculated as the Week 52 value minus the baseline value.
Time frame: Baseline and Week 52
Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline in Weight at Week 52 | 0.25 kg | Standard Deviation 5.23 |
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: Participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Any extrapyramidal symptom | 24 participants |
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Restlessness | 3 participants |
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Akathisia | 3 participants |
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Dystonia | 2 participants |
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Extrapyramidal disorder | 10 participants |
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Parkinsonism | 1 participants |
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Tremor | 5 participants |
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Oculogyric crisis | 2 participants |
| Asenapine | Number of Participants With Extrapyramidal Symptoms | Gait disturbance | 1 participants |