Schizophrenia
Conditions
Brief summary
This study is designed to evaluate efficacy and safety of HP-3070 compared with placebo transdermal patch in subjects diagnosed with schizophrenia.
Detailed description
This is a Phase 3, randomized, double-blind, placebo-controlled, in-patient, efficacy, and safety study to evaluate HP-3070 for the treatment of schizophrenia. This study is designed to evaluate efficacy and safety of HP-3070 compared with placebo transdermal patch in subjects diagnosed with schizophrenia, who are in an acute exacerbation and to assess the impacts of covariates on asenapine exposure as delivered in a patch formulation, using a population-based approach.
Interventions
DRUGLow Dose Asenapine maleate transdermal patch
The study will evaluate low dose Asenapine maleate transdermal patch
DRUGHigh Dose Asenapine maleate transdermal patch
The study will evaluate high dose Asenapine maleate transdermal patch
DRUGPlacebo
The study will evaluate placebo transdermal patch.
Sponsors
Noven Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Current diagnosis of schizophrenia. * Subject has PANSS total score ≥80, AND score of 4 or more in at least 2 of the following PANSS items at Screening and at Baseline: conceptual disorganization delusions; hallucinatory behavior; unusual thought content. * Subjects must be able to wear a transdermal patch for 24 hours.
Exclusion criteria
* Subject has been diagnosed with schizophrenia less than 6 months prior to Screening Visit. * Subject has received within 90 days of Screening Visit: electroconvulsive therapy; transcranial magnetic stimulation; vagal nerve stimulation; or other brain stimulation treatments * Subject has experienced acute depressive symptoms within 30 days prior to Screening Visit that requires treatment with an antidepressant, as determined by the Investigator. * Currently taking clozapine for the treatment of schizophrenia. * Has hypothyroidism or hyperthyroidism. * Subject is currently being treated with insulin for diabetes. * Subject has epilepsy or history of seizures. * Positive urine pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Syndrome Scale (PANSS) Total Score: Change From Baseline to Week 6. | 6 weeks | To evaluate efficacy and safety of HP-3070 compared with placebo for the treatment of schizophrenia as evaluated by Positive and Negative Syndrome Scale (PANSS) total score. The PANSS total score is the sum of all 30 items (7 positive items, 7 negative items, and 16 general psychopathology items). For each item, severity was rated on an anchored 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. If one or more items are missing at a given assessment, the total score is set to missing. Total score ranges from 30 to 210. Score indicates severity of the disease, i.e. low score = low severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Clinical Global Impression - Severity of Illness Scale: Change From Baseline to Week 6. | 6 weeks | To evaluate efficacy and safety of HP-3070 compared with placebo for the treatment of schizophrenia as evaluated by the Clinical Global Impression - Severity of Illness Scale. The severity of illness for each participant was rated using the CGI-S. The rater or Investigator answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?. Response choices included: 0 = not assessed; 1 = normal, not at all ill, 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Asenapine Maleate Patch Low dose asenapine maleate, transdermal patches will be compared against placebo patches.
Low Dose Asenapine maleate transdermal patch: The study will evaluate low dose Asenapine maleate transdermal patch
Placebo: The study will evaluate placebo transdermal patch. | 204 |
| High Dose Asenapine Maleate Patch High dose asenapine maleate, transdermal patches will be compared against placebo patches.
High Dose Asenapine maleate transdermal patch: The study will evaluate high dose Asenapine maleate transdermal patch
Placebo: The study will evaluate placebo transdermal patch. | 206 |
| Placebo Patch Placebo transdermal patch | 206 |
| Total | 616 |
Baseline characteristics
| Characteristic | Total | Low Dose Asenapine Maleate Patch | High Dose Asenapine Maleate Patch | Placebo Patch |
|---|---|---|---|---|
| Age, Customized <55 | 511 Participants | 168 Participants | 172 Participants | 171 Participants |
| Age, Customized >=55 | 105 Participants | 36 Participants | 34 Participants | 35 Participants |
| BMI | 26.251 kg/m^2 STANDARD_DEVIATION 4.9205 | 26.591 kg/m^2 STANDARD_DEVIATION 5.1151 | 26.240 kg/m^2 STANDARD_DEVIATION 4.7834 | 25.925 kg/m^2 STANDARD_DEVIATION 4.8602 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 10 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 600 Participants | 194 Participants | 201 Participants | 205 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 172.0 cm STANDARD_DEVIATION 9.1 | 172.5 cm STANDARD_DEVIATION 9.08 | 171.8 cm STANDARD_DEVIATION 9.09 | 171.8 cm STANDARD_DEVIATION 9.16 |
| PANSS total score <90 | 152 Participants | 45 Participants | 53 Participants | 54 Participants |
| PANSS total score >=90 | 462 Participants | 159 Participants | 151 Participants | 152 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 146 Participants | 47 Participants | 45 Participants | 54 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 468 Participants | 157 Participants | 159 Participants | 152 Participants |
| Region of Enrollment Bulgaria | 88 participants | 29 participants | 30 participants | 29 participants |
| Region of Enrollment Russia | 180 participants | 60 participants | 60 participants | 60 participants |
| Region of Enrollment Serbia | 57 participants | 19 participants | 19 participants | 19 participants |
| Region of Enrollment Ukraine | 106 participants | 35 participants | 35 participants | 36 participants |
| Region of Enrollment United States | 185 participants | 61 participants | 62 participants | 62 participants |
| Sex: Female, Male Female | 243 Participants | 73 Participants | 95 Participants | 75 Participants |
| Sex: Female, Male Male | 373 Participants | 131 Participants | 111 Participants | 131 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 204 | 0 / 204 | 0 / 206 |
| other Total, other adverse events | 75 / 204 | 78 / 204 | 70 / 206 |
| serious Total, serious adverse events | 3 / 204 | 2 / 204 | 4 / 206 |
Outcome results
Primary
Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Syndrome Scale (PANSS) Total Score: Change From Baseline to Week 6.
To evaluate efficacy and safety of HP-3070 compared with placebo for the treatment of schizophrenia as evaluated by Positive and Negative Syndrome Scale (PANSS) total score. The PANSS total score is the sum of all 30 items (7 positive items, 7 negative items, and 16 general psychopathology items). For each item, severity was rated on an anchored 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. If one or more items are missing at a given assessment, the total score is set to missing. Total score ranges from 30 to 210. Score indicates severity of the disease, i.e. low score = low severity.
Time frame: 6 weeks
Population: Results are from the full analysis set (FAS) which includes all randomized participants who had at least 1 patch of double-blind study medication applied and who have a baseline PANSS total score and at least 1 post baseline assessment of the primary efficacy measure (PANSS total score) and completed the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Asenapine Maleate Patch | Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Syndrome Scale (PANSS) Total Score: Change From Baseline to Week 6. | -22.1 score on a scale | Standard Error 1.158 |
| High Dose Asenapine Maleate Patch | Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Syndrome Scale (PANSS) Total Score: Change From Baseline to Week 6. | -20.4 score on a scale | Standard Error 1.162 |
| Placebo Patch | Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Syndrome Scale (PANSS) Total Score: Change From Baseline to Week 6. | -15.5 score on a scale | Standard Error 1.166 |
Comparison: The mixed model for repeated measures includes treatment, country, visit, treatment by visit interaction, and baseline value as covariates, and participant as random effect. The correlation of repeated measures within a participant is estimated with an unstructured covariance matrix. The Kenward-Rogers method is used to estimate the denominator degrees of freedom.p-value: 0.00395% CI: [-8.06, -1.64]Mixed Model Repeated Measures Analysis
Comparison: The mixed model for repeated measures includes treatment, country, visit, treatment by visit interaction, and baseline value as covariates, and participant as random effect. The correlation of repeated measures within a participant is estimated with an unstructured covariance matrix. The Kenward-Rogers method is used to estimate the denominator degrees of freedom.p-value: <0.00195% CI: [-9.81, -3.4]Mixed Model Repeated Measures Analysis
Secondary
Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Clinical Global Impression - Severity of Illness Scale: Change From Baseline to Week 6.
To evaluate efficacy and safety of HP-3070 compared with placebo for the treatment of schizophrenia as evaluated by the Clinical Global Impression - Severity of Illness Scale. The severity of illness for each participant was rated using the CGI-S. The rater or Investigator answered the following question: Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?. Response choices included: 0 = not assessed; 1 = normal, not at all ill, 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
Time frame: 6 weeks
Population: Results are from the full analysis set (FAS) which includes all randomized participants who had at least 1 patch of double-blind study medication applied and who have a baseline PANSS total score and at least 1 post baseline assessment of the primary efficacy measure (PANSS total score) and completed the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Asenapine Maleate Patch | Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Clinical Global Impression - Severity of Illness Scale: Change From Baseline to Week 6. | -1.3 score on a scale | Standard Deviation 0.9 |
| High Dose Asenapine Maleate Patch | Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Clinical Global Impression - Severity of Illness Scale: Change From Baseline to Week 6. | -1.2 score on a scale | Standard Deviation 0.96 |
| Placebo Patch | Evaluate Efficacy and Safety of Asenapine Maleate Patches Compared With Placebo Patches in Subjects Diagnosed With Schizophrenia as Measured Using the Clinical Global Impression - Severity of Illness Scale: Change From Baseline to Week 6. | -0.9 score on a scale | Standard Deviation 0.93 |
Comparison: The mixed model for repeated measures includes treatment, country, visit, treatment by visit interaction, and baseline value as covariates, and participant as random effect. The correlation of repeated measures within a participant is estimated with an unstructured covariance matrix. The Kenward-Rogers method is used to estimate the denominator degrees of freedom.p-value: <0.00195% CI: [-0.55, -0.16]Mixed Model Repeated Measures Analysis
Comparison: The mixed model for repeated measures includes treatment, country, visit, treatment by visit interaction, and baseline value as covariates, and participant as random effect. The correlation of repeated measures within a participant is estimated with an unstructured covariance matrix. The Kenward-Rogers method is used to estimate the denominator degrees of freedom.p-value: <0.00195% CI: [-0.64, -0.25]Mixed Model Repeated Measures Analysis