| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10039626 |
| E.1.2 | Term | Schizophrenia |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to evaluate efficacy of HP-3070 compared with placebo for the treatment of schizophrenia as evaluated by PANSS total score. |
|
| E.2.2 | Secondary objectives of the trial |
Key Secondary Efficacy Objective:
-Clinical Global Impression Severity of Illness Scale
Other Secondary Efficacy Objectives: To evaluate the efficacy of HP-3070 using the following measures:
-PANSS total score at each time point
-Clinical Global Impression Severity of Illness Scale at each time point
-Clinical Global Impression Improvement Scale at each time point
-Proportion of CGI-I responders at each time point including Week6; CGI-I responders are defined as subjects who have a score of 1 or a score of 2
-Positive, negative, and general pathology subscores of PANSS
-Proportion of PANSS responders
-Calgary Depression Scale for Schizophrenia
-Medication Satisfaction Questionnaire score
Safety Objectives:
-Adverse events, including TEAEs, AEs leading to discontinuation from the study drug, serious adverse events, and deaths
-Change from Baseline in cl. laboratory results, ECG results, body weight, and vital signs
-Results of C-SSRS, BARS, AIMS, SAS
- dermal safety |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Adult male or female subjects, ≥18 years of age.
2. Subject is able to undergo informed consent process and signs ICF.
3. Subject has current diagnosis of schizophrenia as per DSM-5 Criteria, Mini
International Neuropsychiatric Interview (MINI), and as confirmed by Investigator
assessment.
4. 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:
a. Conceptual disorganization
b. Delusions
c. Hallucinatory behavior
d. Unusual thought content
5. Subject has CGI-S scale score of ≥4 (moderately ill) at Screening and Baseline.
6.Subject has history of relapse and/or exacerbation of symptoms when they are not receiving antipsychotic treatment, excluding the current episode.
7. Subject is confirmed by the Investigator to be experiencing an acute exacerbation of schizophrenia, as evidenced by ALL of the following:
a. The duration of the current episode is no more than 8 weeks.
b. The subject’s current symptoms represent a marked and substantial
exacerbation of schizophrenia compared with the subject’s symptomatic state
prior to the emergence of the current episode.
c. A corresponding functional deterioration to the symptomatic exacerbation is
evident.
8. Subject has not been hospitalized for more than 21 days for the current episode by the day of the Screening Visit, not including social hospitalization (e.g., homelessness or need for shelter that is unrelated to the subject’s underlying psychiatric condition).
9. Subject agrees not to begin formal, structured psychotherapy targeting the symptoms of schizophrenia from the time of the Screening Visit until the last dose of study drug.
10. Subject would benefit from hospitalization or continued hospitalization for the treatment of schizophrenia (as determined by the Investigator).
11. Subjects must not be treatment naïve or treatment resistant. Treatment resistance is defined as having little or no symptomatic response to at least 2 courses of antipsychotic treatment of an adequate duration (at least 6 weeks) and at a therapeutic dose (according to the drug’s package insert).
12. Subject has had previous positive response to an antipsychotic medication other than clozapine in a prior episode.
13. Subject has a stable living situation and caretaker support when not hospitalized.
14. Subject is male, or a female who is not of childbearing potential (i.e., surgically sterile, postmenopausal for at least 1 year) or who is non-pregnant, non-lactating, and is using a medically accepted method of contraception.
15. Subjects must agree that they will not donate sperm or eggs from the time of the Screening Visit until 3 months following administration of the last treatment or dose of study medication.
16. Agrees not to use any other transdermal patch products (e.g., nicotine replacement patch, hormonal replacement patch, etc.) for the duration of the study.
17. Subject must be able to wear a transdermal patch for 24 hours. |
|
| E.4 | Principal exclusion criteria |
1.Subject is presenting with a first episode of schizophrenia based on the clinical
judgment of the Investigator.
2. Subject has been diagnosed with schizophrenia less than 6 months prior to Screening Visit.
3. Subject has received electroconvulsive therapy (ECT), transcranial magnetic
stimulation (TMS), vagal nerve stimulation (VNS), or other brain stimulation
treatments within 90 days of Screening Visit.
4. Subject has a current DSM-5 diagnosis other than schizophrenia including (but not limited to) schizoaffective disorder, major depressive disorder, bipolar disorder, posttraumatic stress disorder, anxiety disorders, delirium, dementia, amnestic, or other cognitive disorders.
5. Subject has a diagnosis of mental retardation, history of traumatic brain injury
causing ongoing cognitive difficulties, Alzheimer’s Disease or another form of
dementia (or suspicion thereof), or any chronic organic disease of the central nervous system that would interfere with the efficacy or safety endpoints of the study.
6. Subject has experienced acute depressive symptoms within 30 days prior to Screening Visit that requires treatment with an antidepressant, as determined by the Investigator.
7. Subject is a known non-responder to previous asenapine treatment, as per Investigator judgment.
8.Subject is currently taking clozapine for the treatment of schizophrenia. Subjects taking low doses of clozapine (up to 100 mg/day) for sedative properties and not treatment resistance or suicidality may be acceptable as per Investigator judgment and as approved by the Sponsor/designee.
9. Subject with schizophrenia who is considered resistant/refractory to antipsychotic treatment by history or who has a history of failure to respond to clozapine or response to clozapine treatment only. Treatment resistance is defined as having little or no symptomatic response to at least 2 courses of antipsychotic treatment of an adequate duration (at least 6 weeks) and at a therapeutic dose.
10. Subject who is unwilling to discontinue or, in the opinion of the Investigator, unable to discontinue any prohibited medication prior to the Baseline Visit without significant medical or psychiatric destabilization, or increased suicidality, as per the washout requirements.
11. Subjects taking drugs (current antipsychotic or other prohibited medication) that require >14 days for washout
12. Subject who is involuntarily committed, incarcerated, or under legal compulsion to seek psychiatric treatment.
13. Subject currently has clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders such as any history of myocardial infarction, congestive heart failure,human immunodeficiency virus (HIV) seropositive status/acquired immunodeficiency syndrome (AIDS).
14. Subject has any other medical condition or laboratory result that, in the opinion of the Investigator make the subject unsuitable.
Subjects with the following laboratory test and ECG results are excluded:
a. Platelets ≤75,000/mm3
b. Hemoglobin ≤9 g/dL
c. Neutrophils, absolute ≤1000/mm3
d. Aspartate transaminase (AST) >2×upper limit of normal (ULN)
i. QT interval corrected using Fridericia’s formula (QTcF) ≥450 msec (males),
QTcF ≥470 msec (females)
j. Prolactin
16. Subject with hypothyroidism or hyperthyroidism (unless condition has been stabilized with medications for at least the past 90 days); subjects with abnormal free T4 and thyroid stimulating hormone (TSH) levels.
17.Subject is currently treated with insulin for diabetes Subject has epilepsy or history of seizures, with the exception of a single seizure episode (e.g., childhood febrile, post traumatic).
19. Subject has uncontrolled hypertension (diastolic blood pressure [DBP] >95 mmHg in any position) or symptomatic hypotension, or orthostatic hypotension which is defined as a decrease of ≥30 mmHg in systolic blood pressure (SBP) and/or a decrease of ≥20 mmHg in DBP after at least 3 minutes standing compared with the previous supine blood pressure, OR development of symptoms.
20. Subject has a history of neuroleptic malignant syndrome.
21. Subject has a score of >2 (mild) on any item of the AIMS at Screening.
22. Subject has a score of 5 on BARS global clinical assessment of akathisia at Screening.
23. Subject has a history of pituitary adenoma or cancer <5 years prior to Screening.Subjects currently being treated for cancer may not be enrolled in the study.
24. Female subject to breastfeeding.
Female subject with a positive urine pregnancy test that is confirmed positive by
serum pregnancy test at Screening or Baseline.
26. Subject who currently (within the past 6 months) meets the DSM-5 criteria for substance use disorders |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is the change in PANSS total score between Baseline and Week 6. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
To evaluate the efficacy of HP-3070 compared with placebo for the treatment of
schizophrenia as evaluated by change in Clinical Global Impression – Severity of Illness-Scale (CGI-S) scores between Baseline and Week 6;
Other secondary efficacy endpoints include:
•Change from Baseline in PANSS total score at each time point in addition to Week 6
•Change from Baseline in CGI-S at each time point in addition to Week 6
•CGI-I score at each time point
•The proportion of CGI-I responders at each time point in addition toincluding Week 6; CGI-I responders are defined as subjects who have a score of 1 (very much improved) or a score of 2 (much improved)
•Change from Baseline in positive, negative, and general pathology subscores of PANSS at each time point
•Proportion of PANSS responders; PANSS responders are defined as subjects who have a ≥30% reduction in PANSS total score between Baseline and at each time point including Week 6
•Change from Baseline in CDSS score at each time point
•MSQ score at each time point
Safety Endpoints:
•AEs, including TEAEs, AEs leading to discontinuation from the study drug, SAEs, and deaths
•Change from Baseline in clinical laboratory results (including prolactin, fasting glucose, and lipids), ECG results, body weight and vital signs
•Results of C-SSRS, BARS, AIMS, and SAS
•Dermal safety
Exploratory Endpoints
•A model-based approach will be used to assess the impact of covariates on asenapine exposure and to explore the exposure-response relationship with relevant endpoints.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Bulgaria |
| Croatia |
| Romania |
| Russian Federation |
| Serbia |
| Slovakia |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| 30 days after last patch is removed |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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