Schizophrenia MedDRA version: 8.1 Level: LLT Classification code 10039626 Term: Schizophrenia
Conditions
Interventions
Product Code: AZD3480
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ispronicline
CAS Number: 691882-47-0
Current Sponsor code: TC-1734-226
Concentration unit: mg milligram(s)
Concentration t
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study patients must fulfil all of the following criteria: 1. Patients able to communicate with the study personnel, able to understand and are willing to comply with study procedures, restrictions and requirements. 2. Provision of signed Informed Consent, including genetic sampling for CYP2D6. 3. Genotyped to be rapid metabolisers or slow metabolisers with regard to CYP2D6. Rapid metabolisers, in this study, is defined as individuals with at least one fully functional CYP2D6 allele (CYP2D6*1, CYP2D6*2, CYP2D6*35) on one of the two chromosomes and slow metabolisers as the rest of the genotypes. (Patients receiving potent CYP2D6 inhibitors such as paroxetine and fluoxetine will functionally be characterised as belonging to the slow metaboliser group). 4. Male and female schizophrenic patients, aged 20 to 65 years (inclusive), clinically stable and in the residual (non-acute) phase of their illness for at least 3 months. 5. Receiving treatment with oral quetiapine, risperidone or olanzapine for at least 2 months, at the current dose schedule for at least the last month. 6. At screening, showing not more than “moderate” severity of hallucinations and delusions (PANSS item P3: Hallucinatory Behaviour = 4 , and PANSS item G9: Unusual Thought Content item score = 4), positive formal thought disorder (PANSS item P2: Conceptual Disorganization item score = 4), or negative symptoms (PANSS negative syndrome total score = 22, scale range 1-7). Minimal level of EPS (SAS total score = 6) and depressive symptoms (CDS for Schizophrenia total score = 10). 7. Clinically normal physical findings, including BP, heart rate, baseline ECG and laboratory assessments as judged by the investigator. 8. Documented clinical diagnosis meeting DSM-IV criteria for any of the following: Schizophrenia DSM-IV catatonic 295.20 disorganised 295.10 paranoid 295.30 undifferentiated 295.90 residual 295.60 9. BMI (body weight/height2) 19 to 30 kg/m2. For inclusion in the additional genetic component of the study, patients must fulfil the following criterion: 1. Provision of informed consent for additional genetic research. If a patient declines to participate in the additional genetic component of the study, there will be no penalty or loss of benefit to the patient and the patient will not be excluded from other aspects of the study described in the Clinical Pharmacology Study Protocol, as long as they have given consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Any of the following is regarded as a criterion for exclusion from the study: 1. Clinically significant illness, apart from schizophrenia, within the two weeks prior to the first dose of the investigational product, including a suspected/manifested infection according to World Health Organisation (WHO) risk categories 2, 3 or 4, as judged by the investigator. 2. Diagnosis of any DSM-IV Axis I disorder other than those included in inclusion criteria (3) above (eg, alcohol dependence or psychoactive substance dependence not in full remission, concurrent organic mental disorder, schizophreniform and schizoaffective disorder) or mental retardation, of a degree that may interfere with the patient’s ability to co-operate. 3. History of clinically significant cardio-or cerebrovascular, pulmonary, renal, hepatic, neurological, mental (apart from schizophrenia), heamatologic or gastrointestinal disorder or any other major disorder that may interfere with the objectives of the study, as judged by the investigator. 4. ECG result considered showing clinically significant abnormality as determined by an experienced cardiologist. 5. QT interval corrected for heart-rate, where the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QTc) Bazett >450 ms taken from the ECG at baseline as determined by an experienced cardiologist. 6. A patient with diabetes mellitus (DM) fulfilling one of the following criteria (Note: If a diabetic patient meets one of these criteria the patient will be excluded even if the treating physician believes that the patient is stable and can participate in the study): -unstable DM defined as enrolment glycated haemoglobin A1c (HbA1c) >8.5% - admitted to hospital for treatment of DM or DM related illness in the past 12 weeks - not under care of physician responsible for patient’s DM care - physician responsible for patient’s DM care has not indicated that the patient’s DM is controlled - physician responsible for patient’s DM care has not approved patient’s participation in the study - has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the last 4 weeks prior to enrolment. For thiazolidinediones (glitazones) this period should not be less than 8 weeks - taking insulin where the daily dose on one occasion has been more than 10% above or below the patient’s mean dose in the 4 weeks preceding enrolment. 7. Known or suspected drug or alcohol abuse or positive drugs of abuse test as judged by the investigator. 8. Patient who has received any investigational drug and/or has participated in a clinical study during the last 3 months before first administration of investigational drug. 9. Donation of blood within 3 months prior to enrolment. 10. Donation of plasma within 14 days prior to enrolment. 11. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity (except for seasonal hay fever) as judged by the investigator. 12. Excessive use of caffeine containing drinks (equivalent to more than 5 cups of coffee per day). 13. Pregnancy or lactation. Female patients must not be at risk of pregnancy and must use a reliable method of birth control, ie, double barrier method, oral contraceptive, implant, long-term injectable contraceptive, intrauterine device, or tubal ligation. 14. Patients injected with depot antipsychotic drugs during the last 3 months, including depot, risperidone and olanzapine. 15. Previous bone marrow
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and tolerability of multiple ascending oral doses of AZD3480 when administered to schizophrenic patients on stable antipsychotic monotherapy with either quetiapine, risperidone or olanzapine. ;Secondary Objective: 1. To investigate the pharmacokinetic (PK) interaction between AZD3480 and three commonly used antipsychotic drugs. 2. To investigate the dose-concentration-effect relationship by exploring the AZD3480 effect on cognition in schizophrenic patients on stable antipsychotic monotherapy. 3. To explore the effect of AZD3480 on severity of schizophrenic illness. 4. To explore the effect of AZD3480 on antipsychotic drug-related extra pyramidal symptoms (EPS). ;Primary end point(s): Primary endpoints: Safety & tolerability: laboratory assessments, vital signs, physical examination, concomitant medication and adverse events (AEs) | — |
Countries
Hungary, Latvia
Outcome results
None listed