Schizophrenia
Conditions
Brief summary
This study is to evaluate the pharmacokinetics (PK), safety and tolerability of Brexpiprazole, administered subcutaneously, in subjects with schizophrenia.
Interventions
DRUGBrexpiprazole for ER injection, 45 mg
Single-dose, Subcutaneous
DRUGBrexpiprazole for ER injection, 100 mg
Single-dose, Subcutaneous
Sponsors
Bostal Drug Delivery Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects and/or subject's legally acceptable representative (LAR) is able to sign informed consent and subject is willing to comply with the trial protocol and to attend the clinic visits. 2. Male or female subjects diagnosed with schizophrenia as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) (or later) criteria. 3. Subjects with a Clinical Global Impression-Severity of Illness (CGI-S) Score of ≤ 4 at screening and on enrolment prior to IP dosing (Day -1). 4. Subjects with Positive and Negative syndrome-scale (PANSS) total score ≤75 at screening and on enrolment prior to IP dosing (Day -1). 5. Subjects aged 18-65 years (both inclusive) having Body Mass Index (BMI) between 18.50 to 30.00 kg/m2 6. Schizophrenic subjects who are clinically stable on their current antipsychotic medication other than Brexpiprazole, for a duration of at least 8 weeks prior to screening. \[Refer to Appendix A for List of Allowable medications\] NOTE: Subjects must NOT be taking \> 2 antipsychotic medications for their disease 7. Subjects who have tolerated oral Brexpiprazole prior to dosing. 8. Subjects with acceptable haematology status: * Hemoglobin ≥ 9 g/dL * Absolute neutrophil count (ANC) ≥ 1500 cells/μL * Platelet count ≥ 100,000 cells/μL * White blood cell count (WBC) ≥ 4000 cells/μL 9. Subjects with acceptable liver function: * Alanine aminotransferase (ALT) ≤ 2 X upper limit of normal (ULN) * Aspartate aminotransferase (AST) ≤ 2 X ULN * Bilirubin \< 1.5 X ULN * Alkaline phosphatase ≤ 2 X ULN 10. Subjects with creatinine clearance ≥ 60 mL/minute (using the Cockcroft- Gault Equation). 11. Female subjects of childbearing potential with negative pregnancy test at screening and at enrolment day, and agree to practice acceptable methods of contraception during the study. Acceptable methods of contraception are: * Oral or other (e.g. injection, patch or implant) hormonal contraception which has been used continuously for at least one month prior to the first dose of study medication * Intrauterine device (IUD) or intrauterine system (IUS) * Double barrier method of contraception (condom and occlusive cap or condom and spermicidal agent) * Female sterilization (surgical bilateral oophorectomy) or tubal ligation at least 6 weeks prior to study participation 12. Subjects who agree to avoid drinking alcohol during the study. 13. Subjects with accessible vein access from arm.
Exclusion criteria
1. Subjects with known hypersensitivity to Brexpiprazole or related class of drugs or to any of the excipients of the formulation. 2. Subjects currently in acute, manic episodes of schizophrenia, as assessed by the Investigator. 3. Subjects with history of or a current DSM-5-TR diagnosis of concurrent mental disorder besides schizophrenia (e.g., schizoaffective-disorder, major depressive disorder, bipolar I disorder, bipolar II disorder, general anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, dementia or mild neurocognitive disorder, and personality disorder). 4. Subjects who have any suicidal ideation based on history, routine psychiatric status examination, investigator's judgment, or who have an answer of "yes" on any of the questions of 'Suicidal Ideation' on the CSSRS for screening. \[Refer to Appendix B\] 5. Subjects with history or presence of neuroleptic malignant syndrome (NMS), tardive dyskinesia, Parkinson's disease, epilepsy or other seizure disorders, cognitive and motor impairment, pathological gambling, dysphagia or other compulsive behaviour 6. Subjects with a prior personal or family history of dystonic reactions to medications. 7. Subjects with clinically significant dyslipidemia. 8. Subjects with a history of syncope or a presence of significant orthostatic hypotension (i.e., a drop in systolic blood pressure of 20 mm Hg or more and/or a drop in diastolic blood pressure of 10 mm Hg or more within 3 minutes of standing from a minimum of 5 minutes in supine position) at screening. 9. Subjects with known history or presence of any systemic disease (e.g., cardiovascular disease, cerebrovascular disease, diabetes mellitus, etc.) 10. Subject who are on concurrent treatment with other anti-psychotic Longacting Injection (LAIs). 11. Subject who has received concomitant medications that are strong CYP3A4 inhibitors, CYP2D6 inhibitors, or CYP3A4 inducers within 14 days prior to study drug administration (or within five half-lives since the last drug administration, whichever is greater), or is expected to require such treatment during the study. 12. Subjects with any other medical condition or serious inter-current illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study including but not limited to cirrhosis or psychiatric illness other than schizophrenia /social situations that would limit adherence to study requirements. 13. Any other condition(s) which could significantly interfere with protocol compliance 14. Subjects found positive for urine screen for drugs of abuse (except for benzodiazepine, which is a permissible medication if supported by prescription) 15. Subjects with major surgical procedure (including periodontal) within 28 days of IP dosing or plan to have major surgical procedure during the study 16. Subjects with current surgical or other non-healing wounds. 17. Subjects who have participated in any clinical trial with another investigational drug or other investigational intervention within 90 days of enrolment. 18. Loss of ≥ 350 mL (1 unit) of blood within 90 days before enrolment in the study. 19. Subjects with history of difficulty with donating blood or difficulty in accessibility of veins. 20. Subjects with positive serology for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV). Note: Subjects with Hepatitis B core antibody (HBcAb) positive result can be enrolled if a confirmatory negative test is obtained suggestive of no active infection currently. 21. Alcoholics (alcohol consumption of more than 14 units per week for men and more than 7 units per week for women, each unit equivalent to 360 mL of beer or 150 mL of wine or 45 mL of spirits with 40% alcohol content) or those who have a positive urine alcohol test 22. Subjects who have consumed tobacco-containing products (smoking, tobacco chewing, etc.), xanthine containing food, poppy seeds, and beverages (chocolates, tea, coffee, or cola drinks) or alcohol within 48.00 hours (02 days) prior to receiving the first dose of oral Brexpiprazole tablets for the tolerability assessment period (on Day -44) and within 48.00 hours (02 days) prior to IP dosing (on Day 1) or subject who is not ready to abstain from them till the last PK sample collection for oral Brexpiprazole tablets (on Day -27) and till 30 days after the IP administration on Day 1. 23. Subjects who have consumed grapefruit or its juice and cranberry juice within 96.00 hours (04 days) prior to dosing or subject who is not ready to abstain from them till last study-related procedure. 24. Subjects currently smoking greater than or equal to 10 cigarettes or equivalent per day. 25. Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Pre-dose to 190 days post-dose | Maximum peak plasma concentration |
| Clast | Pre-dose to 190 days post-dose | Last measurable plasma concentration |
| Tmax | Pre-dose to 190 days post-dose | Time of occurence of Cmax |
| AUC0-last | Pre-dose to 190 days post-dose | Area under curve from time zero to last measurable concentration |
| Kel | Pre-dose to 190 days post-dose | — |
| T1/2 | Pre-dose to 190 days post-dose | Half-life |
| Vd/F | Pre-dose to 190 days post-dose | Volume of distribution |
| CL/F | Pre-dose to 190 days post-dose | Apparent clearance of drug from plasma |
| MRT | Pre-dose to 190 days post-dose | Mean residence time of the drug in the body |
| AUC_%Extrap_obs | Pre-dose to 190 days post-dose | Percentage of AUC due to extrapolation from Tlast to infinity |
| AEs | Day 1 to Day 190 | Adverse events |
| SAEs | Day 1 to Day 190 | Serious AEs |
| Change from baseline in physical examination findings | Day 1 to Day 190 | Change from baseline in clinical physical examination findings will be assessed descriptively for safety monitoring. The assessment includes general appearance, skin, head, ears, eyes, nose and throat, chest and lungs, cardiovascular, abdomen, musculoskeletal and extremities, neurological, psychiatric, and mental status examinations. Individual findings will be evaluated for clinically meaningful changes from baseline. |
| Blood Pressure | Day 1 to Day 190 | Evaluate the clinical significance of test value outside of the reference range. |
| Orthostatic hypotension | Day 1 to Day 190 | Drop in blood pressure due to a change in body position from standing to supine |
| Columbia-Suicide Severity Rating Scale (C-SSRS) assessment | Day 1 to Day 190 | Change in suicidality from baseline. |
| Clinical Laboratory Tests | Day 1 to Day 190 | Evaluate the clinical significance of each test value outside of the reference range. Lab tests including blood test for Human immunodeficiency virus (HIV), Hepatitis B virus (HBsAg and HBcAb) and Hepatitis C virus (HCV), haematology (Total WBC count, total RBC count, hemoglobin, HCT (PCV), lymphocytes, monocytes, granulocytes, platelet count, and ANC), biochemistry (Fasting blood glucose, BUN, serum creatinine, creatinine clearance, total bilirubin, SGPT, SGOT, ALP, serum cholesterol, sodium, calcium, potassium, chloride, magnesium, LDL, HDL and TG), serum pregnancy test (only for females of childbearing potential) and urine test |
| 12-lead ECG Assessment | Day 1 to Day 190 | For safety assessment. ECG findings will be evaluated descriptively based on the overall interpretation (Normal, Abnormal Not Clinically Significant \[NCS\], or Abnormal Clinically Significant \[CS\]). |
| Pulse Rate | Day 1 to Day 190 | Evaluate the clinical significance of test value outside of the reference range. |
| Respiratory Rate | Day 1 to Day 190 | Evaluate the clinical significance of test value outside of the reference range. |
| Body Temperature | Day 1 to Day 190 | Evaluate the clinical significance of test value outside of the reference range. |
Outcome results
None listed