Health Condition 1: F20- Schizophrenia
Conditions
Interventions
Intervention1: AX251 Long-Acting Injectable (AX251 LAI): Dose: Cohort 1 45 mg, Cohort 2- 90 mg, Cohort 3 135 mg, Cohort 4 180 mg
Dosage: Injection
Route of Administration: Intramuscular (gluteal
Sponsors
Anxo Pharmaceutical Co., Ltd.
CBCC Global Research
Eligibility
Inclusion criteria
Inclusion criteria: Subjects will be considered eligible for the study based on the following criteria: 1. Male or female subject aged between 18 and 65 years, both inclusive. 2. Subject has a clinical diagnosis of schizophrenia as per DSM 5 TR or later criteria at screening. 3. Subject has a body mass index, in kilograms per meter squared, between 18 point 5 and 35 point 0, inclusive, at screening. 4. Subject has a Clinical Global Impression Severity score of less than or equal to 4 at screening. 5. Subject has a Positive and Negative Syndrome Scale total score of less than or equal to 75 at screening. 6. Subject is clinically stable on their current antipsychotic medication, other than cariprazine, for at least 3 months prior to screening. Subject must not be taking more than 2 antipsychotic medications for their disease. 7. Subject is able to remain at the study site for 7 days following AX251 long acting injectable administration. 8. Subject is physically and mentally fit to participate in the study, as determined by the investigator using standard clinical evaluation, including physical examination, 12 lead electrocardiogram, and laboratory assessments. 9. Subject has acceptable hematology status: a. Hemoglobin greater than or equal to 9 grams per deciliter b. Absolute neutrophil count greater than or equal to 1500 cells per microliter c. Platelet count greater than or equal to 100000 cells per microliter d. White blood cell count greater than or equal to 4000 cells per microliter 10. Subject understands and agrees to adhere to study procedures and requirements. 11. Subject agrees to use protocol defined birth control during the study period. 12. Subject has prior experience tolerating oral cariprazine at doses of 1 point 5, 3, 4 point 5, or 6 milligrams, corresponding to AX251 long acting injectable doses of 45, 90, 135, and 180 milligrams, respectively.(subject does not have such experience, the investigator will initiate oral cariprazine starting at 1 point 5 milligrams and titrate to the appropriate dose level based on clinical response and tolerability for 2 to 7 days, days followed by mandatory washout to become eligible).
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study based on the following criteria: 1. Subject has a clinical diagnosis of a concurrent mental disorder other than schizophrenia, such as schizoaffective disorder, major depressive disorder, bipolar one disorder, bipolar two disorder, generalized anxiety disorder, obsessive compulsive disorder, post traumatic stress disorder, dementia or mild neurocognitive disorder, and personality disorder, as defined by DSM 5 TR criteria. This exclusion does not apply to caffeine related or tobacco related disorders. 2. Subject meets DSM 5 TR criteria for a substance related or addictive disorder, including alcohol and benzodiazepines, but excluding caffeine and tobacco, within 180 days prior to screening. 3. Subject has a history of neuroleptic malignant syndrome, seizure disorder, or clinically significant tardive dyskinesia, akathisia, or extrapyramidal symptoms. 4. Subject has current or past clinically significant manifestations of cardiovascular, hematologic, metabolic, hepatic, renal, immunological, or neurological conditions which, in the opinion of the investigator, would significantly limit the subject s ability to complete or participate in this study. 5. At screening, the subject exhibits severe hepatic impairment, classified as Class C based on the Child Pugh Score. The scoring criteria are as follows: Albumin: Greater than 3 point 5 milligrams per milliliter equals a score of 1. Between 2 point 8 and 3 point 5 milligrams per milliliter equals a score of 2. Less than 2 point 8 milligrams per milliliter equals a score of 3. Bilirubin: Less than 2 milligrams per milliliter equals a score of 1. Between 2 and 3 milligrams per milliliter equals a score of 2. Greater than 3 milligrams per milliliter equals a score of 3. Ascites: None equals a score of 1. Mild equals a score of 2. Moderate equals a score of 3. Encephalopathy: None equals a score of 1. Grade 1 or Grade 2 equals a score of 2. Grade 3 or Grade 4 equals a score of 3. Prothrombin time prolongation: Less than 4 seconds equals a score of 1. Between 4 and 6 seconds equals a score of 2. Greater than 6 seconds equals a score of 3. Prothrombin time International Normalized Ratio: Less than 1 point 7 equals a score of 1. Between 1 point 7 and 2 point 2 equals a score of 2. Greater than 2 point 2 equals a score of 3. Total score interpretation: A total score of 5 to 6 corresponds to Class A. A total score of 7 to 9 corresponds to Class B. A total score of 10 to 15 corresponds to Class C. 6. Subject has a known history or presence of uncontrolled hypertension. 7. Subject has clinically significant electrocardiogram abnormalities, as determined by the investigator. 8. Subject has severe renal impairment, defined as an estimated glomerular filtration rate less than 30 milliliters per minute. 9. Subject has a history of syncope or the presence of significant orthostatic hypotension, defined as a decrease in systolic blood pressure of 20 millimeters of mercury or more or a decrease in diastolic blood pressure of 10 millimeters of mercury or more within 3 minutes of standing from a supine position, at screening. 10. Subject fails to meet the mandatory washout period, defined as at least 5 half lives, for prohibited concomitant medications prior to initiation of AX251 long acting injectable administration. 11. Subject is receivi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the PK, safety, and tolerability of AX251 LAI administered as a single dose in patients with schizophreniaTimepoint: Day 1 (pre-dose & 1, 2, 3, 4, 8, 12, 24 hours post-dose) and Days 3, 5, 7, 14, 21, 28, 42, 56, and 70) | — |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAEs) during the study period Change from baseline in safety parameters during the study period including vital signs, orthostatic hypotension, physical examinations, electrocardiogram (ECG), hematology, and laboratory findings, PANSS total score, CGI-S, CGI-I score, C-SSRS score, AIMS score, BARS score, SAS score Subject injection site pain assessment on a Likert scale of 0 to 10 (0 = no pain, 10 = worst pain imaginable) during the study period Timepoint: Screening (Day -137 to -110) / Screening-2 (Day -28 to -1) to EOS (Day 70) | — |
Countries
India
Contacts
Public ContactDr Sandeep Singh
CBCC Global Research
Outcome results
None listed