An Open-Label, Randomized, Two-Treatment, Two-Period, Two-Sequence, Multiple-Dose, Steady-State, Fully Replicate, Crossover Bioequivalence Study of Aripiprazole 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection and Abilify Maintena® 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection in Adult Patients with Schizophrenia under Fasting Condition.
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 72
- 试验地点
- 12
- 主要终点
- To demonstrate the bioequivalence
研究概览
简要总结
This is an Open-Label, Randomized, Two-Treatment, Two-Period, Two-Sequence, Multiple-Dose, Steady-State, Fully Replicate, Crossover Bioequivalence Study of Aripiprazole 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection and Abilify Maintena® 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection in Adult Patients with Schizophrenia under Fasting Condition.
The study includes a screening period, a tolerability test period, a treatment period and end of study visit. All patients will undergo stabilisation period.
Visit Schedules:
Screening period: Screening safety assessments will be performed within 21 days prior to the initiation of stabilisation period.
Stabilisation period: Eligible patient on a stable regimen of oral aripiprazole 10-20 mg who require chronic antipsychotic treatment and who will benefit from initiating treatment with monthly regimen of marketed aripiprazole 400 mg powder and solvent for prolonged-release suspension for injection based on the judgment of the treating physician or Investigator, will switch from their oral aripiprazole dose regimen to a monthly regimen of aripiprazole 400 mg powder and solvent for prolonged-release suspension for injection until 3 consecutive monthly doses have been administered.
Treatment Period: During the treatment period, each patient will be randomised in a ratio of 1:1 to either of two sequences (Test product (T) to Reference product (R), or Reference product (R) to Test product (T) and receive six consecutive doses of 400 mg Test product (T) or 400 mg Reference product (R) of Aripiprazole Prolonged Release Injectable Suspension 400 mg/vial (2.0 mL) at predefined injection site into the gluteal (buttock) muscle region by deep intramuscular route 28 days apart in a crossover design during two periods (Period I and Period II).
Dosing and Administration: Each patient will be randomly assigned to receive test or reference product of Aripiprazole powder and solvent for Prolonged-Release Suspension for Injection 400 mg/vial (2.0 mL), at predefined injection site in the gluteal (buttock) region by deep intramuscular route, 28 days apart for consecutive six dosing’s (i.e. on Day-1, Day-29, Day-57, Day-85, Day-113, Day-141 in Period I) as per randomization schedule. Patients will then be switched over to the other treatment arm for the next consecutive six doses (i.e. on Day-169, Day-197, Day-225, Day-253, Day-281 and Day-309 in Period II).
Housing Details:
During the stabilisation period all patients will need to remain in the study centre on the day of injection for at least 2 hours before dosing and at least 2 hours after dosing.
During the treatment period, all patients will be housed in the study centre as mentioned below:
| Period |
Dose
Check-In
Check-Out
|I
1 to 4
2 hours before
dosing
4 hours after
dosing
|II
5 and 6
10 hours before
dosing
24 hours after
dosing
|I
7 to 10
2 hours before
dosing
4 hours after
dosing
|II
11 and 12
10 hours before
dosing
24 hours after
dosing
Collection of Blood samples:
All blood samples (3.0 mL each) will be collected in labelled K2EDTA-vacutainers.
A total of 86 blood samples per each patient will be collected including the pre-dose blood samples, throughout the whole study duration.
Food and Fluid Restrictions: Food and fluid instruction needs to be followed as per protocol.
Assessments: As this drug may cause suicidal behaviour and extrapyramidal side effects, evaluation of suicidal behaviour (using C-SSRS scale), neuroleptic malignant syndrome and any extra pyramidal adverse event assessment will be performed at regular interval during the study.
Additionally, CGI evaluation will also be performed to evaluate changes in the disease condition during the study. Other standard safety assessments like vital signs, physical examination, AE assessment, and laboratory tests will be performed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or non-pregnant, non-lactating female patient between 18 and 65 years of age (both inclusive).
- •Patient with documented diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders – 5th edition (DSM-V) criteria.
- •Patient with Body Mass Index (BMI) ≥18 to less than 30 kg/m2 and weight not less than 50 kg.
- •Patient who is clinically stable and have had no hospitalization for exacerbation of psychiatric symptoms during the 3 months before screening and till randomization.
- •Patient is clinically stable on aripiprazole 10-20 mg for the past 3 months who require chronic antipsychotic treatment and who will benefit from initiating treatment with aripiprazole 400 mg powder and solvent for prolonged-release suspension for injection.
排除标准
- •Patient with known or suspected allergy or hypersensitivity to aripiprazole or other constituents of the formulation.
- •Patient having signs and symptoms suggestive of COVID-19 (such as fever, dry cough, difficulty in breathing, fatigue etc.)
- •History of medically significant adverse events or intolerance with aripiprazole based on investigators discretion.
- •Patient on drugs known to be inducer or inhibitor of CYP3A4 and CYP2D6 enzymes (allowed if on a stable regimen of at least 1 month based on Principal Investigators discretion) Note: a.
- •If the patient was on any of these drugs, sufficient wash out period (of at least 5 half-lives) must have elapsed since the last dose of such drug and the first dose of study medication.
- •Individuals with co-administered weak CYP3A4 and CYP2D6 inhibitors will be allowed if on a stable regimen of at least 1 month based on Principal Investigator’s discretion in consultation with medical monitor and with plans to remain on that stable regimen throughout the course of this study.
- •Patient who is poor metabolizer of CYP2D6 enzyme.
- •Patient with Clinical Global Impression – Severity of illness (CGIS) score of 5 or more.
- •Patient with inadequate muscle mass to receive the intramuscular injection according to the investigator.
- •Patient with a history of Neuroleptic Malignant Syndrome (NMS) or tardive dyskinesia while on treatment with atypical antipsychotics.
- •Patient with dementia related psychosis.
- •History or presence of pathological gambling and other compulsive behaviors.
- •Patient with history or presence of seizures or other conditions that potentially lower the seizure threshold.
- •Presence of significant orthostatic hypotension (i.e., decrease in systolic blood pressure ≥20 mmHg or diastolic BP of ≥10 mmHg when comparing standing to supine values) or uncontrolled hypertension (systolic BP ≥150 mmHg/diastolic BP ≥ 100 mmHg).
- •Patient with known cardiovascular disease (example, heart failure, history of myocardial infarction or ischemia), cerebrovascular disease, or conditions that predispose the patient to hypotension (example, dehydration, hypovolemia, and treatment with antihypertensive medications), uncontrolled metabolic disorders including uncontrolled hyperglycemia/diabetes mellitus (HbA1c ≥ 9 %) or Dyslipidemia.
- •Patient with a history of a corrected QT interval greater than 450 msec (Bazett’s formula)
- •History of drug induced leukopenia/neutropenia/agranulocytosis.
- •Total white blood cell count less than 4000/mm
- •ANC less than 1500/mm
- •Platelet count less than 100,000/mm
- •Haemoglobin less than 9.0 gm/dl.
- •Patient with abnormal liver function tests at screening and randomization as defined by: a.
- •Bilirubin greater than 1.5 x ULN.
- •AST and ALT greater than 5 x ULN.
- •History of alcohol or substance abuse in the immediate 6-month period prior to screening.
- •Patient who smokes or chews tobacco products.
- •Any changes in antipsychotic medication or dosage during the past 3 months prior to the randomization.
- •Received Electroconvulsive Therapy (ECT) within the last 3 months prior to screening.
- •Patient with suicidal ideation (score of 4 or 5 on the Columbia Suicide Severity Rating Scale [C-SSRS]) within the past 2 months or any suicidal behavior occurring in the past year.
- •Patient who had major surgery within 4 weeks prior to study entry, who have not recovered from prior major surgery, or who have surgery scheduled during the course of the study.
- •Patient with known positivity for human immunodeficiency virus (HIV), HBsAg and/or HCV, Syphilis (RPR/VDRL).
- •Patient with history or at risk of venous thromboembolism as per investigator’s discretion.
- •Patient having any other clinically significant finding of the physical examination or laboratory value or any reason which, in the opinion of the investigator, would prevent the patient from safely participating in the study.
- •Male or female of childbearing potential unwilling to use adequate methods of contraception throughout the study.
- •History of difficulty with donating blood or difficulty in accessibility of veins.
- •Donation of blood (1 unit or 350 mL) within 90 days prior to receiving the first dose of investigational medicinal product in the study.
- •Institutionalized patient.
结局指标
主要结局
To demonstrate the bioequivalence
时间窗: End of Study: Week 49 (Day 337)
次要结局
- To evaluate the safety and tolerability(End of Study: Week 49 (Day 337))
研究者
Dr Dharmesh Domadia
Cliantha Research Limited