A randomized, open label, multicenter, parallel group, multiple dose, steady state study to compare the bioavailability and characterize the pharmacokinetic profile of the sponsor’s test formulation [Paliperidone Palmitate extended release injectable suspension, (156 mg/ml)] relative to that of the reference formulation [Invega® Sustenna® (Paliperidone Palmitate extended release injectable suspension, 156 mg/ml), Janssen Pharmaceuticals, Inc., Titusville, New Jersey] and establish bioequivalence in patients of Schizophrenia already receiving a stable regimen of paliperidone palmitate extended release injectable suspension.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 240
- 试验地点
- 11
- 主要终点
- Comparision of the bioavailability and characterization of the pharmacokinetic profile of the Sponsor’s formulation with that of reference formulation and establish bioequivalence
研究概览
简要总结
It is an open label, multicenter, parallel group, multiple dose, steady state study. Paliperidone is a benzisoxazole derivative with potent antipsychotic properties, is indicated for the treatment of schizophrenia. The Sponsor has developed Paliperidone Palmitate extended release injectable suspension. This formulation being extended release formulation, it is expected to improve the compliance, which is very important considering schizophrenic population. This study is being conducted to characterize the pharmacokinetic profile and prove bioequivalence of the Sponsor’s formulation with respect to the reference formulation in Schizophrenic patients stabilized on Paliperidone Palmitate extended release injectable suspension, (156 mg/ml per month). As a high number of healthy subjects experienced serious adverse effects after administration of antipsychotics such as hypotension, tachycardia etc., hence, regulatory authorities are recommending that studies should be conducted on Schizophrenic patients. At the screening visit (within -2 weeks before the first dose visit), after giving informed consent, potential study participants will undergo screening examinations to assess eligibility for inclusion in the trial. The objective of the present study is to assess and compare the bioavailability and to characterize the pharmacokinetic profile of the Sponsor’s formulation (with respect to the reference formulation in schizophrenic patients and establish bioequivalence. Through this study, we will prospectively collect the data from adult schizophrenic patients who will be randomly assigned to receive either test product or reference product for the pharmacokinetic profiling.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Written informed consent for participation in the study by the patient and patient’s legal acceptable representative (LAR).
- •Schizophrenic male or female patients, between 18 and 75 years of age (both inclusive)
- •Patients having BMI between 18-35 kg per meter square (up to 2 percentage deviation is acceptable) and at least 50 kg weight for male patients and 48 kg for female patients.
- •Patients who are stabilized on 156 mg dose of paliperidone palmitate extended release injectable suspension once every month (atleast 3 doses prior to randomization) would be eligible to participate in the study by continuing their established maintenance dose.
- •Patients have a documented clinical diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition
- •Patients having Clinical Global Impression scale score of less than or equal to 4 at both screening and Baseline.
- •Patients not having any significant diseases or clinically significant abnormal findings except schizophrenia during screening, medical history, physical examination, 12-lead ECG recordings and Chest X-ray.
- •Adequate hematological parameters at screening and randomization
- •Adequate hepatic function at screening and randomization
- •Patients able to comply with study procedures in the opinion of the investigator.
- •In case of Male patients: Either partner or patient must use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
- •Cessation of birth control after this point should be discussed with a responsible physician.
- •Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug administration] sexual partner) for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug.
排除标准
- •Patients with current or relevant history of psychiatric illness except schizophrenia.
- •Patients with clinically significant illnesses or major surgery within 4 weeks prior to the screening.
- •Patients with DSM-V diagnosis of substance-related disorders within 180 days before the date of screening.
- •Patients with concurrent condition of Parkinson disease (except for drug-induced extrapyramidal syndrome).
- •Patients with history or presence of tardive dyskinesia.
- •Patients with cognitive and motor impairment.
- •Patients with concomitant treatment with hepatic enzyme inhibitors (including fluoxetine or paroxetine) or medications known to interact with study medication within 2 weeks of the first injection of study medication.
- •Administration of thioridazine, or ziprasidone within 2 weeks of the first study-related procedure; receiving tablet paliperidone within 2 months of the first study-related procedure.
- •Presence of syncope or orthostatic hypotension (defined as systolic blood pressure decrease of at least 30 mmHg or a diastolic blood pressure decrease of at least 20 mmHg within one to three minutes of standing up).
- •Patients with uncontrolled hypertension
- •Patients with known cerebrovascular disease, or conditions that predispose the patient to hypotension (e.g., dehydration, hypovolemia or any medications).
- •Patients with inadequate mass in the deltoid or gluteal regions to receive the intramuscular drug injection.
- •Patients with any condition which in the opinion of the investigator makes the patient unsuitable for inclusion.
- •Patients with creatinine clearance (using Cockcroft Equation) less than 80 mL per min
- •Patients with severe hepatic impairment based on the Child-Pugh classification
- •Patients with diagnosis of alcohol or substance dependence, with the exception of nicotine or caffeine dependence, within 12 months prior to screening, or diagnosis of substance abuse within 3 months prior to screening.
- •Donation of blood (greater than or equal to 1 unit or 350 mL) within 90 days prior to receiving the first dose of study medication or during the study.
- •Patient attempted suicide within 12 months before screening or current thoughts of suicide (suicidal ideation) or violent tendencies/ behavior.
- •Patients with positive result for any of the serology tests (Hepatitis B, C and HIV)
- •Patient with known hypersensitivity/ intolerance to study drug or any other component of the drug.
- •Positive tests for drug or alcohol abuse at screening and/or baseline.
- •Psychosis judged to be the direct physiological effect of an abused medication or substance.
- •Hospitalisation for an exacerbation of schizophrenia within two months prior to screening and during the screening period.
- •Patients with the following cardiac conditions are excluded: a.
- •Recent myocardial infarction (less than 12 months) b.QTc prolongation (screening electrocardiogram with QTc greater than 450 msec for men, QTc greater than 470 msec for women as calculated using Bazett’s Formula) c.
- •History of QTc prolongation or using concomitant medications which prolong QTc interval.
- •d.First-degree heart block with PR interval greater than 0.22 seconds.
- •Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia f.
- •Uncompensated congestive heart failure, myocarditis, cardiomyopathy g.Complete left bundle branch block.
- •Patients with uncontrolled Diabetes mellitus
- •A history of epilepsy or multiple syncopal episodes.
- •Patient with hyperprolactinemia at screening visit which as judged by Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial.
- •Dementia related psychosis.
- •Pregnant or lactating females.
结局指标
主要结局
Comparision of the bioavailability and characterization of the pharmacokinetic profile of the Sponsor’s formulation with that of reference formulation and establish bioequivalence
时间窗: Day 85, Day 113, Day 141, Day 142, Day 143, Day 144, Day 145, Day 146, Day 147, Day 148, Day 149, Day 150, Day 152, Day 154, Day 156, Day 158, Day 161, Day 165, Day 169
次要结局
- Safety of the patients who are exposed to the investigational medicinal product(Throughout the study)