A Randomised, Two-period, Two-sequence, Single-dose and Cross-over Study in Healthy Subjects to Demonstrate Pharmacokinetic Equivalence of Altebrel (Produced by Aryogen Pharmed) and Enbrel® (the Reference Drug, Produced by Amgen Company)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Area under the concentration-time curve from time zero to infinity (AUCinf)
研究概览
简要总结
This study aims to demonstrate pharmacokinetic (PK) similarity of biosimilar candidate Altebrel relative to etanercept reference product (Enbrel®) and evaluate safety and tolerability of Altebrel, in a crossover fashion in healthy male volunteers after administration of a single dose (25 mg) of etanercept.
The primary objective of this study is to demonstrate that the PK of Altebrel is similar to its originator, Enbrel®, as assessed by the area under the serum concentration time curve (AUC) from time 0 extrapolated to infinity (AUCinf) and the Cmax.
The secondary objectives of the study are:
To further compare the PK of Altebrel and Enbrel®. To assess the safety of Altebrel.
详细描述
This is a single-dose trial with one administration of each product (Altebrel and Enbrel®). Each subject participates in two treatment period, and are randomised to receive Altebrel or Enbrel® in a crossover fashion. The subjects are closely monitored during the following 24 hours (h), and are allowed to leave the site in the next morning post evaluation and blood samples are collected prior to and at the following time points after the dose: 6, 12 and 24 hours post-dose (on day 2). The subjects are requested to visit the trial site 36, 48, 60, 72, 96, 120, 144, 168, 216, 312 and 480 h after dose administration for blood sampling and evaluation of safety variable and tolerability.
Before initiation, the trial is reviewed by food and drug administration of Iran. The protocol, electronic case report form (eCRF), information for subjects and informed consent form are submitted to the ethics committees responsible for review and approval purposes, according to national regulatory guidelines.
In this study, no subject is recruited without an informed consent. All the informed consent forms which are signed by the subjects have two copies so that subjects could receive a copy of it.
This is a crossover trial with a single dose of Altebrel and Enbrel®, separated by 28 days. 34 (group A=17, group B=17) eligible subjects have been planned to enter to the study. All of whom are aged between 18 and 55 years. Subjects' randomization is done, using permuted block and subjects are assigned to treatment sequences AB or BA. Both groups receive 25 mg of either of the drugs as a single subcutaneous injection. The injection method and prefilled syringes are totally the same in both groups. The primary objective of this study is to demonstrate that the PK of Altebrel is similar to its originator, Enbrel®, as assessed by the area under the serum concentration time curve (AUC) from time 0 extrapolated to infinity (AUCinf) and the Cmax. Secondary objectives include assessment of the time to Cmax (tmax), AUC from time 0 to the last quantifiable concentration (AUClast) of Altebrel compared with Enbrel®, as well as evaluation of safety and tolerability. The safety endpoints of the trial are to evaluate the incidence of reported adverse effects, detecting changes in vital signs, clinical laboratory tests (hematologic, biochemistry, urine analysis and urine culture tests) and ECG.
Determination of sample size:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Provide written IC to participate in the trial and to comply with the trial procedures.
- •Take written informed consent to participate in the trial and to abide by the trial restrictions.
- •Be healthy male between the ages of 18 and 55 years. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, complete physical examination including blood pressure and heart rate measurement, 12 lead ECG and clinical laboratory tests.
- •Have a body mass index between 20.0 and 29.9kg/m², inclusive 5) Have Chest X ray with no evidence of current, active TB or previous (inactive) TB, general infections, heart failure, malignancy, or other clinically significant abnormalities taken at Screening or within 24 weeks prior to Day 1 and read by a qualified radiologist
排除标准
- •Being doubtful about their availability to complete the trial.
- •history and/or current presence of clinical significant atopic allergy, hypersensitivity or allergic reactions, also including known or suspected clinically relevant drug hypersensitivity to any components of the test and reference IMP formulation or comparable drugs.
- •Active or latent Tuberculosis or who have a history of Tuberculosis.
- •history of invasive systemic fungal infections or other opportunistic infections
- •systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process
- •serious infection associated with hospitalisation and/or which required intravenous antibiotics
- •history of and/or current cardiac disease
- •Have received live vaccine(s) within 30 days prior to Screening or who will require live vaccine(s) between Screening and the final study visit.
- •Intake medication with a half-life > 24 h within 1 month or 5 half-lives of the medication prior to the first administration of IMP.
- •Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody. A positive test for HIV antibody.
- •History of CNS demyelinating disorders in family (MS)
- •Have a history of smoking >10 cigarettes per day
研究组 & 干预措施
AryoGen Pharmed etanercept
Altebrel (etanercept prefilled syringe produced by AryoGen Pharmed Company) 25mg/0.5ml in prefilled syringe.
干预措施: Etanercept (Drug)
Pfizer etanercept
Enbrel® (etanercept prefilled syringe produced by Pfizer Company) 25mg/0.5ml in prefilled syringe.
干预措施: Etanercept (Drug)
结局指标
主要结局
Area under the concentration-time curve from time zero to infinity (AUCinf)
时间窗: 21 days
AUCinf will be calculated using the equation:AUCinf= AUClast + (Clast / Kel)
Maximum serum concentration (Cmax)
时间窗: 21 days
It is obtained directly from the observed concentration-time data
次要结局
- Area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast)(21 days)
- Time to Cmax (Tmax)(21 days)