A double-blind, randomised, single dose, single-centre, parallel group, two arm, comparative pharmacokinetic study of 420 mg intravenous solution for infusion of a Pertuzumab biosimilar candidate (AQ11) versus reference medicinal product (Perjeta®) in healthy, adult, male human subjects under fasting condition.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- To evaluate pharmacokinetic characteristics of two formulations of Pertuzumab
研究概览
简要总结
Discussion of the Study Design
i. Choice of Dose: The dose of Pertuzumab 420 mg concentrate for solution for infusion is chosen to achieve sufficient serum levels to characterize the pharmacokinetic profile of the drug.
ii. Duration of sampling:Sampling duration of 2016.00 hours is considered sufficient for adequate pharmacokinetic profiling of analyte.
iii. Design; Parallel design has been selected due to long half-life and pharmacokinetic study.
iv. Study Condition: The present study will be conducted under fasting condition based on the EMA guideline (GUIDELINE ON THE INVESTIGATION OF BIOEQUIVALENCE), In general, a bioequivalence study should be conducted under fasting conditions as this is considered to be the most sensitive condition to detect a potential difference between formulations.
v. Choice of volunteers: The healthy adult volunteers will consititute the study population. The choice and suitability of this population is discussed below.
This selection of healthy volunteers is regarded as adequate in most instances to allow extrapolation of the results to populations. Opting for healthy subjects is in accordance with EMA guideline and previous similar studies. As it is stated in the EMA guideline, GUIDELINE ON THE INVESTIGATION OF BIOEQUIVALENCE: “the subject population for bioequivalence studies should be selected with the aim of permitting detection of differences between pharmaceutical products. In order to reduce variability not related to differences between products, the studies should normally be performed in healthy volunteers unless the drug carries safety concerns that make this unethical. This model, in vivo healthy volunteers, is regarded as adequate in most instances to detect formulation differences and to allow extrapolation of the results to populations for which the reference medicinal product is approved.
Also, in another EMA guideline specifically developed for monoclonal antibodies such as Pertuzumab (Guideline on similar biological medicinal products containing monoclonal antibodies – non-clinical and clinical issues), healthy subjects are the first choice for PK studies: “Healthy volunteers are likely to have less variability in PK as target-mediated clearance may be less important than in patients.
As this is a pharmacokinetic study, the subject population of healthy volunteers is selected with the aim to minimize the variability and permit detection of differences between the two pharmaceutical products.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- Male
入选标准
- •1 Healthy male human subjects, age in the range of 18 – 45 years both inclusive 2 Body Mass Index between 18.5-30 Kg / m2 extremes included and Body weight is at least 50 kg 3 Subjects with normal findings as determined by baseline history, physical examination and vital sign examination (blood pressure, pulse rate, respiration rate and body temperature).
- •4 Subjects with clinically acceptable findings as determined by haemogram, biochemistry, urinalysis, 12 lead ECG and chest X-ray (if done).
- •5 Willingness to follow the protocol requirements especially abstaining from xanthine containing food or beverages (chocolates, tea, coffee or cola drinks) or grapefruit juice, any alcoholic products, the use of cigarettes and the use of tobacco products for 48.00 hours prior to dosing until after the last blood sample collection in the study and adherence to food, fluid and posture restrictions.
- •6 Subjects willing to sign Informed Consent Form.
- •7 Subjects with Left ventricular ejection fraction (LVEF) ≥ 55 %.
- •8 Ability to comply with study and follow-up procedures.
- •9 Subjects who have no evidence of underlying disease during screening medical history.
- •10 No history of significant alcoholism.
- •11 No history of drug abuse (benzodiazepines and barbiturates) for the last one month and other illegal drugs (Appendix B) for the last 06 months.
- •12 Non-smokers, ex-smokers and moderate smokers will be included.
- •â€œModerate smokers are defined as someone smoking 10 cigarettes or less per day, ex-smokers are someone who completely stopped smoking for at least 3 months.â€.
排除标准
- •1 Known history of hypersensitivity to Pertuzumab or any of the excipients and/or related drugs.
- •2 Requiring medication for any ailment having enzyme-modifying activity in the previous 28 days, prior to dosing day.
- •3 Subjects who have taken prescription medications or over-the-counter products (excluding vitamins, mineral supplements, and dietary supplements) within 28 days prior to administration of IMP.
- •4 Any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract, blood–forming organs, use of monoclonal antibody etc.
- •5 History of cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic, haematological, gastrointestinal, endocrine, immunological or psychiatric diseases.
- •6 Participation in a clinical drug study or bioequivalence study 90 days prior to dosing of the present study.
- •7 History of malignancy or other serious diseases.
- •8 Blood donation 90 days prior to dosing of the present study.
- •9 Subjects with positive HIV tests, HBsAg or Hepatitis-C tests.
- •10 Subjects with any other medical or psychiatric condition that could compromise study participation.
- •11 Found positive in breath alcohol test.
- •12 Found positive in urine test for drug abuse.
- •13 Any contraindication to blood sampling.
- •14 Male subjects not confirming to using birth control measures, from the date of screening until the completion of the study.
- •Abstinence, barrier methods (condom etc.) are acceptable.
- •15 Major surgery or trauma within past one year of screening or anticipated need for any surgery during the study.
- •16 Any other condition or circumstance that, in the judgment of the Investigator, might increase the risk to the subject or decrease the chance of obtaining satisfactory data to achieve the objectives of the study.
结局指标
主要结局
To evaluate pharmacokinetic characteristics of two formulations of Pertuzumab
时间窗: Pre dose (collected within 01.00 hour prior to dosing), 60 min (prior to end of infusion) & at 02.00, 03.00, 06.00, & 12.00 hours post-dose, Day 2, 3, 5, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 post dose
次要结局
- To evaluate the safety parameters of two formulations of Pertuzumab(Well-being assessment, blood pressure & pulse rate at 01.00, 03.00, 05.00, 08.00, 12.00 and 24.00 hrs ± 45 minutes of scheduled time.)