A double blinded, balanced, randomized, single dose, parallel group, active-controlled study to compare the pharmacokinetics of the test product GBL19 (recombinant asparaginase, Gennova Biopharmaceuticals Ltd.) with the reference product Spectrila® (Medac GmbH) at 5000 IU/m2, in healthy, adult, subjects.
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- 1. Comparison of area under serum asparaginase activity (SAA) vs. time curves(AUC0-inf) for a single dose of the test and the reference product.
研究概览
简要总结
This clinical trial is a double-blinded, balanced, randomized, single-dose, parallel-group, active-controlled study to compare the pharmacokinetics of the test product GBL19 (recombinant asparaginase) with the reference product Spectrila® at 5000 IU/m2, in healthy, adult, subjects. The study will enroll 82 healthy participants. Subjects will be housed in the clinical facility unit a day before dosing. The sample will be collected at prespecified time points. Subjects will be under supervision for 96 hours in the CPU unit and subject vital and physical examination, and measurements (blood pressure, pulse rate, body temperature, and respiratory rate) will be monitored at defined periods. Safety laboratory parameters will be assessed on day 4, day 14 & day 30.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 20.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Willing to provide written informed consent for participation in the study, and able to comprehend the nature and purpose of the study.2.Willing to be available for the entire study period and to comply with the protocol requirements.3.Normal, healthy, adult, human subject of 20-45 years (both inclusive) of age.4.Body mass index in the range of 18.5 – 30.0 kg/m2 (both inclusive) with minimum of 50 kg weight.5.Normal health status as determined by baseline medical and medication history, at the time of screening and vital signs measurements and physical examination at the time of screening as well as check-in.6.Normal or clinically non-significant laboratory values as determined by haematological, biochemistry tests (serum ALP, serum creatinine, SGOT/AST, SGPT/ALT, serum uric acid; serum bilirubin–total, direct and indirect; total proteins, serum albumin, serum blood urea nitrogen, triglycerides, cholesterol-total, random blood glucose, aPTT, PT, serum amylase, serum lipase) and urine analysis.7.Normal or clinically non-significant 12-lead ECG recording.8.Non-smokers or subjects who have no history of smoking for the last one year prior to check-in.9.Subjects who are willing to abstain from chewing any tobacco containing products at least 72.00 hours prior to check-in and throughout the study.10.Willing to abstain from alcohol or alcoholic products at least 24.00 hours prior to check-in until last sample collection.11.Willing to abstain from xanthine or its derivative containing food or beverages (e.g. chocolates, tea, coffee or cola drinks) and flavonoid containing products at least 48.00 hours prior to check-in until last sample collection.12.Willing to abstain from grapefruit or its juice at least 72.00 hours prior to check-in until last sample collection.13.For male subjects: Subjects willing to use adequate contraception during sexual intercourse with female partners of childbearing potential during the study and for a period of 3 months after receiving last dose of IP.14.For female subjects:Negative urine pregnancy test during screening and negative serum hCG test at the time of check-in.Female subjects with childbearing potential or those within their first two years of onset of menopausal syndrome willing to either abstain from sexual intercourse, or should use acceptable birth control methods for at least 15 days before check-in till 3 months post last-dose.
- •[Acceptable birth control methods include barrier methods such as diaphragm/condom with or without spermicide or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy has been performed)].
排除标准
- •1.Any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract and of blood forming organs. 2.Significant history or current evidence of malignancy or chronic.
- •infectious, cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic (endocrine), haematological, gastrointestinal, dermatological, immunological, or psychiatric diseases, or organ dysfunction. 3.Any major illness or hospitalized within 90 days prior to check-in. 4.Requiring medication for any ailment having enzyme-modifying activity within one month prior to check-in and throughout the study. 5.Use of any depot injection or an implant of any drug within 3 months prior to check-in and throughout the study. 6.Use of any prescribed medication (including herbal medicines and vitamin supplements) or OTC products within 30 days prior to check-in and throughout the study; history or presence of significant gastric and/or duodenal ulceration. 7.Consumption of St John’s Wort within 14 days prior to check in and throughout the study. 8.Suffering from pancreatitis (inflammation of the pancreas). 9.Pre-existing known coagulopathy. 10.Difficulty in swallowing tablets or capsules. 11.Use of any recreational drug or history of drug addiction. 12.Participated in any clinical investigation requiring repeated blood sampling or have donated blood in past 180 days prior to check-in. 13.Positive urine alcohol and urine drug of abuse tests during check-in. 14.Reactive test for Human Immunodeficiency Virus (HIV) type I/II antibodies or Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibodies. 15.Lactating or nursing female subjects. 16.Female subjects using hormonal contraceptive (oral/implants). 17.History of allergy or hypersensitivity intolerance to asparaginase or its formulation excipients which, in the opinion of a clinical investigator, would compromise the safety of the subject or the study. 18.History of difficulty in accessibility of veins in arms.
结局指标
主要结局
1. Comparison of area under serum asparaginase activity (SAA) vs. time curves(AUC0-inf) for a single dose of the test and the reference product.
时间窗: 1. Pre-dose (within 2.00 hours before dosing), 0.00 (immediately after infusion), 0.50, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 12.00, 24.00, 48.00, 72.00 and 96.00 hours post-dose. | 2. Pre-dose (within 2.00 hours before dosing),0.00 (immediately after infusion), 0.50, 1.00, 1.50,2.00, 3.00, 4.00, 6.00, 8.00, 12.00, 24.00, 48.00, 72.00 and 96.00 hours post-dose.
2. Comparison of Cmax of SAA between the test and the reference group.
时间窗: 1. Pre-dose (within 2.00 hours before dosing), 0.00 (immediately after infusion), 0.50, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 12.00, 24.00, 48.00, 72.00 and 96.00 hours post-dose. | 2. Pre-dose (within 2.00 hours before dosing),0.00 (immediately after infusion), 0.50, 1.00, 1.50,2.00, 3.00, 4.00, 6.00, 8.00, 12.00, 24.00, 48.00, 72.00 and 96.00 hours post-dose.
次要结局
- 1. Area under SAA vs. time curves (AUC0-t).
- Depletion of mean asparagine levels in plasma.(From pre-dose to 96 hours post-dose.)
- 1. Incidence of adverse events after administration of the test & the reference product.
- Anti-drug antibodies (ADA).(Pre-dose, Day 14 & Day 30.)
研究者
Dr Priyesh Katara
Citus Research LLP