Demonstration of Pharmacodynamic Equivalence of Enoxaparin Rovi (100-mg Subcutaneous Injection) to Clexane® (100-mg Subcutaneous Injection) in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 主要终点
- AUEC0-inf for anti-FXa
研究概览
简要总结
To demonstrate the pharmacodynamic (PD) equivalence of enoxaparin Rovi (100 mg/mL) 100-mg SC injection to Clexane® (100 mg/mL) 100-mg SC injection in healthy volunteers.
As secondary objective, to evaluate the safety and tolerability of enoxaparin Rovi (100 mg/mL) in healthy volunteers.
详细描述
This is a single-dose, randomized, double-blind, 2-period, 2 sequence crossover study. Subjects will be screened up to 30 days before the study begins and admitted to the clinic on Day -1 of Period 1 for baseline assessments. Before dosing on Day 1 of Period 1, subjects will be randomly assigned to a treatment sequence. Subjects will receive a single dose of study drug on Day 1 of each treatment period.
On Day 1 of Period 1, subjects will receive a single dose by subcutaneous route of the assigned study drug: enoxaparin (100 mg/mL) 100-mg SC injection manufactured by Rovi Spain, or Clexane (100 mg/mL) 100-mg SC injection manufactured by Sanofi EU; after an overnight fasting period of at least 10 hours. Subjects will continue fasting for at least 4 hours after study drug administration.
The washout period between administrations of study drug in each period will be at least 7 days.
On Day 1 of Period 2, subjects will cross over to receive the dose of the other drug, after an overnight fasting period of at least 10 hours. The total duration of the study will be approximately 6 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This study will be double blinded in that the subjects and laboratories will be blinded. While the enoxaparin (manufactured by Rovi, Spain) and Clexane (manufactured by Sanofi, EU) solutions for SC injection may be identical in appearance, the prefilled syringes for both study drugs may not be identical. Therefore, the unblinded pharmacist will be responsible for dispensing the study drug in a manner consistent with maintaining the blind and a dedicated unblinded team member will perform study drug administration.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject provides informed consent (approved by an Independent Ethical Committee (IEC)) before any study specific evaluation is performed.
- •Subject is between the ages of 18 and 45 years, inclusive.
- •All female subjects must have a negative pregnancy test at Screening and upon check-in to the clinic.
- •Women of childbearing potential must use or have used one of the following acceptable birth control methods: Surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) for at least 6 months before the first dose of study drug;Intrauterine device in place for at least 3 months before the first dose of study drug; or barrier method (condom, diaphragm) for at least 21 days before the first dose of study drug and throughout the study.
- •Subject has a body mass index between 18 and 30 kg/m2, inclusive.
- •Subject is able and willing to abstain from alcohol from 48 hours before the first dose of study drug through the end of the study.
- •Subject has no clinically significant abnormalities in medical history, vital sign measurements, or physical examination findings.
- •Subject has computerized 12-lead electrocardiogram (ECG) results showing no signs of clinically relevant pathology or deviations, as judged by the investigator.
- •Subject has hematology, serum chemistry, coagulation, and urinalysis test results within the reference ranges (Hb ≥7.5 mmol/L and ≥8.5 mmol/L for female and male, respectively) or showing no clinically relevant deviations, as judged by the investigator. Thrombocytes at screening have to be within the normal range.
- •Subject is a nonsmoker or has quit smoking at least 6 months before the first dose of study drug.
排除标准
- •Subjects are excluded from the study if any of the following criteria are met:
- •Subject has active or recurring clinically significant skin, head, ears, eyes, nose, throat, respiratory, cardiovascular, gastrointestinal, endocrine/metabolic, genitourinary, neurologic, hematologic, musculoskeletal, immunologic, allergic, psychological/psychiatric, or other disease requiring medical treatment.
- •Female subject with weight < 45 kg or male subject with weight < 57 kg.
- •Subject is a woman who is pregnant or breastfeeding.
- •Subject has systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 90 mm Hg at Screening (confirmed upon repeat measurement).
- •Subject has a calculated (Cockroft & Gault formula) creatinine clearance less than 80 mL/minute and the value does not return to within reference range upon retest.
- •Subject has Hb <7.5 mmol/L and <8.5 mmol/L for female and male, respectively.
- •Subject has an active malignancy of any type other than nonmelanomatous skin malignancies.
- •Subject has any history of alcohol abuse or drug addiction.
- •Subject has any history of relevant drug and/or food allergies.
- •Subject has used an investigational drug within 60 days before the first dose of study drug.
- •Subject has used any prescription drugs (with special attention to antiplatelet or anticoagulant medication, eg, acetyl salicylic acid, NSADs, clopidogrel, warfarin, acenocumarol, heparin, low molecular weight heparin, dabigatran, rivaroxaban, apixaban) or over-the-counter medication that may affect coagulation (including aspirin or NSAIDs) within 4 weeks before dosing, or any other over-the-counter medication (including vitamins, herbal supplements, or dietary supplements) within 2 weeks before dosing.
- •Subject has donated or lost 550 mL or more of blood (including plasmapheresis) within 60 days before the first dose of study drug.
- •Subject has a positive test result for drugs of abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, oxycodone), cotinine, or alcohol.
- •Subject has a positive test result for human immunodeficiency virus (1 or 2) antibody, hepatitis B surface antigen, or hepatitis C virus antibody.
- •Subject has any illness within 5 days before the first dose of study drug.
- •Subject has a positive test for fecal occult blood at Screening.
- •Subject has any history and/or current conditions of bleeding tendency such as: active bleeding, known bleeding diathesis or hemostatic defects due to severe hepatic or renal disease; recent gastrointestinal or genitourinary bleeding (10 days before study entry) women of child-bearing potential with normal cyclic bleeding which is not considered as heavy menstruation by the investigator, are allowed for inclusion; diabetic hemorrhagic retinopathy, or other hemorrhagic ophthalmic conditions.
- •Subject has a known history or family history of any relevant congenital or acquired coagulation disorder (eg, hemophilia, von Willebrand-Jürgens syndrome, or activated protein C resistance based upon Factor V Leiden mutation).
- •Subject has a history of thrombocytopenia, including heparin induced thrombocytopenia.
- •Subject has a known history of hypersensitivity to drugs with a similar chemical structure to enoxaparin sodium (eg, unfractionated heparin, low molecular weight heparin) or to pork products.
- •Subject is a member of the professional or ancillary personnel involved in the study.
- •Subject is deemed not suitable for entry into the study in the opinion of the investigator.
研究组 & 干预措施
AB treatment sequence
Period 1-Test Treatment A: enoxaparin (100 mg/mL) 100-mg SC injection, manufactured by Rovi (Spain) Period 2-Reference Treatment B: Clexane (100 mg/mL) 100-mg SC injection, manufactured by Sanofi (EU)
干预措施: Enoxaparin (Drug)
AB treatment sequence
Period 1-Test Treatment A: enoxaparin (100 mg/mL) 100-mg SC injection, manufactured by Rovi (Spain) Period 2-Reference Treatment B: Clexane (100 mg/mL) 100-mg SC injection, manufactured by Sanofi (EU)
干预措施: Clexane (Drug)
BA treatment sequence
Period 1-Reference Treatment B: Clexane (100 mg/mL) 100-mg SC injection, manufactured by Sanofi (EU) Period 2-Test Treatment A: enoxaparin (100 mg/mL) 100-mg SC injection, manufactured by Rovi (Spain)
干预措施: Enoxaparin (Drug)
BA treatment sequence
Period 1-Reference Treatment B: Clexane (100 mg/mL) 100-mg SC injection, manufactured by Sanofi (EU) Period 2-Test Treatment A: enoxaparin (100 mg/mL) 100-mg SC injection, manufactured by Rovi (Spain)
干预措施: Clexane (Drug)
结局指标
主要结局
AUEC0-inf for anti-FXa
时间窗: Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)
area under the effect curve (AUEC) from time 0 to infinity, for anti-FXa
Amax for anti-FXa and anti-FIIa
时间窗: Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)
peak effect for anti-FXa activity (anti-FXamax), and anti-FIIa activity (anti-FIIamax)
AUEC0-T for anti-FXa and anti-FIIa
时间窗: Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2)
area under the effect curve (AUEC) from time 0 to the last measured activity (T), for anti-FXa and anti-FIIa
次要结局
- CL/F for anti-FXa and anti-FIIa(Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2))
- MRT for anti-FXa and anti-FIIa(Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2))
- Adverse Events (AEs)(from Informed Consent signature until 14 days after the last study drug administration (independently of the period))
- Serum chemistry(at Screening, Day -1 (Period 1 only), and Day 3 (Period 2 only) and at the follow up visit (Day 7 of Period 2 only))
- Blood presure(at Screening, Day -1 (Period 1 only), and before dosing (Pre-dose) and 0.5 hours after dosing on Day 1 (Periods 1 and 2))
- Pulse rate(at Screening, Day -1 (Period 1 only), and before dosing (Pre-dose) and 0.5 hours after dosing on Day 1 (Periods 1 and 2))
- Tympanic temperature(at Screening, Day -1 (Period 1 only), and before dosing (Pre-dose) and 0.5 hours after dosing on Day 1 (Periods 1 and 2))
- Urianalysis(at Screening, Day -1 (Period 1 only), and Day 3 (Period 2 only) and at the follow up visit (Day 7 of Period 2 only))
- hematology(at Screening, Day -1 (Period 1 only), and Day 3 (Period 2 only) and at the follow up visit (Day 7 of Period 2 only))
- Coagulation(at Screening, Day -1 (Period 1 only), and Day 3 (Period 2 only) and at the follow up visit (Day 7 of Period 2 only))
- Respiratory rate(at Screening, Day -1 (Period 1 only), and before dosing (Pre-dose) and 0.5 hours after dosing on Day 1 (Periods 1 and 2))
- AUEC0-T for TFPI levels(Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2))
- AUEC0-inf for TFPI levels(Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2))
- RAUEC(Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2))
- Amax for TFPI levels(Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2))
- Tmax for anti-FXa and anti-FIIa(Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2))
- t1/2 for anti-FXa and anti-FIIa(Day -1 (Periods 1 and 2), before dosing (Pre-dose), and between 0.5 and 36 hours after dosing on Day 1 (Periods 1 and 2))