Comparative Pharmacokinetic and Pharmacodynamic Study Between 2 Agalsidase Beta Formulations at a Single Dose of 1 mg/kg of Agalsidase (Biosidus) and Fabrazyme (Sanofi Genzyme) as Intravenous Infusion in Male Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum Serum Concentration of Agalsidase Beta (Cmax)
研究概览
简要总结
Pharmacokinetic/Pharmacodynamic Study of 2 agalsidase beta Formulations in Single Dose Administered to Healthy Volunteers as intravenous infusion, at a concentration of 1 mg/kg
详细描述
Volunteers will receive either one or the other agalsidase beta formulation. Drug will be administered as an intravenous 5h infusion. Plasma samples will be taken at different time points, from before infusion up to 12h later. Pharmacokinetic (PK) and pharmacodynamic (PD) profile will be determined, and bioequivalence evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Male subjects between the ages of 18 and 40
- •Body mass index (BMI) between 19 and 25 kg/m².
- •Volunteers whose complementary exams (ECG, chest X-ray, blood and urine, PCR for COVID-19), performed prior to their inclusion are within the normal range and/or are not clinically significant according to the investigator's judgement.
- •Subjects with systolic blood pressure higher than 110 mmHg and lower than 139 mmHg, diastolic blood pressure higher than 70 mmHg and lower than 89 mmHg with a heart rate higher than 50 and lower than 90 beats per minute after being seated for 5 minutes and, then, standing up (extreme values are included)
- •Volunteers who are well disposed to the study and have signed the approved informed consent prior to the start of the study
排除标准
- •History of clinically significant allergies (except for untreated asymptomatic seasonal allergies)
- •A drop of ≥ 20 mmHg of systolic blood pressure or ≥ 10 mmHg of diastolic blood pressure within the first 3 minutes after the postural change
- •Volunteers who are receiving other drugs (prescription or over-the-counter) or who have within the 2 weeks prior to the study
- •Volunteers with history of autoimmune diseases.
- •Chronic disorders of the CNS, psychological and/or psychiatric disorders: bipolar disorder, severe depression, insomnia, changes in personality
- •Active or chronic infections
- •Having received live or inactivated viral or bacterial vaccines, within the fifteen days prior to visits 1 or 2
- •For COVID vaccines, a 15 day window period prior to visits #1 or #2 must be respected. This period was taken from the recommendations published by the National Ministry of Health on May 29th
- •The volunteer will be able to receive the vaccine 35 days after receiving the investigational product.
- •Known allergies to any of the components of the formulations
- •Active smoker, of more than 10 cigarettes/day
- •Current clinical evidence of severe digestive disorders, surgeries of the gastrointestinal tract (except for appendectomy)
- •Current clinical evidence of kidney disease
- •Current clinical evidence of liver disorders
- •Current clinical evidence of respiratory and cardiac disease
- •Presence of diabetes mellitus, thyroid dysfunction or other endocrine disorders
- •Evidence of active gastroduodenal disease
- •History of peripheral thrombotic phenomena
- •Underlying neurological disease
- •Presence of a current progressive chronic disease
- •History of drug or alcohol abuse or addiction within the last three years
- •Participation in a clinical study within the last three months
- •Use of any drug within the fourteen days prior to the start of the study that, according to the principal investigator's judgement may interfere with the biodistribution of the medicinal product.
- •Subjects who have donated or suffered from blood loss within the twelve weeks prior to the start of the study, or intends to donate blood within the following three months after the completion of the study.
- •Excessive drinker of tea, cocoa, mate, coffee and/or caffeinated drinks (>5 cups/day) or of wine (>0.5 L/day) or alcohol (>50 ml/day)
- •Significant abnormalities in the electrocardiogram
- •Positive PCR test for COVID-19
- •Positive serology for HIV, hepatitis B or hepatitis C
- •Abnormal clinical laboratory test results (that according to the principal investigator's judgement are considered clinically significant)
- •Uncooperative volunteers
研究组 & 干预措施
Agalsidase Beta from Biosidus
Participants received a single infusion at a dose 1 mg/kg
干预措施: Agalsidase beta from Biosidus 1 mg/kg (Biological)
Fabrazyme (Sanofi-Genzyme)
Participants received a single infusion at a dose 1 mg/kg
干预措施: Fabrazyme (agalsidase beta) 1 mg/kg (Biological)
结局指标
主要结局
Maximum Serum Concentration of Agalsidase Beta (Cmax)
时间窗: 0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Compare the maximum serum concentration of two formulations of agalsidase beta after intravenous infusion of 1 mg/kg: * Fabrazyme (Sanofi-Genzyme) (Reference Formulation, "R") * Agalsidase beta from Biosidus SA (Test Formulation, "T")
Area Under the Curve of Serum Concentration Between Times 0 and 12 Hours of Agalsidase Beta
时间窗: 0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Compare the area under the curve between times 0 and 12 hours of two formulations of agalsidase beta after intravenous infusion of 1 mg/kg: * Fabrazyme (Sanofi-Genzyme) (Reference Formulation, "R") * Agalsidase beta from Biosidus SA (Test Formulation, "T")
Time at Which Maximum Serum Concentration of Agalsidase Beta is Observed (Tmax)
时间窗: 0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Compare the time at which maximum serum concentration of agalsidase beta is observed of two formulations of agalsidase beta after intravenous infusion of 1 mg/kg: * Fabrazyme (Sanofi-Genzyme) (Reference Formulation, "R") * Agalsidase beta from Biosidus SA (Test Formulation, "T")
Area Under the Curve of Serum Concentration, Resulting From the Extrapolation From Time 0 to Infinite Time
时间窗: 0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Compare the area under the curve of serum concentration, resulting from the extrapolation from time 0 to infinite time of two formulations of agalsidase beta after intravenous infusion of 1 mg/kg: * Fabrazyme (Sanofi-Genzyme) (Reference Formulation, "R") * Agalsidase beta from Biosidus SA (Test Formulation, "T")
次要结局
- Enzymatic Activity on Plasma Samples Measured With Fluorometric Method(Pre-infusion and 5 hours post administration (end of infusion))
- Number of Patients With Adverse Events(From infusion to 35 days after)
- Number of Participants With Positive Results for the Presence of Neutralizing Antibodies Against Agalsidase Beta(0 hours,12 hours and 35 days after the end of the infusion.)