A Phase 3/4 Prospective Study to Characterize the Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 21
- 试验地点
- 24
- 主要终点
- Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa
研究概览
简要总结
- The primary objective of this study was to characterize the pharmacokinetics (PK) of alglucosidase alfa manufactured at the 4000 L scale in participants who had a confirmed diagnosis of Pompe disease.
- A secondary objective of this study was to evaluate and explore the relationship between anti-recombinant human acid alpha-glucosidase antibody titers and the PK of alglucosidase alfa.
详细描述
The total study duration per participant was 4 to 8 weeks that consisted of a screening period (from 2 days to 4 weeks), treatment visit (1 day), and a follow up call (greater than or equal to 30 days). Two participants enrolled prior to protocol amendment 2 (dated 17 December 2015), which changed the study to single-dose, and were treated for 26 weeks, with a 4-week follow up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A participant was to meet all of the following criteria to be eligible for this study:
- •The participant and/or the participant's parent/legal guardian was willing and able to provide signed informed consent.
- •The participant had a confirmed acid alpha-glucosidase (GAA) enzyme deficiency from skin, blood, or muscle tissue and/or 2 confirmed GAA gene mutations.
- •Infant and toddler Pompe disease participants could be included in the study only under condition (minimal body weight) that the trial-related blood loss (including any losses in the maneuver) would not exceed 3 percent (%) of the total blood volume during a period of 4 weeks and would not exceed 1 % at any single time.
- •The participant, if female and of childbearing potential, must have had a negative pregnancy test (urine beta-human chorionic gonadotropin) at screening. Note: All female participants of childbearing potential and sexually mature males must have agreed to use a medically accepted method of contraception throughout the study.
- •For participants previously treated with alglucosidase alfa the participant had received alglucosidase alfa for at least 6 months.
排除标准
- •A participant who met any of the following criteria was excluded from this study:
- •The participant was participating in another clinical study using an investigational product.
- •The participant, in the opinion of the Investigator, was unable to adhere to the requirements of the study.
- •The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
结局指标
主要结局
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa
时间窗: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Cmax was defined as maximum observed plasma concentration.
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa
时间窗: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
AUC0-last was defined as area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa
时间窗: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Tmax was defined as time to reach maximum observed plasma concentration.
Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa
时间窗: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa
时间窗: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
AUC was defined as area under the plasma concentration-time curve from time 0 to 24 hours post-dose.
Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa
时间窗: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa
时间窗: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.
次要结局
- Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants(Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1)
- Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants(Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1)
- Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants(Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1)
- Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 and Extrapolated to Infinite Time (AUC0-inf) in Anti-rhGAA Antibody Positive and Negative Participants(Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1)
- Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants(Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1)
- Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants(Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1)
- Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants(Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1)