Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
- Conditions
- Pompe DiseaseGlycogen Storage Disease Type II (GSD II)
- Interventions
- Biological: alglucosidase alfa
- Registration Number
- NCT01410890
- Lead Sponsor
- Genzyme, a Sanofi Company
- Brief Summary
* 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Alglucosidase alfa alglucosidase alfa Participants received intravenous (IV) infusion of Alglucosidase alfa 20 milligrams per kilogram (mg/kg) body weight on Day 1. Infusion was administered at an initial rate of approximately 1 milligram per kilogram per hour (mg/kg/hr) with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of infusion-associated reactions (IARs), until a maximum rate of approximately 7 mg/kg/hr was reached.
- Primary Outcome Measures
Name Time Method Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa 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 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 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 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 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 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 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.
- Secondary Outcome Measures
Name Time Method 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 AUC0-last was defined as area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
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 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.
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 Cmax was defined as maximum observed plasma concentration.
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 AUC0-inf was defined as area under the concentration-time curve from time 0 extrapolated to infinite time.
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 Tmax was defined as time to reach maximum observed plasma concentration.
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 T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
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 CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Trial Locations
- Locations (12)
Investigational Site Number 1028
🇧🇬Sofia, Bulgaria
Investigational Site Number 356001
🇮🇳New Delhi, India
Investigational Site Number 356002
🇮🇳Vellore, India
Investigational Site Number 643001
🇷🇺Moscow, Russian Federation
Investigational Site Number 643002
🇷🇺Moscow, Russian Federation
Investigational Site Number 804001
🇺🇦Kiev, Ukraine
Investigational Site Number 826002
🇬🇧Salford, United Kingdom
Investigational Site Number 826003
🇬🇧Birmingham, United Kingdom
Investigational Site Number 840005
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 840008
🇺🇸Valhalla, New York, United States
Investigational Site Number 840007
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840003
🇺🇸Fairfax, Virginia, United States