Trial Outcomes & Findings for Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease (NCT NCT01410890)
NCT ID: NCT01410890
Last Updated: 2022-03-28
Results Overview
Cmax was defined as maximum observed plasma concentration.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
21 participants
Primary outcome timeframe
Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1
Results posted on
2022-03-28
Participant Flow
The study was conducted at 12 sites in 6 countries. A total of 27 participants were screened between 03-Nov-2014 and 23-Sep-2020, of whom 6 participants were screen failures and 21 participants were enrolled in the study.
Out of 21 participants, 1 participant signed the informed consent, but due to health status did not continue in the study to the treatment visit.
Participant milestones
| Measure |
Alglucosidase Alfa: <18 Years
Participants with less than (\<) 18 years of age received intravenous (IV) infusion of Alglucosidase alfa 20 milligram per kilogram (mg/kg) body weight on Day 1. Infusion was administered at an initial rate of approximately 1 milligrams 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.
|
Alglucosidase Alfa: >=18 Years
Participants with greater than or equal to (\>=) 18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
11
|
|
Overall Study
Treated
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Alglucosidase Alfa: <18 Years
Participants with less than (\<) 18 years of age received intravenous (IV) infusion of Alglucosidase alfa 20 milligram per kilogram (mg/kg) body weight on Day 1. Infusion was administered at an initial rate of approximately 1 milligrams 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.
|
Alglucosidase Alfa: >=18 Years
Participants with greater than or equal to (\>=) 18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
Baseline characteristics by cohort
| Measure |
Alglucosidase Alfa: <18 Years
n=10 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
5.1 years
STANDARD_DEVIATION 3.95 • n=99 Participants
|
41.8 years
STANDARD_DEVIATION 12.44 • n=107 Participants
|
23.4 years
STANDARD_DEVIATION 20.86 • n=206 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Anti-Recombinant Human Acid Alpha-Glucosidase (rhGAA) Immunoglobulin G (IgG) Antibody Status
Positive
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Anti-Recombinant Human Acid Alpha-Glucosidase (rhGAA) Immunoglobulin G (IgG) Antibody Status
Negative
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Anti-Recombinant Human Acid Alpha-Glucosidase (rhGAA) Immunoglobulin G (IgG) Antibody Status
Missing
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on all participants who received any amount of alglucosidase alfa.
Cmax was defined as maximum observed plasma concentration.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=10 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa
|
204000 nanograms per milliliter (ng/mL)
Standard Deviation 94600
|
307000 nanograms per milliliter (ng/mL)
Standard Deviation 143000
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on all participants who received any amount of alglucosidase alfa.
Tmax was defined as time to reach maximum observed plasma concentration.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=10 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa
|
4.23 hours
Interval 1.92 to 6.42
|
3.85 hours
Interval 1.42 to 5.33
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on all participants who received any amount of alglucosidase alfa.
AUC was defined as area under the plasma concentration-time curve from time 0 to 24 hours post-dose.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=10 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa
|
1110000 hours per nanograms per milliliter
Standard Deviation 753000
|
1890000 hours per nanograms per milliliter
Standard Deviation 969000
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on all participants who received any amount of alglucosidase alfa.
AUC0-last was defined as area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=10 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa
|
1040000 hours per nanograms per milliliter
Standard Deviation 590000
|
1840000 hours per nanograms per milliliter
Standard Deviation 901000
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on all participants who received any amount of alglucosidase alfa.
T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=10 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa
|
5.43 hours
Standard Deviation 3.82
|
3.84 hours
Standard Deviation 0.801
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on all participants who received any amount of alglucosidase alfa.
CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=10 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa
|
0.529 Liters per hour
Standard Deviation 0.613
|
1.26 Liters per hour
Standard Deviation 1.24
|
PRIMARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on all participants who received any amount of alglucosidase alfa.
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.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=10 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa
|
2.35 Liters
Standard Deviation 2.02
|
5.59 Liters
Standard Deviation 3.72
|
SECONDARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Cmax was defined as maximum observed plasma concentration.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=12 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=7 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants
|
256000 ng/mL
Standard Deviation 121000
|
262000 ng/mL
Standard Deviation 160000
|
SECONDARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.
Tmax was defined as time to reach maximum observed plasma concentration.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=12 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=7 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants
|
3.94 hours
Interval 1.92 to 5.27
|
4.33 hours
Interval 1.42 to 6.42
|
SECONDARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.
T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=12 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=7 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants
|
4.68 hours
Standard Deviation 2.95
|
4.79 hours
Standard Deviation 2.93
|
SECONDARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.
AUC0-last was defined as area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=12 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=7 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
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
|
1410000 hours per nanograms per milliliter
Standard Deviation 865000
|
1610000 hours per nanograms per milliliter
Standard Deviation 86800
|
SECONDARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.
AUC0-inf was defined as area under the concentration-time curve from time 0 extrapolated to infinite time.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=12 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=7 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
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
|
1450000 hours per nanograms per milliliter
Standard Deviation 941000
|
1700000 hours per nanograms per milliliter
Standard Deviation 985000
|
SECONDARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.
CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=12 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=7 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants
|
0.765 Liters per hour
Standard Deviation 0.518
|
1.21 Liters per hour
Standard Deviation 1.60
|
SECONDARY outcome
Timeframe: Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1Population: Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.
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.
Outcome measures
| Measure |
Alglucosidase Alfa: <18 Years
n=12 Participants
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=7 Participants
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants
|
5.82 Liters
Standard Deviation 6.49
|
7.26 Liters
Standard Deviation 9.16
|
Adverse Events
Alglucosidase Alfa: <18 Years
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Alglucosidase Alfa: >=18 Years
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Alglucosidase Alfa: <18 Years
n=10 participants at risk
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 participants at risk
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
Other adverse events
| Measure |
Alglucosidase Alfa: <18 Years
n=10 participants at risk
Participants with \<18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
Alglucosidase Alfa: >=18 Years
n=10 participants at risk
Participants with \>=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
|
|---|---|---|
|
Infections and infestations
Fungal Skin Infection
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Infections and infestations
Nasopharyngitis
|
20.0%
2/10 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Infections and infestations
Rhinitis
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Skin and subcutaneous tissue disorders
Papule
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
20.0%
2/10 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
General disorders
Fatigue
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
General disorders
Pyrexia
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Investigations
Blood Pressure Increased
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Investigations
Body Temperature Increased
|
10.0%
1/10 • Number of events 1 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/10 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
10.0%
1/10 • Number of events 2 • All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
- Publication restrictions are in place
Restriction type: OTHER