Trial Outcomes & Findings for Pharmacokinetic Study of ADVATE 3000 IU in Previously Treated Patients With Severe Hemophilia A (NCT NCT00916032)
NCT ID: NCT00916032
Last Updated: 2021-05-19
Results Overview
Computed using the linear trapezoidal method.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
29 participants
Primary outcome timeframe
Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.
Results posted on
2021-05-19
Participant Flow
Enrollment was conducted in Russia and Bulgaria at 4 clinical sites.
29 participants were enrolled. Six participants discontinued, (four were screen failures and two were withdrawn before randomization). Therefore 23 participants were randomized.
Participant milestones
| Measure |
Two 1500 IU Vials Then One 3000 IU Vial
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total) followed by one 3000 IU potency vial dissolved in 5 mL diluent.
|
One 3000 IU Vial Then Two 1500 IU Vials
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent followed by two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
11
|
|
Overall Study
COMPLETED
|
12
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetic Study of ADVATE 3000 IU in Previously Treated Patients With Severe Hemophilia A
Baseline characteristics by cohort
| Measure |
All Study Participants
n=23 Participants
Participants were randomized to receive via intravenous infusion 3000 International Units (IU) Advate using either one 3000 IU potency vial dissolved in 5 mL diluent followed by two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total) or the alternate sequence.
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|---|---|
|
Age, Continuous
|
36.5 years
STANDARD_DEVIATION 13.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
9 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
Computed using the linear trapezoidal method.
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUC 0-48h). Chromogenic Assay
|
1158 (IU·h)/dL
Standard Deviation 335
|
1264 (IU·h)/dL
Standard Deviation 364
|
PRIMARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
Computed using the linear trapezoidal method.
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUC 0-48h). One-stage Activated Partial Thromboplastin Time (aPTT) Assay
|
1129 (IU·h)/dL
Standard Deviation 310
|
1226 (IU·h)/dL
Standard Deviation 358
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
The total area under the plasma concentration versus time curve when the concentration is extrapolated to zero using the slope of the β-phase of the model.
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC 0-infinity). Chromogenic Assay
|
1267 (IU·h)/dL
Standard Deviation 395
|
1383 (IU·h)/dL
Standard Deviation 437
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
The total area under the plasma concentration versus time curve when the concentration is extrapolated to zero using the slope of the β-phase of the model.
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC 0-infinity). One-stage aPTT Assay
|
1235 (IU·h)/dL
Standard Deviation 364
|
1348 (IU·h)/dL
Standard Deviation 427
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3 hours.Population: Intent to Treat
Determined as the highest Factor VIII (FVIII) activity achieved post-infusion
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Incremental Recovery at Cmax - Chromogenic Assay
|
1.81 (IU/dL)/(IU/kg)
Standard Deviation 0.40
|
2.04 (IU/dL)/(IU/kg)
Standard Deviation 0.34
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3 hours.Population: Intent to Treat
Determined as the highest FVIII activity achieved post-infusion
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Incremental Recovery at Cmax - One-stage aPTT Assay
|
1.75 (IU/dL)/(IU/kg)
Standard Deviation 0.43
|
1.96 (IU/dL)/(IU/kg)
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: 30 minutes pre-infusion and 30 minutes post-infusionPopulation: Intent to Treat
Change in factor VIII concentration from pre-infusion to 30 minutes post-infusion
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Incremental Recovery at 30 Minutes- Chromogenic Assay
|
1.62 (IU/dL)/(IU/kg)
Standard Deviation 0.42
|
1.84 (IU/dL)/(IU/kg)
Standard Deviation 0.40
|
SECONDARY outcome
Timeframe: 30 minutes pre-infusion and 30 minutes post-infusionPopulation: Intent to Treat
Change in factor VIII concentration from pre-infusion to 30 minutes post-infusion
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Incremental Recovery at 30 Minutes- One-stage aPTT Assay
|
1.64 (IU/dL)/(IU/kg)
Standard Deviation 0.43
|
1.90 (IU/dL)/(IU/kg)
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.calculated as log\_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Elimination Phase Half-life- Chromogenic Assay
|
13.27 hour
Standard Deviation 4.05
|
12.84 hour
Standard Deviation 4.31
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.calculated as log\_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Elimination Phase Half-life- One-stage aPTT Assay
|
13.80 hour
Standard Deviation 3.95
|
13.50 hour
Standard Deviation 2.81
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
computed as the dose divided by total AUC
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
FVIII Clearance- Chromogenic Assay
|
4.57 mL/(kg·h)
Standard Deviation 1.75
|
3.99 mL/(kg·h)
Standard Deviation 1.53
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
Computed as the dose divided by total AUC
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
FVIII Clearance- One-stage aPTT Assay
|
4.66 mL/(kg·h)
Standard Deviation 1.81
|
4.06 mL/(kg·h)
Standard Deviation 1.46
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
Computed as total area under the first moment curve (Total AUMC) divided by the total area under the concentration versus time curve (Total AUC)
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Mean Residence Time (MRT)- Chromogenic Assay
|
17.02 hour
Standard Deviation 5.37
|
16.84 hour
Standard Deviation 5.81
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
Computed as total area under the first moment curve (Total AUMC) divided by the total area under the concentration versus time curve (Total AUC)
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Mean Residence Time (MRT)- One-stage aPTT Assay
|
16.95 hour
Standard Deviation 4.77
|
17.16 hour
Standard Deviation 4.65
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
computed as Clearance (CL) \* Mean residence time (MRT)
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Volume of Distribution at Steady State- Chromogenic Assay
|
0.72 dL/kg
Standard Deviation 0.23
|
0.61 dL/kg
Standard Deviation 0.13
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
computed as CL \* MRT
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Volume of Distribution at Steady State- One-stage aPTT Assay
|
0.74 dL/kg
Standard Deviation 0.19
|
0.64 dL/kg
Standard Deviation 0.11
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
Determined as the highest FVIII activity achieved post-infusion.
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Factor VIII (FVIII) Maximum Plasma Concentration (C-max)- Chromogenic Assay
|
94 IU/dL
Standard Deviation 21
|
101 IU/dL
Standard Deviation 18
|
SECONDARY outcome
Timeframe: Within 30 minutes prior to the start of the infusion; and after the end of the infusion at 15, 30 minutes, and 1, 3, 6, 9, 24, 28, 32, and 48 hours.Population: Intent to Treat
Determined as the highest FVIII activity achieved post-infusion.
Outcome measures
| Measure |
One 3000 International Unit (IU) Vial
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using one 3000 IU potency vial dissolved in 5 mL diluent
|
Two 1500 IU Vials
n=23 Participants
Participants received via intravenous (IV) infusion 3000 International Units (IU) Advate using two 1500 IU potency vials dissolved in 5 mL diluent each (administered in 10 mL diluent in total)
|
|---|---|---|
|
Factor VIII (FVIII) Maximum Plasma Concentration (C-max)- One-stage aPTT Assay
|
91 IU/dL
Standard Deviation 21
|
98 IU/dL
Standard Deviation 20
|
Adverse Events
One 3000 International Unit (IU) Vial
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Two 1500 IU Vials
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Baxter's agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication of the main/primary endpoint or ≤24 months after study completion. Baxter requires a review of results communications (e.g., for confidential information) prior to submission for publication, and shall review and if necessary amend the manuscript in ≤30 days
- Publication restrictions are in place
Restriction type: OTHER