Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2008-007347-13 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The objective of this clinical study is to compare the pharmacokinetic parameters of 3000 IU Advate using one 3000 IU potency vial dissolved in 5 mL diluent with that of 3000 IU Advate using two vials of 1500 IU potency dissolved in 5 mL diluent each (administered in 10 mL diluent in total) in previously treated patients with severe hemophilia A (factor VIII level < 1%).
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | One infusion using a 3000 IU potency vial of Advate dissolved and administered in 5 mL diluent followed by a second infusion of two 1500 IU potency vials of Advate dissolved in 5 mL diluent each (administered in 10 mL diluent in total) |
|
| 2 | Active Comparator | One infusion of two 1500 IU potency vials of Advate dissolved in 5 mL diluent each (administered in 10 mL diluent in total) followed by a second infusion of one 3000 IU potency vial of Advate dissolved and administered in 5 mL diluent |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Octocog alfa (recombinant human coagulation factor VIII) [ADVATE] | Biological | Participants will receive 3000 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) or the alternate sequence |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUC 0-48h). Chromogenic Assay | Computed using the linear trapezoidal method. | 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. |
| Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUC 0-48h). One-stage Activated Partial Thromboplastin Time (aPTT) Assay | Computed using the linear trapezoidal method. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC 0-infinity). Chromogenic Assay | 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. | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sofia | 1233 | Bulgaria | ||||
29 participants were enrolled. Six participants discontinued, (four were screen failures and two were withdrawn before randomization). Therefore 23 participants were randomized.
Enrollment was conducted in Russia and Bulgaria at 4 clinical sites.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Study 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUC 0-48h). Chromogenic Assay | Computed using the linear trapezoidal method. | Intent to Treat | Posted | Mean | Standard Deviation | (IU·h)/dL | 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. |
|
Throughout the study period, approximately 10 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | One 3000 International Unit (IU) Vial |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
Not provided
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C078147 | F8 protein, human |
| D005169 | Factor VIII |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC 0-infinity). One-stage aPTT Assay | 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. | 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. |
| Incremental Recovery at Cmax - Chromogenic Assay | Determined as the highest Factor VIII (FVIII) activity achieved post-infusion | 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. |
| Incremental Recovery at Cmax - One-stage aPTT Assay | Determined as the highest FVIII activity achieved post-infusion | 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. |
| Incremental Recovery at 30 Minutes- Chromogenic Assay | Change in factor VIII concentration from pre-infusion to 30 minutes post-infusion | 30 minutes pre-infusion and 30 minutes post-infusion |
| Incremental Recovery at 30 Minutes- One-stage aPTT Assay | Change in factor VIII concentration from pre-infusion to 30 minutes post-infusion | 30 minutes pre-infusion and 30 minutes post-infusion |
| Elimination Phase Half-life- Chromogenic Assay | calculated as log_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model | 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. |
| Elimination Phase Half-life- One-stage aPTT Assay | calculated as log_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model | 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. |
| FVIII Clearance- Chromogenic Assay | computed as the dose divided by total AUC | 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. |
| FVIII Clearance- One-stage aPTT Assay | Computed as the dose divided by total AUC | 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. |
| Mean Residence Time (MRT)- Chromogenic Assay | Computed as total area under the first moment curve (Total AUMC) divided by the total area under the concentration versus time curve (Total AUC) | 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. |
| Mean Residence Time (MRT)- One-stage aPTT Assay | Computed as total area under the first moment curve (Total AUMC) divided by the total area under the concentration versus time curve (Total AUC) | 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. |
| Volume of Distribution at Steady State- Chromogenic Assay | computed as Clearance (CL) * Mean residence time (MRT) | 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. |
| Volume of Distribution at Steady State- One-stage aPTT Assay | computed as CL * MRT | 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. |
| Factor VIII (FVIII) Maximum Plasma Concentration (C-max)- Chromogenic Assay | Determined as the highest FVIII activity achieved post-infusion. | 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. |
| Factor VIII (FVIII) Maximum Plasma Concentration (C-max)- One-stage aPTT Assay | Determined as the highest FVIII activity achieved post-infusion. | 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. |
| Kirov |
| Russia |
| Moscow | 125167 | Russia |
| Saint Petersburg | 195213 | Russia |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
|
| Primary | Area Under the Plasma Concentration Versus Time Curve From 0 to 48 Hours (AUC 0-48h). One-stage Activated Partial Thromboplastin Time (aPTT) Assay | Computed using the linear trapezoidal method. | Intent to Treat | Posted | Mean | Standard Deviation | (IU·h)/dL | 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. |
|
|
|
|
| Secondary | Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC 0-infinity). Chromogenic Assay | 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. | Intent to Treat | Posted | Mean | Standard Deviation | (IU·h)/dL | 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. |
|
|
|
| Secondary | Area Under the Plasma Concentration Versus Time Curve From 0 to Infinity (AUC 0-infinity). One-stage aPTT Assay | 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. | Intent to Treat | Posted | Mean | Standard Deviation | (IU·h)/dL | 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. |
|
|
|
| Secondary | Incremental Recovery at Cmax - Chromogenic Assay | Determined as the highest Factor VIII (FVIII) activity achieved post-infusion | Intent to Treat | Posted | Mean | Standard Deviation | (IU/dL)/(IU/kg) | 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. |
|
|
|
| Secondary | Incremental Recovery at Cmax - One-stage aPTT Assay | Determined as the highest FVIII activity achieved post-infusion | Intent to Treat | Posted | Mean | Standard Deviation | (IU/dL)/(IU/kg) | 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. |
|
|
|
| Secondary | Incremental Recovery at 30 Minutes- Chromogenic Assay | Change in factor VIII concentration from pre-infusion to 30 minutes post-infusion | Intent to Treat | Posted | Mean | Standard Deviation | (IU/dL)/(IU/kg) | 30 minutes pre-infusion and 30 minutes post-infusion |
|
|
|
| Secondary | Incremental Recovery at 30 Minutes- One-stage aPTT Assay | Change in factor VIII concentration from pre-infusion to 30 minutes post-infusion | Intent to Treat | Posted | Mean | Standard Deviation | (IU/dL)/(IU/kg) | 30 minutes pre-infusion and 30 minutes post-infusion |
|
|
|
| Secondary | Elimination Phase Half-life- Chromogenic Assay | calculated as log_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model | Posted | Mean | Standard Deviation | hour | 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. |
|
|
|
| Secondary | Elimination Phase Half-life- One-stage aPTT Assay | calculated as log_e2/λ, where λ is the regression slope in the terminal phase of the least absolute deviations regression model | Posted | Mean | Standard Deviation | hour | 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. |
|
|
|
| Secondary | FVIII Clearance- Chromogenic Assay | computed as the dose divided by total AUC | Intent to Treat | Posted | Mean | Standard Deviation | mL/(kg·h) | 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. |
|
|
|
| Secondary | FVIII Clearance- One-stage aPTT Assay | Computed as the dose divided by total AUC | Intent to Treat | Posted | Mean | Standard Deviation | mL/(kg·h) | 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. |
|
|
|
| Secondary | Mean Residence Time (MRT)- Chromogenic Assay | Computed as total area under the first moment curve (Total AUMC) divided by the total area under the concentration versus time curve (Total AUC) | Intent to Treat | Posted | Mean | Standard Deviation | hour | 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. |
|
|
|
| Secondary | Mean Residence Time (MRT)- One-stage aPTT Assay | Computed as total area under the first moment curve (Total AUMC) divided by the total area under the concentration versus time curve (Total AUC) | Intent to Treat | Posted | Mean | Standard Deviation | hour | 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. |
|
|
|
| Secondary | Volume of Distribution at Steady State- Chromogenic Assay | computed as Clearance (CL) * Mean residence time (MRT) | Intent to Treat | Posted | Mean | Standard Deviation | dL/kg | 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. |
|
|
|
| Secondary | Volume of Distribution at Steady State- One-stage aPTT Assay | computed as CL * MRT | Intent to Treat | Posted | Mean | Standard Deviation | dL/kg | 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. |
|
|
|
| Secondary | Factor VIII (FVIII) Maximum Plasma Concentration (C-max)- Chromogenic Assay | Determined as the highest FVIII activity achieved post-infusion. | Intent to Treat | Posted | Mean | Standard Deviation | IU/dL | 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. |
|
|
|
| Secondary | Factor VIII (FVIII) Maximum Plasma Concentration (C-max)- One-stage aPTT Assay | Determined as the highest FVIII activity achieved post-infusion. | Intent to Treat | Posted | Mean | Standard Deviation | IU/dL | 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. |
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| EG001 | Two 1500 IU Vials | 0 | 23 | 0 | 23 |
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
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D011498 |
| Protein Precursors |
| D001685 | Biological Factors |