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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003685-88 | EudraCT Number |
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An open-label, single dose pharmacokinetic study of Xyntha (Moroctocog Alfa (AF-CC), Recombinant Factor VIII) in male Chinese subjects with hemophilia A
The purpose of this study is to obtain pharmacokinetic profiles of FVIII:C after Xyntha administration in Chinese patients with severe hemophilia A, which is in support of the continued registration of Xyntha in China
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous infusion of Xyntha | Experimental | observation arm |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous infusions of Xyntha | Drug | A single dose 50IU/kg dose of Xyntha administered by intravenous infusion within 10 minutes on Day 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma FVIII Activity (Cmax) | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose | |
| Area Under the Plasma FVIII Activity-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast) | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose | |
| Area Under the Plasma FVIII Activity-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose | |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose | |
| Clearance (CL) | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
| Volume of Distribution at Steady-State (Vss) | Volume of distribution is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the volume of distribution at steady-state. | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
| Terminal Phase Rate Constant (Kel) | Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs. |
Inclusion Criteria:
Subjects must meet all of the following inclusion criteria to be eligible for enrollment in the study:
Exclusion Criteria:
Subjects with any of the following characteristics/conditions will not be included in the study:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phase I Unit, Clinical Pharmacology Research Center, Peking Union Medical College Hospital | Beijing | 100032 | China | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28601434 | Derived | Liu H, Wu R, Hu P, Sun F, Xu L, Liang Y, Nepal S, Qu PR, Huard F, Korth-Bradley JM. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A. Clin Ther. 2017 Jul;39(7):1313-1319. doi: 10.1016/j.clinthera.2017.05.344. Epub 2017 Jun 7. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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This study recruited Chinese male participants that were age 6 years or older with severe hemophilia A (factor VIII [FVIII] activity <1%) previously treated with >150 exposure days to any FVIII-containing product.
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| ID | Title | Description |
|---|---|---|
| FG000 | Xyntha 50 IU/kg | Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The baseline analysis population included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Xyntha 50 IU/kg | Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | Maximum Plasma FVIII Activity (Cmax) | The pharmacokinetic (PK) parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | IU/milliliter (mL) | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
Baseline up to Day 28
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Xyntha 50 IU/kg | Participants were administered a single dose of recombinant antihemophilic factor (Xyntha) at 50 international units per kilogram (IU/kg) infused intravenously over 10 minutes. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Factor VIII inhibition | Blood and lymphatic system disorders | MedDRA version 18.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 18.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
| Terminal Elimination Half-Life (t1/2) | Terminal half-life is the time measured for the plasma concentration to decrease by one half. | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
| Mean Residence Time (MRT) | MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method. | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
| Incremental Recovery (INCREC) | Incremental recovery is the increase in circulating FVIII activity for every IU of Xyntha administered per kilogram of body weight. | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
| Baseline up to Day 28 |
| Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern | The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, RBC morphology, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (urine drug screening, FVIII inhibitor assay, FVIII activity, prothrombin time [PT], activated partial thromboplastin time [APTT], anti-human immunodeficiency virus [HIV] 1, hepatitis C virus antibody [HCVAb], HAVAb, HBsAg, HBsAb, HBcAb). Only parameters which met abnormality criteria are reported. | Baseline up to Day 4 |
| Number of Participants With Potentially Clinically Significant Vital Signs Findings | Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <50 beats per minute (bpm), >=30 bpm increase from baseline, or >25 bpm decrease from baseline; systolic blood pressure (SBP) <90 milliliters of mercury (mmHg), >=30 mmHg increase from baseline, or >=30 mmHg decrease from baseline; diastolic blood pressure (DBP) <50 mmHg, >=20 mmHg increase from baseline, or >=20 mmHg decrease from baseline. | Baseline up to Day 4 |
| Number of Participants With Positive FVIII Inhibitor Activity at Day 4 | As with all FVIII products, participants using Xyntha were monitored for the development of FVIII inhibitors. Values >= 0.6 Bethesda Unit (BU) per mL were considered positive results. | Day 4 |
| Hematology Department,Beijing Children's Hospital, Capital Medical University |
| Beijing |
| 100045 |
| China |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | Area Under the Plasma FVIII Activity-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast) | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | IU*hour/mL | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Primary | Area Under the Plasma FVIII Activity-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | IU*hour/mL | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Median | Full Range | hour | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Primary | Clearance (CL) | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/hour/kg | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Primary | Volume of Distribution at Steady-State (Vss) | Volume of distribution is the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the volume of distribution at steady-state. | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/kg | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Primary | Terminal Phase Rate Constant (Kel) | Terminal phase rate constant is the absolute value of the slope of a linear regression during the terminal phase of the natural--logarithm transformed concentration--time profile. | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | 1/hour | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Primary | Terminal Elimination Half-Life (t1/2) | Terminal half-life is the time measured for the plasma concentration to decrease by one half. | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Mean | Standard Deviation | hour | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Primary | Mean Residence Time (MRT) | MRT = AUMCinf / AUCinf, where AUMCinf is the area under the first moment curve from zero time to infinity calculated as AUMCinf = AUMCt + ((t x Ct) / kel) + (Ct / kel^2). AUMCt is the area under the first moment curve from zero time to time t calculated using the trapezoidal method. | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Primary | Incremental Recovery (INCREC) | Incremental recovery is the increase in circulating FVIII activity for every IU of Xyntha administered per kilogram of body weight. | The PK parameter analysis population is defined as all participants enrolled and treated who have at least 1 of the PK parameters of primary interest reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | IU/deciliter (dL) per IU/kg | Pre-dose and 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32, 48, and 72 hours post-dose |
|
|
|
| Other Pre-specified | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs. | The safety analysis population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline up to Day 28 |
|
|
|
| Other Pre-specified | Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern | The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, RBC morphology, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (urine drug screening, FVIII inhibitor assay, FVIII activity, prothrombin time [PT], activated partial thromboplastin time [APTT], anti-human immunodeficiency virus [HIV] 1, hepatitis C virus antibody [HCVAb], HAVAb, HBsAg, HBsAb, HBcAb). Only parameters which met abnormality criteria are reported. | The safety analysis population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline up to Day 4 |
|
|
|
| Other Pre-specified | Number of Participants With Potentially Clinically Significant Vital Signs Findings | Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine pulse rate <50 beats per minute (bpm), >=30 bpm increase from baseline, or >25 bpm decrease from baseline; systolic blood pressure (SBP) <90 milliliters of mercury (mmHg), >=30 mmHg increase from baseline, or >=30 mmHg decrease from baseline; diastolic blood pressure (DBP) <50 mmHg, >=20 mmHg increase from baseline, or >=20 mmHg decrease from baseline. | The safety analysis population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline up to Day 4 |
|
|
|
| Other Pre-specified | Number of Participants With Positive FVIII Inhibitor Activity at Day 4 | As with all FVIII products, participants using Xyntha were monitored for the development of FVIII inhibitors. Values >= 0.6 Bethesda Unit (BU) per mL were considered positive results. | The safety analysis population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | Day 4 |
|
|
|
| 2 |
| 13 |
| 2 |
| 13 |
| Headache | Nervous system disorders | MedDRA version 18.1 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Supine SBP >=30 mmHg Increase From Baseline |
|
| Supine DBP >=20 mmHg Increase From Baseline |
|
| Supine Pulse Rate >=30 bpm Increase From Baseline |
|
| Supine SBP >=30 mmHg Decrease From Baseline |
|
| Supine DBP >=20 mmHg Decrease From Baseline |
|
| Supine Pulse Rate >=25 bpm Increase From Baseline |
|