Hemophilia A
Conditions
Brief summary
The purpose of this study is to determine the pharmacokinetics and safety of Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) reconstituted in 2 mL sterile water for injection (SWFI) and compare with those of rAHF-PFM reconstituted in 5 mL of SWFI.
Interventions
BIOLOGICALAntihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
Subjects are randomized to receive an infusion of rAHF-PFM reconstituted in 2 mL sterile water for infusion (SWFI) followed (after a wash-out period) by rAHF-PFM reconstituted in 5 mL SWFI or in 5 mL then 2 mL SWFI(cross-over design). Each subject will receive 2 infusions.
Sponsors
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The subject or subject's legally authorized representative has provided written informed consent * The subject has severe hemophilia A as defined by a baseline FVIII activity \<= 1% of normal; tested at screening * The adolescent/adult subject has a documented history of at least 150 exposure days to FVIII concentrates (either plasma-derived or recombinant), and the pediatric subject has at least 50 exposure days * The subject is \>= 12 to \<= 65 years of age for the complete pharmacokinetic assessment and \>= 2 to \< 12 years for the incremental recovery assessment The subject has a Karnofsky performance score \> 60 * The subject is human immunodeficiency virus negative (HIV-) or HIV+ with stable CD4 count \>= 200 cells/mm³ (CD4 count determined at screening, if necessary)
Exclusion criteria
* The subject has a known hypersensitivity to mouse or hamster proteins or to FVIII concentrates * The subject has a history of FVIII inhibitors with titer \>= 0. 5 BU (Bethesda Assay) or \>= 0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to screening * The subject has a detectable FVIII inhibitor at screening, \>= 0.4 BU (Nijmegen modification of the Bethesda Assay), in the central laboratory * The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) \> 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices * The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (e.g. qualitative platelet defect or Von Willebrand Disease) * The subject has received another investigational product within 30 days of enrollment * The subject's clinical condition may require major or moderate surgery (estimated blood loss \> 500 mL) during the period of participation in the study * Subjects with clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance * The subject is a female of childbearing potential with a positive pregnancy test at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve | Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion | Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted in Vivo Incremental Recovery | Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion | Increase in factor VIII concentration from pre- to post-infusion |
| Terminal Half-life | Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion | Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%. |
| Weight-Adjusted Clearance | Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion | Computed as the weight-adjusted dose divided by total AUC |
| Mean Residence Time | Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion | Computed as total area under the moment curve divided by the total AUC. Total area under the first moment curve (AUMC) estimated by linear trapezoidal methods |
| Total Area Under the Curve | Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion | Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model |
| Maximum Plasma Concentration | Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion | Maximal factor VIII concentration post-infusion |
| Number and Severity of Infusion Site Reactions | Within 5 minutes pre-infusion up to 24 hours post-infusion | Infusion-related local reactions (including pain, tenderness, erythema, induration, and bruising) and severity were evaluated according to an FDA-defined grading scale (FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials; 2007). |
| Infusion Site Pain | Within 5 minutes post-infusion up to 24 hours post-infusion | Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain). |
| Volume of Distribution at Steady State | Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion | Computed as weight-adjusted clearance \* mean residence time |
Countries
United States
Participant flow
Recruitment details
Enrollment was conducted in the United States at 11 sites. Two cohorts were recruited (adolescent/adults aged ≥12 to ≤65 years and pediatrics aged ≥2 to \<12 years).
Pre-assignment details
Subjects meeting inclusion criteria were randomly assigned to receive a single sequence of 2 pharmacokinetic (PK) infusions of rAHF-PFM: reconstituted in 2mL then 5mL sterile water for injection (SWFI) or vice versa. Before each PK evaluation ≥3 day washout and negative factor VIII inhibitor titer was required. Ten subjects were screen failures
Participants by arm
| Arm | Count |
|---|---|
| Treated Participants Participants who received at least 1 infusion | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 1st Pharmacokinetic Evaluation | Lost to Follow-up | 0 | 1 | 0 | 0 |
| 2nd Pharmacokinetic Evaluation | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Treated Participants |
|---|---|
| Age, Continuous Adolescents/Adults | 26 years STANDARD_DEVIATION 10 |
| Age, Continuous Pediatrics | 6 years STANDARD_DEVIATION 3 |
| Age, Customized ≥12 to <16 years (Number Adolescents) | 3 Participants |
| Age, Customized ≥16 to 65 years (Number Adults) | 24 Participants |
| Age, Customized ≥2 to <12 years (Number Pediatrics) | 15 Participants |
| Region of Enrollment United States | 42 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 27 | 10 / 15 |
| serious Total, serious adverse events | 0 / 27 | 1 / 15 |
Outcome results
Primary
Area Under the Curve
Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Population: Number of complete crossover participants (per protocol) who received the assigned sequence of 2 infusions: reconstituted in 2mL then 5mL SWFI or in 5mL then 2mL SWFI.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Area Under the Curve | 1257.20 IU*h/dL | Standard Deviation 380.6 |
| Adolescents/Adults - 5 mL | Area Under the Curve | 1297.42 IU*h/dL | Standard Deviation 487.57 |
90% CI: [-0.117, 0.012]
Secondary
Adjusted in Vivo Incremental Recovery
Increase in factor VIII concentration from pre- to post-infusion
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion
Population: Intent to Treat
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Adjusted in Vivo Incremental Recovery | 1.87 IU/dL:IU/kg | Standard Deviation 0.34 |
| Adolescents/Adults - 5 mL | Adjusted in Vivo Incremental Recovery | 1.88 IU/dL:IU/kg | Standard Deviation 0.4 |
| Pediatrics - 2 mL | Adjusted in Vivo Incremental Recovery | 1.33 IU/dL:IU/kg | Standard Deviation 0.36 |
| Pediatrics - 5 mL | Adjusted in Vivo Incremental Recovery | 1.66 IU/dL:IU/kg | Standard Deviation 0.25 |
Secondary
Infusion Site Pain
Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain).
Time frame: Within 5 minutes post-infusion up to 24 hours post-infusion
Population: Participants who received at least 1 infusion
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Infusion Site Pain | 6 hours ± 30 minutes after infusion | 0 Scores on a scale |
| Adolescents/Adults - 2 mL | Infusion Site Pain | Within 5 minutes (immediately) after infusion | 0 Scores on a scale |
| Adolescents/Adults - 2 mL | Infusion Site Pain | 24 hours after infusion | 0 Scores on a scale |
| Adolescents/Adults - 2 mL | Infusion Site Pain | 60 ± 5 minutes after infusion | 0 Scores on a scale |
| Adolescents/Adults - 5 mL | Infusion Site Pain | Within 5 minutes (immediately) after infusion | 0 Scores on a scale |
| Adolescents/Adults - 5 mL | Infusion Site Pain | 24 hours after infusion | 0 Scores on a scale |
| Adolescents/Adults - 5 mL | Infusion Site Pain | 60 ± 5 minutes after infusion | 0 Scores on a scale |
| Adolescents/Adults - 5 mL | Infusion Site Pain | 6 hours ± 30 minutes after infusion | 0 Scores on a scale |
| Pediatrics - 2 mL | Infusion Site Pain | 24 hours after infusion | 0 Scores on a scale |
| Pediatrics - 2 mL | Infusion Site Pain | Within 5 minutes (immediately) after infusion | 8 Scores on a scale |
| Pediatrics - 2 mL | Infusion Site Pain | 6 hours ± 30 minutes after infusion | 0 Scores on a scale |
| Pediatrics - 2 mL | Infusion Site Pain | 60 ± 5 minutes after infusion | 2.5 Scores on a scale |
| Pediatrics - 5 mL | Infusion Site Pain | 24 hours after infusion | 0 Scores on a scale |
| Pediatrics - 5 mL | Infusion Site Pain | Within 5 minutes (immediately) after infusion | 4 Scores on a scale |
| Pediatrics - 5 mL | Infusion Site Pain | 60 ± 5 minutes after infusion | 1 Scores on a scale |
| Pediatrics - 5 mL | Infusion Site Pain | 6 hours ± 30 minutes after infusion | 0 Scores on a scale |
Secondary
Maximum Plasma Concentration
Maximal factor VIII concentration post-infusion
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Population: Per Protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Maximum Plasma Concentration | 102.77 IU/dL | Standard Deviation 19.35 |
| Adolescents/Adults - 5 mL | Maximum Plasma Concentration | 106.46 IU/dL | Standard Deviation 17.95 |
Secondary
Mean Residence Time
Computed as total area under the moment curve divided by the total AUC. Total area under the first moment curve (AUMC) estimated by linear trapezoidal methods
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Mean Residence Time | 14.79 hours (h) | Standard Deviation 5.24 |
| Adolescents/Adults - 5 mL | Mean Residence Time | 14.34 hours (h) | Standard Deviation 4.27 |
Secondary
Number and Severity of Infusion Site Reactions
Infusion-related local reactions (including pain, tenderness, erythema, induration, and bruising) and severity were evaluated according to an FDA-defined grading scale (FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials; 2007).
Time frame: Within 5 minutes pre-infusion up to 24 hours post-infusion
Population: Participants who received at least 1 infusion
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Induration- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Erythema- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Pain- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Induration- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Induration- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Pain- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Induration- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Bruising- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Tenderness- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Bruising- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Tenderness- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Pain- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Bruising- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Tenderness- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Tenderness- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Pain- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Bruising- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Erythema- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Erythema- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 2 mL | Number and Severity of Infusion Site Reactions | Erythema- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Induration- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Erythema- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Bruising- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Induration- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Tenderness- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Erythema- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Pain- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Erythema- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Erythema- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Induration- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Tenderness- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Induration- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Pain- Moderate (Grade 2) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Pain- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Bruising- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Bruising- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Pain- Severe (Grade 3) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Tenderness- Mild (Grade 1) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Tenderness- Potentially Life Threatening (Grade 4) | 0 Participants |
| Adolescents/Adults - 5 mL | Number and Severity of Infusion Site Reactions | Bruising- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Induration- Mild (Grade 1) | 1 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Pain- Mild (Grade 1) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Pain- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Pain- Severe (Grade 3) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Pain- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Tenderness- Mild (Grade 1) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Tenderness- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Tenderness- Severe (Grade 3) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Tenderness- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Erythema- Mild (Grade 1) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Erythema- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Erythema- Severe (Grade 3) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Erythema- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Induration- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Induration- Severe (Grade 3) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Induration- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Bruising- Mild (Grade 1) | 1 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Bruising- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Bruising- Severe (Grade 3) | 0 Participants |
| Pediatrics - 2 mL | Number and Severity of Infusion Site Reactions | Bruising- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Erythema- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Erythema- Mild (Grade 1) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Bruising- Severe (Grade 3) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Induration- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Tenderness- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Tenderness- Severe (Grade 3) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Pain- Mild (Grade 1) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Bruising- Mild (Grade 1) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Tenderness- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Tenderness- Mild (Grade 1) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Pain- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Bruising- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Pain- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Induration- Mild (Grade 1) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Pain- Severe (Grade 3) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Induration- Moderate (Grade 2) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Erythema- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Erythema- Severe (Grade 3) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Bruising- Potentially Life Threatening (Grade 4) | 0 Participants |
| Pediatrics - 5 mL | Number and Severity of Infusion Site Reactions | Induration- Severe (Grade 3) | 0 Participants |
Secondary
Terminal Half-life
Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Terminal Half-life | 12.54 hours | Standard Deviation 3.8 |
| Adolescents/Adults - 5 mL | Terminal Half-life | 12.50 hours | Standard Deviation 2.89 |
Secondary
Total Area Under the Curve
Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Population: Number of complete crossover participants (intent to treat) who received the assigned sequence of 2 infusions: reconstituted in 2mL then 5mL SWFI or in 5mL then 2mL SWFI.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Total Area Under the Curve | 1357.60 IU*h/dL | Standard Deviation 436.24 |
| Adolescents/Adults - 5 mL | Total Area Under the Curve | 1368.12 IU*h/dL | Standard Deviation 553.21 |
90% CI: [-0.076, 0.043]
Secondary
Volume of Distribution at Steady State
Computed as weight-adjusted clearance \* mean residence time
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Volume of Distribution at Steady State | 0.54 dL/kg | Standard Deviation 0.13 |
| Adolescents/Adults - 5 mL | Volume of Distribution at Steady State | 0.51 dL/kg | Standard Deviation 0.13 |
Secondary
Weight-Adjusted Clearance
Computed as the weight-adjusted dose divided by total AUC
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Adolescents/Adults - 2 mL | Weight-Adjusted Clearance | 3.85 mL/(kg*h) | Standard Deviation 0.95 |
| Adolescents/Adults - 5 mL | Weight-Adjusted Clearance | 3.81 mL/(kg*h) | Standard Deviation 1.2 |