Hypophosphatasia
Conditions
Keywords
Hypophosphatasia, HPP, Bone Disease, Soft Bones, Low Alkaline Phosphatase, Genetic metabolic disorder, Alkaline phosphatase, Tissue-specific alkaline phosphatase (TNSALP), Rickets, Osteomalacia
Brief summary
This clinical trial was conducted to study hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study was to test the safety and efficacy of a study drug called asfotase alfa (human recombinant tissue non-specific alkaline phosphate fusion protein) to see what effects it has on patients 5 years of age or less with HPP.
Detailed description
Asfotase alfa was formerly referred to as ENB-0040 Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.
Interventions
DRUGasfotase alfa
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Minutes to 5 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all of the following criteria for enrollment in this study: 1. Parent or legal guardian(s) must provide written informed consent prior to any study procedures being performed and must be willing to comply with all study-required procedures. Where appropriate and required by local regulations, patient assent should also be provided prior to any study procedures being performed. 2. Documented diagnosis of HPP as indicated by: 1. Total serum alkaline phosphatase (ALP) below the lower limit of normal for age NOTE: Historical values for ALP may be used to determine patient eligibility. 2. Plasma pyridoxal-5'-phosphate (PLP) above the upper limit of normal (unless patient is receiving pyridoxine for seizures) NOTE: Historical values for PLP may be used to determine patient eligibility. 3. Radiographic evidence of HPP at screening, characterized by: * Flared and frayed metaphyses, and * Severe, generalized osteopenia, and * Widened growth plates, and * Areas of radiolucency or sclerosis 4. Two or more of the following HPP-related findings: * History or presence of: i) Nontraumatic post-natal fracture or ii) Delayed fracture healing * Nephrocalcinosis or history of elevated serum calcium * Functional craniosynostosis * Respiratory compromise or rachitic chest deformity * Vitamin B6-responsive seizures * Failure to thrive 3. Onset of symptoms prior to 6 months of age 4. Chronological age or adjusted age for premature infants born ≤ 37 weeks gestation of ≤ 5 years 5. Otherwise medically stable in the opinion of the Investigator and/or Sponsor
Exclusion criteria
Patients will be excluded from enrollment in this study if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) | From Baseline to Week 24 | The effect of asfotase alfa treatment on skeletal manifestations of HPP (i.e., change in rickets severity) was measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale. Skeletal radiographs obtained at Week 24 were compared with skeletal radiographs obtained before initiation of treatment. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets). |
| Safety and Tolerability of Repeated Subcutaneous (SC) Injections of Asfotase Alfa | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients was assessed by the number of patients with 1 or more treatment-emergent adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Asfotase Alfa Treatment on Respiratory Function | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | Effect of asfotase alfa treatment on respiratory function as measured by the shift in proportion of patients requiring respiratory support at their last assessment compared with Baseline. |
| Effect of Asfotase Alfa Treatment on Physical Growth - Length/Height Z-scores Change From Baseline to Last Obtained Value | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | Effect of asfotase alfa treatment on physical growth as measured by change from Baseline to last assessment for each patient in length/height Z-scores |
| Effect of Asfotase Alfa Treatment on Physical Growth - Weight Z-scores Change From Baseline to Last Obtained Value | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | Effect of asfotase alfa treatment on physical growth as measured by change from Baseline to last assessment for each patient in weight Z-scores |
| Effect of Asfotase Alfa on Biomarkers - Plasma Inorganic Pyrophosphate (PPi) Change From Baseline to Last Obtained Value | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | Effect of asfotase alfa on PPi as measured by change from Baseline to last assessment for each patient |
| Effect of Asfotase Alfa on Biomarkers - Plasma Pyridoxal-5' Phosphate (PLP) Change From Baseline to Last Obtained Value | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | Effect of asfotase alfa on PLP as measured by change from Baseline to last assessment for each patient |
| Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) | Up to 72 Months or regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | The effect of asfotase alfa treatment on skeletal manifestations of HPP (i.e., change in rickets severity) was measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale. Skeletal radiographs obtained at the patient's last assessment were compared with skeletal radiographs obtained before initiation of treatment. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets). |
| Effect of Asfotase Alfa Treatment on Tooth Loss | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | Effect of asfotase alfa treatment on tooth loss assessed by the proportion of patients who experienced tooth loss during the study |
| Pharmacokinetic (PK) Properties of Asfotase Alfa (Tlast) | PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose | The PK properties (tlast) of asfotase alfa |
| Pharmacokinetic (PK) Properties of Asfotase Alfa (Tmax) | PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose | The PK properties (tmax) of asfotase alfa |
| Pharmacokinetic (PK) Properties of Asfotase Alfa (Cmax) | PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose | The PK properties (Cmax) of asfotase alfa |
| Pharmacokinetic (PK) Properties of Asfotase Alfa (AUCt) | PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose | The PK properties (AUCt) of asfotase alfa |
| Effect of Asfotase Alfa on Serum Parathyroid Hormone (PTH) - Change From Baseline to Last Obtained Value | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | Effect of asfotase alfa on serum PTH as measured by change from Baseline to last assessment for each patient |
| Effect of Asfotase Alfa Treatment on Ventilator-free Survival (Week 312) | Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years). | For patients who were not on respiratory support at the time of enrollment, the Kaplan-Meier estimate of ventilator-free survival at the end of the study |
Countries
Australia, Canada, France, Germany, Italy, Japan, Russia, Saudi Arabia, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The main criteria for inclusion in the study were male and female patients less than or equal to 5 years of age with a documented diagnosis of infantile onset hypophosphatasia (HPP) who were otherwise medically stable. Patients must have had onset of HPP signs/symptoms prior to 6 months of age.
Participants by arm
| Arm | Count |
|---|---|
| Asfotase Alfa A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week) | 69 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 6 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Asfotase Alfa |
|---|---|
| Age, Continuous | 113.42 weeks STANDARD_DEVIATION 108.912 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Race/Ethnicity, Customized Unknown | 5 Participants |
| Race/Ethnicity, Customized White | 54 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 9 / 69 |
| other Total, other adverse events | 68 / 69 |
| serious Total, serious adverse events | 50 / 69 |
Outcome results
Primary
Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP)
The effect of asfotase alfa treatment on skeletal manifestations of HPP (i.e., change in rickets severity) was measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale. Skeletal radiographs obtained at Week 24 were compared with skeletal radiographs obtained before initiation of treatment. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets).
Time frame: From Baseline to Week 24
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) | 2.00 scores on a scale |
Primary
Safety and Tolerability of Repeated Subcutaneous (SC) Injections of Asfotase Alfa
Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients was assessed by the number of patients with 1 or more treatment-emergent adverse event.
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Asfotase Alfa | Safety and Tolerability of Repeated Subcutaneous (SC) Injections of Asfotase Alfa | 69 Participants |
Secondary
Effect of Asfotase Alfa on Biomarkers - Plasma Inorganic Pyrophosphate (PPi) Change From Baseline to Last Obtained Value
Effect of asfotase alfa on PPi as measured by change from Baseline to last assessment for each patient
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa on Biomarkers - Plasma Inorganic Pyrophosphate (PPi) Change From Baseline to Last Obtained Value | -2.460 uM |
Secondary
Effect of Asfotase Alfa on Biomarkers - Plasma Pyridoxal-5' Phosphate (PLP) Change From Baseline to Last Obtained Value
Effect of asfotase alfa on PLP as measured by change from Baseline to last assessment for each patient
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa on Biomarkers - Plasma Pyridoxal-5' Phosphate (PLP) Change From Baseline to Last Obtained Value | -395.40 ng/mL |
Secondary
Effect of Asfotase Alfa on Serum Parathyroid Hormone (PTH) - Change From Baseline to Last Obtained Value
Effect of asfotase alfa on serum PTH as measured by change from Baseline to last assessment for each patient
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa on Serum Parathyroid Hormone (PTH) - Change From Baseline to Last Obtained Value | 0.70 pmol/L |
Secondary
Effect of Asfotase Alfa Treatment on Physical Growth - Length/Height Z-scores Change From Baseline to Last Obtained Value
Effect of asfotase alfa treatment on physical growth as measured by change from Baseline to last assessment for each patient in length/height Z-scores
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Physical Growth - Length/Height Z-scores Change From Baseline to Last Obtained Value | 0.5 Z-score |
Secondary
Effect of Asfotase Alfa Treatment on Physical Growth - Weight Z-scores Change From Baseline to Last Obtained Value
Effect of asfotase alfa treatment on physical growth as measured by change from Baseline to last assessment for each patient in weight Z-scores
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Physical Growth - Weight Z-scores Change From Baseline to Last Obtained Value | 1.0 Z-score |
Secondary
Effect of Asfotase Alfa Treatment on Respiratory Function
Effect of asfotase alfa treatment on respiratory function as measured by the shift in proportion of patients requiring respiratory support at their last assessment compared with Baseline.
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Respiratory Function | Other | 1 Participants |
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Respiratory Function | Biphasic positive airway pressure | 0 Participants |
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Respiratory Function | Mechanical ventilation | 13 Participants |
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Respiratory Function | No respiratory support | 45 Participants |
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Respiratory Function | Continuous positive airway pressure | 4 Participants |
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Respiratory Function | Supplemental oxygen | 6 Participants |
| Asfotase Alfa - Without Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Continuous positive airway pressure | 1 Participants |
| Asfotase Alfa - Without Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Mechanical ventilation | 0 Participants |
| Asfotase Alfa - Without Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Supplemental oxygen | 1 Participants |
| Asfotase Alfa - Without Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Other | 0 Participants |
| Asfotase Alfa - Without Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | No respiratory support | 43 Participants |
| Asfotase Alfa - Without Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Biphasic positive airway pressure | 0 Participants |
| Asfotase Alfa - With Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Biphasic positive airway pressure | 0 Participants |
| Asfotase Alfa - With Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | No respiratory support | 11 Participants |
| Asfotase Alfa - With Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Supplemental oxygen | 2 Participants |
| Asfotase Alfa - With Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Other | 0 Participants |
| Asfotase Alfa - With Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Continuous positive airway pressure | 2 Participants |
| Asfotase Alfa - With Respiratory Support at Baseline | Effect of Asfotase Alfa Treatment on Respiratory Function | Mechanical ventilation | 9 Participants |
Secondary
Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP)
The effect of asfotase alfa treatment on skeletal manifestations of HPP (i.e., change in rickets severity) was measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale. Skeletal radiographs obtained at the patient's last assessment were compared with skeletal radiographs obtained before initiation of treatment. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets).
Time frame: Up to 72 Months or regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP) | 2.33 scores on a scale |
Secondary
Effect of Asfotase Alfa Treatment on Tooth Loss
Effect of asfotase alfa treatment on tooth loss assessed by the proportion of patients who experienced tooth loss during the study
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Tooth Loss | 42 Participants |
Secondary
Effect of Asfotase Alfa Treatment on Ventilator-free Survival (Week 312)
For patients who were not on respiratory support at the time of enrollment, the Kaplan-Meier estimate of ventilator-free survival at the end of the study
Time frame: Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Population: Patients on respiratory support at Baseline were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asfotase Alfa | Effect of Asfotase Alfa Treatment on Ventilator-free Survival (Week 312) | 0.81 Probability |
Secondary
Pharmacokinetic (PK) Properties of Asfotase Alfa (AUCt)
The PK properties (AUCt) of asfotase alfa
Time frame: PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Population: 14 out of the total 69 subjects had provided sufficient concentration-time data for PK analysis and estimating the PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asfotase Alfa | Pharmacokinetic (PK) Properties of Asfotase Alfa (AUCt) | 66042 h*ng/mL | Standard Deviation 25758 |
Secondary
Pharmacokinetic (PK) Properties of Asfotase Alfa (Cmax)
The PK properties (Cmax) of asfotase alfa
Time frame: PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Population: 14 out of the total 69 subjects had provided sufficient concentration-time data for PK analysis and estimating the PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asfotase Alfa | Pharmacokinetic (PK) Properties of Asfotase Alfa (Cmax) | 1794 ng/mL | Standard Deviation 690 |
Secondary
Pharmacokinetic (PK) Properties of Asfotase Alfa (Tlast)
The PK properties (tlast) of asfotase alfa
Time frame: PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Population: \[14 out of the total 69 subjects had provided sufficient concentration-time data for PK analysis and estimating the PK parameters\]
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asfotase Alfa | Pharmacokinetic (PK) Properties of Asfotase Alfa (Tlast) | 48.1 hours | Standard Deviation 0.1 |
Secondary
Pharmacokinetic (PK) Properties of Asfotase Alfa (Tmax)
The PK properties (tmax) of asfotase alfa
Time frame: PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Population: 14 out of the total 69 subjects had provided sufficient concentration-time data for PK analysis and estimating the PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asfotase Alfa | Pharmacokinetic (PK) Properties of Asfotase Alfa (Tmax) | 14.9 hours | Standard Deviation 10.4 |