Trial Outcomes & Findings for Pharmacokinetic and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP) (NCT NCT02797821)

Last Updated: 2019-09-17

Results Overview

Plasma PPi concentrations were determined using a specific enzyme-catalyzed reaction with a radiolabelled marker in a 3-step process. Baseline plasma PPi values were calculated by averaging pre-dose values from samples collected during the Run-in Period at -168, -156, -24, -12, and 0 hours before Baseline. Week 9 plasma PPi values were calculated using blood samples collected before administration of the 3rd dose. The analysis was a restricted maximum likelihood (REML)-based repeated measures mixed model with treatment, visit, sex, Baseline PPi, Baseline weight group (≥ median versus \< median), and study drug lot assignment as factors, and an unstructured covariance structure for within-participant correlation. Per inclusion criteria, participants had to have had a Screening PPi concentration of ≥3.9 micromolar (μM). Three participants (1 in each group) had Screening PPi concentrations of ≥3.9 μM, but Baseline PPi values ranged between 3.5 to 3.8 μM.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

Baseline to Week 9

Results posted on

2019-09-17

Participant Flow

Participant milestones

Participant milestones
Measure	Asfotase Alfa 0.5 mg/kg Dose Participants received 0.5 milligrams (mg) per kilogram (kg) of asfotase alfa administered subcutaneously (SC) 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 2.0 mg/kg Dose Participants received 2.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 3.0 mg/kg Dose Participants received 3.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.
Overall Study STARTED	8	10	9
Overall Study Received at Least 1 Dose of Study Drug	8	10	9
Overall Study COMPLETED	8	10	9
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetic and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Asfotase Alfa 0.5 mg/kg Dose n=8 Participants Participants received 0.5 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 2.0 mg/kg Dose n=10 Participants Participants received 2.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 3.0 mg/kg Dose n=9 Participants Participants received 3.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Total n=27 Participants Total of all reporting groups
Age, Continuous	41.5 years STANDARD_DEVIATION 17.90 • n=5 Participants	42.7 years STANDARD_DEVIATION 16.77 • n=7 Participants	50 years STANDARD_DEVIATION 17.01 • n=5 Participants	44.8 years STANDARD_DEVIATION 16.94 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	27 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	26 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Baseline Inorganic Pyrophosphate (PPi)	5.4 μM (micromolar) STANDARD_DEVIATION 1.64 • n=5 Participants	5.3 μM (micromolar) STANDARD_DEVIATION 1.22 • n=7 Participants	5 μM (micromolar) STANDARD_DEVIATION 0.86 • n=5 Participants	5.2 μM (micromolar) STANDARD_DEVIATION 1.23 • n=4 Participants
Baseline Pyridoxal 5'-Phosphate (PLP)	309.5 nanogram (ng)/milliliter (mL) STANDARD_DEVIATION 349.16 • n=5 Participants	382.1 nanogram (ng)/milliliter (mL) STANDARD_DEVIATION 385.89 • n=7 Participants	229.5 nanogram (ng)/milliliter (mL) STANDARD_DEVIATION 321.43 • n=5 Participants	309.7 nanogram (ng)/milliliter (mL) STANDARD_DEVIATION 346.99 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 9

Population: FAS: randomized participants who received ≥1 dose of study drug and had ≥1 pretreatment and ≥1 on-treatment PPi result.

Outcome measures

Outcome measures
Measure	Asfotase Alfa 0.5 mg/kg Dose n=8 Participants Participants received 0.5 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 2.0 mg/kg Dose n=10 Participants Participants received 2.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 3.0 mg/kg Dose n=8 Participants Participants received 3.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.
Change In Plasma PPi From Baseline To Pre-3rd Dose At Week 9	-2.604 μM Standard Error 0.2399	-3.797 μM Standard Error 0.1949	-4.484 μM Standard Error 0.2120

SECONDARY outcome

Timeframe: Baseline to Week 9

Population: FAS: randomized participants who received ≥1 dose of study drug and had ≥1 pretreatment and ≥1 on-treatment PPi result.

Plasma PLP was quantified using liquid chromatography/mass spectrometry. Baseline plasma PLP values were calculated by averaging the pre-dose PLP values from blood samples collected during the Run-in Period at -168, -156, -24, -12, and 0 hours before Baseline. Week 9 PLP values were calculated using blood samples collected before the administration of the 3rd dose. The analysis was a REML-based repeated measures mixed model with treatment, visit, sex, Baseline PPi, Baseline weight group (≥ median versus \< median) and study drug lot assignment as factors, and an unstructured covariance structure for within-participant correlation.

Outcome measures

Outcome measures
Measure	Asfotase Alfa 0.5 mg/kg Dose n=8 Participants Participants received 0.5 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 2.0 mg/kg Dose n=10 Participants Participants received 2.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 3.0 mg/kg Dose n=9 Participants Participants received 3.0 mg/kg of asfotase alfa administered SC 3 times a week from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.
Change In Plasma PLP From Baseline To Pre-3rd Dose At Week 9	-303.955 ng/mL Standard Error 9.4075	-333.447 ng/mL Standard Error 8.1486	-338.002 ng/mL Standard Error 85145

Adverse Events

Asfotase Alfa 0.5 mg/kg Dose

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Asfotase Alfa 2.0 mg/kg Dose

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Asfotase Alfa 3.0 mg/kg Dose

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Alexion Pharmaceuticals

Phone: 475-230-2596

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Asfotase Alfa 0.5 mg/kg Dose n=8 participants at risk Participants received 0.5 mg/kg of asfotase alfa administered SC 3 times a week (1 dose each on Mondays, Wednesdays, and Fridays) from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 2.0 mg/kg Dose n=10 participants at risk Participants received 2.0 mg/kg of asfotase alfa administered SC 3 times a week (1 dose each on Mondays, Wednesdays, and Fridays) from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.	Asfotase Alfa 3.0 mg/kg Dose n=9 participants at risk Participants received 3.0 mg/kg of asfotase alfa administered SC 3 times a week (1 dose each on Mondays, Wednesdays, and Fridays) from Weeks 3 through 9 following the initial single dose on Day 1 in Week 1.
General disorders Fatigue	37.5% 3/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	40.0% 4/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	33.3% 3/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Injection site erythema	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	30.0% 3/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	44.4% 4/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Injection site reaction	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	30.0% 3/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	44.4% 4/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Injection site pain	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	33.3% 3/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Pain	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	20.0% 2/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Feeling hot	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	22.2% 2/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Influenza like illness	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Injection site bruising	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Injection site discomfort	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Injection site haematoma	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Peripheral swelling	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
General disorders Pyrexia	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Musculoskeletal and connective tissue disorders Pain in extremity	50.0% 4/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	50.0% 5/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	44.4% 4/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Musculoskeletal and connective tissue disorders Arthralgia	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	40.0% 4/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	55.6% 5/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Musculoskeletal and connective tissue disorders Back pain	50.0% 4/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	22.2% 2/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Musculoskeletal and connective tissue disorders Bone pain	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	30.0% 3/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	22.2% 2/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	37.5% 3/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Musculoskeletal and connective tissue disorders Myalgia	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Nervous system disorders Headache	37.5% 3/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	30.0% 3/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	55.6% 5/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Nervous system disorders Paraesthesia	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	44.4% 4/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Nervous system disorders Disturbance in attention	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Nervous system disorders Head discomfort	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Nervous system disorders Hypersomnia	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Infections and infestations Upper respiratory tract infection	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	30.0% 3/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Infections and infestations Viral upper respiratory tract infection	50.0% 4/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Gastrointestinal disorders Nausea	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	22.2% 2/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Gastrointestinal disorders Abdominal pain	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Gastrointestinal disorders Flatulence	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	20.0% 2/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Injury, poisoning and procedural complications Contusion	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	33.3% 3/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Injury, poisoning and procedural complications Laceration	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Psychiatric disorders Anxiety	0.00% 0/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	33.3% 3/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Psychiatric disorders Insomnia	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	22.2% 2/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Psychiatric disorders Restlessness	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Skin and subcutaneous tissue disorders Erythema	25.0% 2/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	30.0% 3/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	11.1% 1/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.
Skin and subcutaneous tissue disorders Pruritus	12.5% 1/8 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	10.0% 1/10 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.	0.00% 0/9 • Adverse events (AE) were monitored continuously throughout the study, from the run-in period through the safety follow-up call, which occurred 90 days after the last dose of study drug. Results for AEs occurred in \>5% of the overall Safety population. An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device, which did not necessarily have a causal relationship with the asfotase alfa.