Trial Outcomes & Findings for Study of KRN23 in Adults With X-linked Hypophosphatemia (XLH) (NCT NCT02526160)

NCT ID: NCT02526160

Last Updated: 2024-06-18

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

134 participants

Primary outcome timeframe

Baseline through Week 24

Results posted on

2024-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).	Burosumab 1 mg/kg SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Double-Blind (Placebo-Controlled) Period STARTED	66	68
Double-Blind (Placebo-Controlled) Period COMPLETED	66	67
Double-Blind (Placebo-Controlled) Period NOT COMPLETED	0	1
Open-label Treatment Continuation Period STARTED	66	67
Open-label Treatment Continuation Period COMPLETED	63	63
Open-label Treatment Continuation Period NOT COMPLETED	3	4
Open-Label Treatment Extension Period I STARTED	63	63
Open-Label Treatment Extension Period I COMPLETED	60	59
Open-Label Treatment Extension Period I NOT COMPLETED	3	4
Open-Label Treatment Extension Period II STARTED	52	49
Open-Label Treatment Extension Period II COMPLETED	51	49
Open-Label Treatment Extension Period II NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II).	Burosumab 1 mg/kg SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II).
Double-Blind (Placebo-Controlled) Period Withdrawal by Subject	0	1
Open-label Treatment Continuation Period Withdrawal by Subject	0	1
Open-label Treatment Continuation Period Other, Not Specified	3	3
Open-Label Treatment Extension Period I Death	0	1
Open-Label Treatment Extension Period I Other, Not Specified	3	1
Open-Label Treatment Extension Period I Withdrawal by Subject	0	1
Open-Label Treatment Extension Period I Lost to Follow-up	0	1
Open-Label Treatment Extension Period II Other, Not Specified	1	0

Baseline Characteristics

participants with a baseline assessment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W	Total n=134 Participants Total of all reporting groups
Age, Continuous	38.65 years STANDARD_DEVIATION 12.756 • n=66 Participants	41.29 years STANDARD_DEVIATION 11.582 • n=68 Participants	39.99 years STANDARD_DEVIATION 12.201 • n=134 Participants
Sex: Female, Male Female	43 Participants n=66 Participants	44 Participants n=68 Participants	87 Participants n=134 Participants
Sex: Female, Male Male	23 Participants n=66 Participants	24 Participants n=68 Participants	47 Participants n=134 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=66 Participants	7 Participants n=68 Participants	12 Participants n=134 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants n=66 Participants	61 Participants n=68 Participants	122 Participants n=134 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=66 Participants	0 Participants n=68 Participants	0 Participants n=134 Participants
Race/Ethnicity, Customized Asian	9 Participants n=66 Participants	12 Participants n=68 Participants	21 Participants n=134 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=66 Participants	0 Participants n=68 Participants	3 Participants n=134 Participants
Race/Ethnicity, Customized White	53 Participants n=66 Participants	55 Participants n=68 Participants	108 Participants n=134 Participants
Race/Ethnicity, Customized Other, Not Specified	1 Participants n=66 Participants	1 Participants n=68 Participants	2 Participants n=134 Participants
Brief Pain Inventory (BPI) Worst Pain Score	6.54 score on a scale STANDARD_DEVIATION 1.433 • n=66 Participants	6.81 score on a scale STANDARD_DEVIATION 1.308 • n=68 Participants	6.68 score on a scale STANDARD_DEVIATION 1.372 • n=134 Participants
BPI Pain Severity Score	4.92 score on a scale STANDARD_DEVIATION 1.547 • n=66 Participants	5.18 score on a scale STANDARD_DEVIATION 1.531 • n=68 Participants	5.05 score on a scale STANDARD_DEVIATION 1.539 • n=134 Participants
BPI Pain Interference Score	4.76 score on a scale STANDARD_DEVIATION 2.174 • n=66 Participants	5.23 score on a scale STANDARD_DEVIATION 2.237 • n=68 Participants	5.00 score on a scale STANDARD_DEVIATION 2.210 • n=134 Participants
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score	61.36 score on a scale STANDARD_DEVIATION 20.770 • n=66 Participants	64.71 score on a scale STANDARD_DEVIATION 20.253 • n=68 Participants	63.06 score on a scale STANDARD_DEVIATION 20.500 • n=134 Participants
WOMAC Physical Function Score	43.89 score on a scale STANDARD_DEVIATION 19.938 • n=66 Participants	50.79 score on a scale STANDARD_DEVIATION 19.660 • n=68 Participants	47.40 score on a scale STANDARD_DEVIATION 20.024 • n=134 Participants
Brief Fatigue Inventory (BFI) Worst Fatigue Score	6.74 score on a scale STANDARD_DEVIATION 1.526 • n=66 Participants	6.94 score on a scale STANDARD_DEVIATION 1.657 • n=68 Participants	6.84 score on a scale STANDARD_DEVIATION 1.591 • n=134 Participants
BFI Global Fatigue Score	4.86 score on a scale STANDARD_DEVIATION 1.932 • n=66 Participants	5.37 score on a scale STANDARD_DEVIATION 2.044 • n=68 Participants	5.12 score on a scale STANDARD_DEVIATION 1.999 • n=134 Participants
Serum Procollagen Type 1 N- Propeptide (P1NP)	87.6 ng/mL STANDARD_DEVIATION 53.41 • n=66 Participants • participants with a baseline assessment	87.5 ng/mL STANDARD_DEVIATION 53.60 • n=67 Participants • participants with a baseline assessment	87.6 ng/mL STANDARD_DEVIATION 53.30 • n=133 Participants • participants with a baseline assessment
Serum Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx)	719.2 pg/mL STANDARD_DEVIATION 419.24 • n=66 Participants • participants with a baseline assessment	718.4 pg/mL STANDARD_DEVIATION 413.71 • n=67 Participants • participants with a baseline assessment	718.8 pg/mL STANDARD_DEVIATION 414.89 • n=133 Participants • participants with a baseline assessment
Serum Bone-Specific Alkaline Phosphatase (BALP)	24.6 μg/L STANDARD_DEVIATION 17.30 • n=66 Participants • participants with a baseline assessment	25.1 μg/L STANDARD_DEVIATION 21.55 • n=66 Participants • participants with a baseline assessment	24.9 μg/L STANDARD_DEVIATION 19.47 • n=132 Participants • participants with a baseline assessment
Serum Phosphorus	0.617 mmol/L STANDARD_DEVIATION 0.1001 • n=66 Participants	0.653 mmol/L STANDARD_DEVIATION 0.1072 • n=68 Participants	0.635 mmol/L STANDARD_DEVIATION 0.1050 • n=134 Participants
Serum 1, 25 (OH)2 D	33.5 pg/mL STANDARD_DEVIATION 15.61 • n=64 Participants • participants with a baseline assessment	32.4 pg/mL STANDARD_DEVIATION 12.96 • n=66 Participants • participants with a baseline assessment	33.0 pg/mL STANDARD_DEVIATION 14.28 • n=130 Participants • participants with a baseline assessment
24-Hour Urinary Phosphorus	0.81 g/24 hour STANDARD_DEVIATION 0.262 • n=65 Participants • participants with a baseline assessment	0.72 g/24 hour STANDARD_DEVIATION 0.241 • n=68 Participants • participants with a baseline assessment	0.77 g/24 hour STANDARD_DEVIATION 0.255 • n=133 Participants • participants with a baseline assessment
Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR)	1.598 mg/dL STANDARD_DEVIATION 0.3693 • n=64 Participants • participants with a baseline assessment	1.678 mg/dL STANDARD_DEVIATION 0.4004 • n=66 Participants • participants with a baseline assessment	1.639 mg/dL STANDARD_DEVIATION 0.3860 • n=130 Participants • participants with a baseline assessment
Tubular Reabsorption of Phosphate (TRP)	0.812 fraction of phosphate reabsorbed STANDARD_DEVIATION 0.0842 • n=64 Participants • participants with a baseline assessment	0.807 fraction of phosphate reabsorbed STANDARD_DEVIATION 0.0832 • n=67 Participants • participants with a baseline assessment	0.810 fraction of phosphate reabsorbed STANDARD_DEVIATION 0.0834 • n=131 Participants • participants with a baseline assessment

PRIMARY outcome

Timeframe: Baseline through Week 24

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24	7.6 percentage of participants Interval 3.3 to 16.5	92.6 percentage of participants Interval 83.9 to 96.8

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). From the generalized estimating equation (GEE) model, which includes the change from Baseline for the endpoint of interest as the dependent variable; region, visit, treatment, actual randomization stratification (not included for analysis of BPI Worst Pain), and visit by treatment as fixed factors; and Baseline value for the endpoint of interest as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline to Week 24 in Brief Pain Inventory (BPI) Question 3 (Q3; Worst Pain in Past 24 Hours) Score	-0.32 score on a scale Standard Error 0.222	-0.79 score on a scale Standard Error 0.211

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Stiffness Score	0.46 score on a scale Standard Error 3.139	-7.85 score on a scale Standard Error 3.034

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Physical Function as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Physical Function as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline to Week 24 in the WOMAC Physical Function Score	1.79 score on a scale Standard Error 2.722	-3.11 score on a scale Standard Error 2.553

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.

Change from baseline to post-baseline visits in BPI-Q3 (Worst Pain) score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for BPI worst pain as the dependent variable, region, visit, treatment and visit by treatment as fixed factors, and baseline of BPI Worst Pain as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in BPI Worst Pain Score Change at Week 12	-0.37 score on a scale Standard Error 0.216	-0.62 score on a scale Standard Error 0.208
Change From Baseline Over Time in BPI Worst Pain Score Change at Week 24	-0.31 score on a scale Standard Error 0.242	-0.77 score on a scale Standard Error 0.228
Change From Baseline Over Time in BPI Worst Pain Score Change at Week 36	-1.25 score on a scale Standard Error 0.234	-0.95 score on a scale Standard Error 0.228
Change From Baseline Over Time in BPI Worst Pain Score Change at Week 48	-1.49 score on a scale Standard Error 0.243	-1.05 score on a scale Standard Error 0.230
Change From Baseline Over Time in BPI Worst Pain Score Change at Week 72	-1.28 score on a scale Standard Error 0.283	-1.21 score on a scale Standard Error 0.316
Change From Baseline Over Time in BPI Worst Pain Score Change at Week 96	-0.99 score on a scale Standard Error 0.265	-1.48 score on a scale Standard Error 0.299

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

Change from baseline to post-baseline visits in BPI pain severity score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). The severity of pain in the last 24 hours is rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for each BPI endpoint as the dependent variable, region, visit, treatment, and visit by treatment as fixed factors, and baseline of each BPI endpoint as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in BPI Pain Severity Score Change at Week 24	-0.10 score on a scale Standard Error 0.211	-0.53 score on a scale Standard Error 0.172
Change From Baseline Over Time in BPI Pain Severity Score Change at Week 12	-0.32 score on a scale Standard Error 0.166	-0.43 score on a scale Standard Error 0.163
Change From Baseline Over Time in BPI Pain Severity Score Change at Week 36	-0.97 score on a scale Standard Error 0.214	-0.62 score on a scale Standard Error 0.184
Change From Baseline Over Time in BPI Pain Severity Score Change at Week 48	-1.13 score on a scale Standard Error 0.205	-0.79 score on a scale Standard Error 0.162
Change From Baseline Over Time in BPI Pain Severity Score Change at Week 72	-1.36 score on a scale Standard Error 0.216	-1.24 score on a scale Standard Error 0.231
Change From Baseline Over Time in BPI Pain Severity Score Change at Week 96	-1.18 score on a scale Standard Error 0.195	-1.42 score on a scale Standard Error 0.229

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

Change from baseline to post-baseline visits in BPI pain interference score as recorded on the day of the study visit. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Pain interference in the last 24 hours is rated on a scale of 0 (does not interfere) to 10 (completely interferes). The GEE Estimates are from the GEE model which includes the change from baseline for each BPI endpoint as the dependent variable, region, visit, treatment, and visit by treatment as fixed factors, and baseline of each BPI endpoint as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in BPI Pain Interference Score Change at Week 12	-0.29 score on a scale Standard Error 0.215	-0.51 score on a scale Standard Error 0.207
Change From Baseline Over Time in BPI Pain Interference Score Change at Week 24	-0.28 score on a scale Standard Error 0.242	-0.41 score on a scale Standard Error 0.207
Change From Baseline Over Time in BPI Pain Interference Score Change at Week 36	-1.30 score on a scale Standard Error 0.260	-0.79 score on a scale Standard Error 0.221
Change From Baseline Over Time in BPI Pain Interference Score Change at Week 48	-1.28 score on a scale Standard Error 0.251	-1.04 score on a scale Standard Error 0.235
Change From Baseline Over Time in BPI Pain Interference Score Change at Week 72	-1.22 score on a scale Standard Error 0.247	-1.24 score on a scale Standard Error 0.263
Change From Baseline Over Time in BPI Pain Interference Score Change at Week 96	-1.08 score on a scale Standard Error 0.260	-1.43 score on a scale Standard Error 0.234

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144

The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in WOMAC Stiffness Score Change at Week 24	0.20 score on a scale Standard Error 3.289	-8.01 score on a scale Standard Error 2.968
Change From Baseline Over Time in WOMAC Stiffness Score Change at Week 120	-19.23 score on a scale Standard Error 3.404	-20.57 score on a scale Standard Error 3.371
Change From Baseline Over Time in WOMAC Stiffness Score Change at Week 12	-1.24 score on a scale Standard Error 2.929	-7.86 score on a scale Standard Error 3.622
Change From Baseline Over Time in WOMAC Stiffness Score Change at Week 36	-13.50 score on a scale Standard Error 3.422	-12.58 score on a scale Standard Error 3.411
Change From Baseline Over Time in WOMAC Stiffness Score Change at Week 48	-15.83 score on a scale Standard Error 3.488	-16.63 score on a scale Standard Error 3.302
Change From Baseline Over Time in WOMAC Stiffness Score Change at Week 72	-18.02 score on a scale Standard Error 3.613	-15.47 score on a scale Standard Error 3.111
Change From Baseline Over Time in WOMAC Stiffness Score Change at Week 96	-17.67 score on a scale Standard Error 3.737	-15.32 score on a scale Standard Error 3.577
Change From Baseline Over Time in WOMAC Stiffness Score Change at Week 144	-30.64 score on a scale Standard Error 4.407	-25.88 score on a scale Standard Error 4.501

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144

The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in WOMAC Physical Function Score Change at Week 12	-1.40 score on a scale Standard Error 2.418	-3.96 score on a scale Standard Error 1.787
Change From Baseline Over Time in WOMAC Physical Function Score Change at Week 24	1.14 score on a scale Standard Error 2.531	-3.45 score on a scale Standard Error 2.193
Change From Baseline Over Time in WOMAC Physical Function Score Change at Week 36	-5.47 score on a scale Standard Error 2.694	-7.14 score on a scale Standard Error 2.133
Change From Baseline Over Time in WOMAC Physical Function Score Change at Week 48	-7.15 score on a scale Standard Error 2.801	-8.42 score on a scale Standard Error 2.057
Change From Baseline Over Time in WOMAC Physical Function Score Change at Week 72	-8.68 score on a scale Standard Error 2.835	-8.66 score on a scale Standard Error 2.523
Change From Baseline Over Time in WOMAC Physical Function Score Change at Week 96	-8.41 score on a scale Standard Error 2.752	-9.02 score on a scale Standard Error 2.270
Change From Baseline Over Time in WOMAC Physical Function Score Change at Week 120	-11.93 score on a scale Standard Error 2.685	-11.98 score on a scale Standard Error 2.291
Change From Baseline Over Time in WOMAC Physical Function Score Change at Week 144	-19.49 score on a scale Standard Error 3.892	-17.67 score on a scale Standard Error 4.061

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

Change from baseline to post-baseline visits in Brief Fatigue Inventory Question 3 (Worst Fatigue in Past 24 Hours; BFI-Q3) as averaged from daily diary scores recorded over 1 week and the study visit score. The BFI is a self-reported questionnaire consisting of 9 items related to fatigue rated on a 0 to 10 numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). Participants are asked to rate their worst fatigue over the past 24 hours from 0 (no fatigue) to 10 (as bad a you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for each BFI endpoint as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of each BFI endpoint as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in BFI Worst Fatigue Score Change at Week 96	-0.82 score on a scale Standard Error 0.362	-0.75 score on a scale Standard Error 0.306
Change From Baseline Over Time in BFI Worst Fatigue Score Change at Week 12	-0.53 score on a scale Standard Error 0.266	-0.44 score on a scale Standard Error 0.261
Change From Baseline Over Time in BFI Worst Fatigue Score Change at Week 24	-0.45 score on a scale Standard Error 0.298	-0.65 score on a scale Standard Error 0.280
Change From Baseline Over Time in BFI Worst Fatigue Score Change at Week 36	-1.23 score on a scale Standard Error 0.305	-0.90 score on a scale Standard Error 0.271
Change From Baseline Over Time in BFI Worst Fatigue Score Change at Week 48	-1.21 score on a scale Standard Error 0.317	-0.99 score on a scale Standard Error 0.295
Change From Baseline Over Time in BFI Worst Fatigue Score Change at Week 72	-0.79 score on a scale Standard Error 0.352	-0.58 score on a scale Standard Error 0.309

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

Change from baseline to post-baseline visits in BFI global fatigue score, calculated by averaging all 9 BFI items as recorded on the day of the study visit. The BFI is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). BFI Global Fatigue score was calculated by averaging all 9 items on the BFI. Global scores range from 0 to 10, with higher score indicating worse fatigue severity and interference. The GEE Estimates are from the GEE model which includes the change from baseline for each BFI endpoint as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of each BFI endpoint as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in BFI Global Fatigue Score Change at Week 12	-0.14 score on a scale Standard Error 0.262	-0.18 score on a scale Standard Error 0.261
Change From Baseline Over Time in BFI Global Fatigue Score Change at Week 24	-0.08 score on a scale Standard Error 0.292	0.05 score on a scale Standard Error 0.261
Change From Baseline Over Time in BFI Global Fatigue Score Change at Week 36	-0.69 score on a scale Standard Error 0.315	-0.54 score on a scale Standard Error 0.283
Change From Baseline Over Time in BFI Global Fatigue Score Change at Week 48	-0.75 score on a scale Standard Error 0.303	-0.45 score on a scale Standard Error 0.275
Change From Baseline Over Time in BFI Global Fatigue Score Change at Week 72	-0.72 score on a scale Standard Error 0.304	-0.78 score on a scale Standard Error 0.266
Change From Baseline Over Time in BFI Global Fatigue Score Change at Week 96	-0.86 score on a scale Standard Error 0.291	-0.80 score on a scale Standard Error 0.285

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=67 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) Change at Week 12	-1.86 ng/mL Standard Error 5.958	96.22 ng/mL Standard Error 14.264
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) Change at Week 24	2.95 ng/mL Standard Error 6.423	63.50 ng/mL Standard Error 7.239
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) Change at Week 36	100.00 ng/mL Standard Error 10.562	49.71 ng/mL Standard Error 6.786
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) Change at Week 48	85.12 ng/mL Standard Error 11.037	40.07 ng/mL Standard Error 7.292
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) Change at Week 72	48.98 ng/mL Standard Error 7.286	18.04 ng/mL Standard Error 9.186
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) Change at Week 96	22.98 ng/mL Standard Error 7.075	12.48 ng/mL Standard Error 8.661

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=67 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP Change at Week 96	41.62 percentage change Standard Error 8.163	31.04 percentage change Standard Error 8.126
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP Change at Week 12	2.30 percentage change Standard Error 6.318	91.78 percentage change Standard Error 10.787
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP Change at Week 24	7.83 percentage change Standard Error 7.076	72.43 percentage change Standard Error 8.519
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP Change at Week 36	116.39 percentage change Standard Error 9.726	63.58 percentage change Standard Error 8.562
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP Change a Week 48	99.10 percentage change Standard Error 11.442	56.51 percentage change Standard Error 8.771
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP Change at Week 72	72.56 percentage change Standard Error 10.055	38.82 percentage change Standard Error 10.225

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

The GEE Estimates are from the GEE model which includes the change from baseline for CTx as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=67 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) Change at Week 12	26.96 pg/mL Standard Error 35.689	322.09 pg/mL Standard Error 56.924
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) Change at Week 24	-4.20 pg/mL Standard Error 34.835	184.56 pg/mL Standard Error 39.213
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) Change at Week 36	350.89 pg/mL Standard Error 53.131	193.50 pg/mL Standard Error 39.461
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) Change at Week 48	310.67 pg/mL Standard Error 45.003	138.61 pg/mL Standard Error 37.886
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) Change at Week 72	178.03 pg/mL Standard Error 42.702	51.59 pg/mL Standard Error 42.863
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) Change at Week 96	79.04 pg/mL Standard Error 45.622	10.84 pg/mL Standard Error 40.761

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

The GEE Estimates are from the GEE model which includes the percent change from baseline for CTx as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=67 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx Change at Week 12	9.64 percentage change Standard Error 5.671	45.40 percentage change Standard Error 7.267
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx Change at Week 24	4.75 percentage change Standard Error 5.280	32.48 percentage change Standard Error 6.414
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx Change at Week 36	61.31 percentage change Standard Error 10.653	34.07 percentage change Standard Error 6.250
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx Change at Week 48	50.35 percentage change Standard Error 6.464	28.33 percentage change Standard Error 5.354
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx Change at Week 72	34.78 percentage change Standard Error 7.007	17.09 percentage change Standard Error 5.957
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx Change at Week 96	27.38 percentage change Standard Error 7.783	13.47 percentage change Standard Error 5.952

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

The GEE Estimates are from the GEE model which includes the change from baseline for BALP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of BALP as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=66 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) Change at Week 12	-2.11 μg/L Standard Error 1.529	6.52 μg/L Standard Error 2.832
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) Change at Week 24	1.03 μg/L Standard Error 1.801	5.70 μg/L Standard Error 2.038
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) Change at Week 36	10.42 μg/L Standard Error 2.017	4.46 μg/L Standard Error 1.607
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) Change at Week 48	6.69 μg/L Standard Error 1.929	0.23 μg/L Standard Error 1.830
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) Change at Week 72	-0.92 μg/L Standard Error 1.779	-3.39 μg/L Standard Error 1.739
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) Change at Week 96	-2.49 μg/L Standard Error 1.887	-2.76 μg/L Standard Error 1.640

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 24, 36, 48, 72, 96

The GEE Estimates are from the GEE model which includes the percent change from baseline for BALP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=66 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP Change at Week 36	64.41 percentage change Standard Error 11.669	43.13 percentage change Standard Error 11.473
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP Change at Week 48	50.65 percentage change Standard Error 11.317	23.46 percentage change Standard Error 10.041
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP Change at Week 12	7.85 percentage change Standard Error 9.867	30.29 percentage change Standard Error 13.476
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP Change at Week 24	27.56 percentage change Standard Error 10.339	39.13 percentage change Standard Error 10.902
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP Change at Week 72	19.79 percentage change Standard Error 11.755	14.40 percentage change Standard Error 11.618
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP Change at Week 96	16.46 percentage change Standard Error 11.027	21.21 percentage change Standard Error 9.688

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 4, 6, 10, 12, 14, 18, 20, 21, 22, 24, 26, 28, 34, 36, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144

The GEE Estimates are from the GEE model which includes the change from baseline for serum phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of serum phosphorus as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in Serum Phosphorus Change at Week 1	-0.01 mmol/L Standard Error 0.024	0.44 mmol/L Standard Error 0.031
Change From Baseline Over Time in Serum Phosphorus Change at Week 2	-0.03 mmol/L Standard Error 0.023	0.43 mmol/L Standard Error 0.032
Change From Baseline Over Time in Serum Phosphorus Change at Week 4	-0.03 mmol/L Standard Error 0.022	0.27 mmol/L Standard Error 0.034
Change From Baseline Over Time in Serum Phosphorus Change at Week 6	-0.00 mmol/L Standard Error 0.023	0.45 mmol/L Standard Error 0.036
Change From Baseline Over Time in Serum Phosphorus Change at Week 10	0.01 mmol/L Standard Error 0.022	0.37 mmol/L Standard Error 0.033
Change From Baseline Over Time in Serum Phosphorus Change at Week 12	-0.01 mmol/L Standard Error 0.023	0.17 mmol/L Standard Error 0.032
Change From Baseline Over Time in Serum Phosphorus Change at Week 14	0.02 mmol/L Standard Error 0.022	0.32 mmol/L Standard Error 0.032
Change From Baseline Over Time in Serum Phosphorus Change at Week 18	0.02 mmol/L Standard Error 0.023	0.32 mmol/L Standard Error 0.031
Change From Baseline Over Time in Serum Phosphorus Change at Week 20	-0.01 mmol/L Standard Error 0.023	0.18 mmol/L Standard Error 0.028
Change From Baseline Over Time in Serum Phosphorus Change at Week 21	-0.00 mmol/L Standard Error 0.024	0.31 mmol/L Standard Error 0.033
Change From Baseline Over Time in Serum Phosphorus Change at Week 22	-0.02 mmol/L Standard Error 0.022	0.25 mmol/L Standard Error 0.033
Change From Baseline Over Time in Serum Phosphorus Change at Week 24	-0.00 mmol/L Standard Error 0.023	0.13 mmol/L Standard Error 0.028
Change From Baseline Over Time in Serum Phosphorus Change at Week 26	0.47 mmol/L Standard Error 0.035	0.31 mmol/L Standard Error 0.032
Change From Baseline Over Time in Serum Phosphorus Change at Week 28	0.28 mmol/L Standard Error 0.028	0.18 mmol/L Standard Error 0.028
Change From Baseline Over Time in Serum Phosphorus Change at Week 34	0.36 mmol/L Standard Error 0.029	0.28 mmol/L Standard Error 0.031
Change From Baseline Over Time in Serum Phosphorus Change at Week 36	0.17 mmol/L Standard Error 0.026	0.13 mmol/L Standard Error 0.027
Change From Baseline Over Time in Serum Phosphorus Change at Week 46	0.31 mmol/L Standard Error 0.026	0.27 mmol/L Standard Error 0.030
Change From Baseline Over Time in Serum Phosphorus Change at Week 48	0.13 mmol/L Standard Error 0.027	0.11 mmol/L Standard Error 0.027
Change From Baseline Over Time in Serum Phosphorus Change at Week 60	0.14 mmol/L Standard Error 0.028	0.11 mmol/L Standard Error 0.028
Change From Baseline Over Time in Serum Phosphorus Change at Week 70	0.30 mmol/L Standard Error 0.029	0.30 mmol/L Standard Error 0.030
Change From Baseline Over Time in Serum Phosphorus Change at Week 72	0.13 mmol/L Standard Error 0.025	0.11 mmol/L Standard Error 0.027
Change From Baseline Over Time in Serum Phosphorus Change at Week 84	0.12 mmol/L Standard Error 0.025	0.14 mmol/L Standard Error 0.027
Change From Baseline Over Time in Serum Phosphorus Change at Week 94	0.25 mmol/L Standard Error 0.029	0.30 mmol/L Standard Error 0.029
Change From Baseline Over Time in Serum Phosphorus Change at Week 96	0.07 mmol/L Standard Error 0.026	0.13 mmol/L Standard Error 0.025
Change From Baseline Over Time in Serum Phosphorus Change at Week 108	0.11 mmol/L Standard Error 0.028	0.13 mmol/L Standard Error 0.031
Change From Baseline Over Time in Serum Phosphorus Change at Week 120	0.09 mmol/L Standard Error 0.027	0.13 mmol/L Standard Error 0.033
Change From Baseline Over Time in Serum Phosphorus Change at Week 132	0.12 mmol/L Standard Error 0.033	0.15 mmol/L Standard Error 0.036
Change From Baseline Over Time in Serum Phosphorus Change at Week 144	0.05 mmol/L Standard Error 0.064	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 4, 6, 10, 12, 14, 18, 20, 21, 22, 24, 26, 28, 34, 36, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144

The GEE Estimates are from the GEE model which includes the percent change from baseline for serum phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of serum phosphorus as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 6	-0.41 percentage change Standard Error 3.951	72.96 percentage change Standard Error 5.944
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 12	-2.14 percentage change Standard Error 3.798	29.50 percentage change Standard Error 5.087
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 14	3.58 percentage change Standard Error 3.691	52.14 percentage change Standard Error 5.194
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 18	3.93 percentage change Standard Error 3.857	53.22 percentage change Standard Error 5.106
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 20	-1.81 percentage change Standard Error 3.759	31.28 percentage change Standard Error 4.472
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 21	0.21 percentage change Standard Error 4.011	50.59 percentage change Standard Error 5.123
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 22	-3.42 percentage change Standard Error 3.709	40.98 percentage change Standard Error 5.196
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 24	-0.61 percentage change Standard Error 3.802	22.01 percentage change Standard Error 4.523
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 26	78.30 percentage change Standard Error 5.993	51.51 percentage change Standard Error 5.204
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 28	46.07 percentage change Standard Error 4.766	31.32 percentage change Standard Error 4.415
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 34	59.18 percentage change Standard Error 4.959	45.83 percentage change Standard Error 4.871
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 36	28.03 percentage change Standard Error 4.424	22.34 percentage change Standard Error 4.256
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 46	51.49 percentage change Standard Error 4.380	45.39 percentage change Standard Error 5.018
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 48	21.58 percentage change Standard Error 4.365	19.12 percentage change Standard Error 4.190
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 60	22.90 percentage change Standard Error 4.338	19.60 percentage change Standard Error 4.436
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 70	50.22 percentage change Standard Error 4.916	47.81 percentage change Standard Error 4.768
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 72	21.59 percentage change Standard Error 4.155	19.45 percentage change Standard Error 4.344
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 84	21.47 percentage change Standard Error 4.089	23.58 percentage change Standard Error 4.200
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 94	43.67 percentage change Standard Error 4.834	49.36 percentage change Standard Error 4.501
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 96	12.97 percentage change Standard Error 4.216	21.65 percentage change Standard Error 3.854
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 108	19.21 percentage change Standard Error 4.665	23.39 percentage change Standard Error 4.749
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 120	15.13 percentage change Standard Error 4.365	21.50 percentage change Standard Error 5.268
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 132	20.43 percentage change Standard Error 5.362	25.34 percentage change Standard Error 5.847
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 144	5.49 percentage change Standard Error 12.212	—
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 1	-1.11 percentage change Standard Error 3.936	69.24 percentage change Standard Error 4.762
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 2	-5.91 percentage change Standard Error 3.969	69.39 percentage change Standard Error 4.881
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 4	-4.84 percentage change Standard Error 3.792	42.89 percentage change Standard Error 5.325
Percent Change From Baseline Over Time in Serum Phosphorus Change at Week 10	2.40 percentage change Standard Error 3.680	59.96 percentage change Standard Error 5.356

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144

The GEE Estimates are from the GEE model which includes the change from baseline for 1,25(OH)2D as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo SC Q4W through Week 24	Burosumab n=66 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 1	2.04 pg/mL Standard Error 2.251	87.23 pg/mL Standard Error 5.500
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 2	1.40 pg/mL Standard Error 2.113	58.20 pg/mL Standard Error 3.931
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 4	2.61 pg/mL Standard Error 2.300	20.55 pg/mL Standard Error 2.828
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 20	2.88 pg/mL Standard Error 2.163	8.11 pg/mL Standard Error 2.294
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 21	3.09 pg/mL Standard Error 2.177	33.95 pg/mL Standard Error 3.019
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 22	3.45 pg/mL Standard Error 2.289	26.10 pg/mL Standard Error 2.952
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 46	25.23 pg/mL Standard Error 2.576	23.08 pg/mL Standard Error 3.243
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 48	10.50 pg/mL Standard Error 2.418	7.24 pg/mL Standard Error 2.449
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 60	9.29 pg/mL Standard Error 2.336	5.69 pg/mL Standard Error 2.583
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 70	24.20 pg/mL Standard Error 2.529	18.82 pg/mL Standard Error 2.486
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 72	7.12 pg/mL Standard Error 2.424	5.52 pg/mL Standard Error 2.607
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 84	5.13 pg/mL Standard Error 2.388	1.16 pg/mL Standard Error 2.549
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 94	18.96 pg/mL Standard Error 2.655	15.26 pg/mL Standard Error 2.502
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 96	3.43 pg/mL Standard Error 2.348	1.95 pg/mL Standard Error 2.356
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 108	4.76 pg/mL Standard Error 2.349	4.29 pg/mL Standard Error 2.672
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 120	4.64 pg/mL Standard Error 2.496	5.37 pg/mL Standard Error 2.935
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 132	4.08 pg/mL Standard Error 3.142	8.05 pg/mL Standard Error 4.227
Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 144	-0.38 pg/mL Standard Error 4.677	—

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144

The GEE Estimates are from the GEE model which includes the percent change from baseline for 1,25(OH)2D as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo SC Q4W through Week 24	Burosumab n=66 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 4	16.07 percentage change Standard Error 12.810	76.22 percentage change Standard Error 12.147
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 1	10.45 percentage change Standard Error 13.041	310.72 percentage change Standard Error 23.225
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 2	10.53 percentage change Standard Error 12.760	207.90 percentage change Standard Error 16.728
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 20	21.36 percentage change Standard Error 12.424	41.08 percentage change Standard Error 11.943
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 21	21.51 percentage change Standard Error 12.825	131.76 percentage change Standard Error 14.862
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 22	21.07 percentage change Standard Error 12.725	102.81 percentage change Standard Error 14.619
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 46	130.29 percentage change Standard Error 22.718	96.63 percentage change Standard Error 16.909
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 48	70.09 percentage change Standard Error 17.114	34.47 percentage change Standard Error 12.903
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 60	65.46 percentage change Standard Error 13.083	32.32 percentage change Standard Error 12.230
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 70	123.58 percentage change Standard Error 17.315	82.03 percentage change Standard Error 12.604
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 72	58.45 percentage change Standard Error 13.957	31.14 percentage change Standard Error 13.070
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 84	55.67 percentage change Standard Error 15.323	18.83 percentage change Standard Error 12.801
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 94	111.25 percentage change Standard Error 21.970	71.30 percentage change Standard Error 12.280
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 96	50.17 percentage change Standard Error 18.857	22.15 percentage change Standard Error 10.487
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 108	44.78 percentage change Standard Error 14.219	29.16 percentage change Standard Error 13.326
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 120	58.37 percentage change Standard Error 19.621	36.09 percentage change Standard Error 13.089
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 132	67.59 percentage change Standard Error 35.770	42.55 percentage change Standard Error 15.925
Percent Change From Baseline Over Time in Serum 1,25(OH)2D Change at Week 144	22.65 percentage change Standard Error 19.297	—

SECONDARY outcome

Timeframe: Baseline, Week 12, 24, 36, 48, 72, 96

The GEE Estimates are from the GEE model which includes the change from baseline for 24-Hour urinary phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of urinary phosphorus as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Placebo SC Q4W through Week 24	Burosumab n=67 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 12	0.06 g/24 hour Standard Error 0.052	0.05 g/24 hour Standard Error 0.046
Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 24	0.07 g/24 hour Standard Error 0.065	0.05 g/24 hour Standard Error 0.046
Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 36	0.04 g/24 hour Standard Error 0.054	0.07 g/24 hour Standard Error 0.045
Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 48	0.07 g/24 hour Standard Error 0.060	0.13 g/24 hour Standard Error 0.067
Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 72	0.08 g/24 hour Standard Error 0.065	0.05 g/24 hour Standard Error 0.052
Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 96	0.10 g/24 hour Standard Error 0.075	0.10 g/24 hour Standard Error 0.054

SECONDARY outcome

Timeframe: Baseline, Week 12, 24, 36, 48, 72, 96

The GEE Estimates are from the GEE model which includes the percent change from baseline for 24-hour urinary phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of urinary phosphorus as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=65 Participants Placebo SC Q4W through Week 24	Burosumab n=67 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 12	21.91 percentage change Standard Error 11.844	21.40 percentage change Standard Error 11.453
Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 24	28.45 percentage change Standard Error 15.518	20.35 percentage change Standard Error 11.567
Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 36	18.19 percentage change Standard Error 11.784	28.31 percentage change Standard Error 12.173
Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 48	27.32 percentage change Standard Error 14.328	37.50 percentage change Standard Error 14.687
Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 72	29.53 percentage change Standard Error 14.485	25.80 percentage change Standard Error 15.476
Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus Change at Week 96	31.17 percentage change Standard Error 17.248	30.64 percentage change Standard Error 10.420

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96

The GEE Estimates are from the GEE model which includes the change from baseline for TmP/GFR as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Placebo SC Q4W through Week 24	Burosumab n=66 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 2	-0.02 mg/dL Standard Error 0.072	1.60 mg/dL Standard Error 0.121
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 4	-0.03 mg/dL Standard Error 0.070	0.91 mg/dL Standard Error 0.117
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 12	0.11 mg/dL Standard Error 0.082	0.70 mg/dL Standard Error 0.107
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 22	0.02 mg/dL Standard Error 0.069	1.01 mg/dL Standard Error 0.123
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 24	0.07 mg/dL Standard Error 0.071	0.51 mg/dL Standard Error 0.093
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 48	0.55 mg/dL Standard Error 0.087	0.48 mg/dL Standard Error 0.091
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 60	0.57 mg/dL Standard Error 0.097	0.43 mg/dL Standard Error 0.086
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 72	0.55 mg/dL Standard Error 0.086	0.43 mg/dL Standard Error 0.091
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 84	0.49 mg/dL Standard Error 0.078	0.42 mg/dL Standard Error 0.092
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) Change at Week 96	0.29 mg/dL Standard Error 0.086	0.46 mg/dL Standard Error 0.084

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96

The GEE Estimates are from the GEE model which includes the percent change from baseline for TmP/GFR as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants Placebo SC Q4W through Week 24	Burosumab n=66 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline Over Time in TmP/GFR Change at Week 2	-2.15 percentage change Standard Error 4.515	100.10 percentage change Standard Error 7.222
Percent Change From Baseline Over Time in TmP/GFR Change at Week 4	-2.73 percentage change Standard Error 4.416	56.53 percentage change Standard Error 6.816
Percent Change From Baseline Over Time in TmP/GFR Change at Week 12	6.28 percentage change Standard Error 4.900	43.65 percentage change Standard Error 6.206
Percent Change From Baseline Over Time in TmP/GFR Change at Week 22	1.38 percentage change Standard Error 4.252	62.38 percentage change Standard Error 7.144
Percent Change From Baseline Over Time in TmP/GFR Change at Week 24	3.63 percentage change Standard Error 4.460	33.02 percentage change Standard Error 5.464
Percent Change From Baseline Over Time in TmP/GFR Change at Week 48	35.52 percentage change Standard Error 5.390	31.02 percentage change Standard Error 5.489
Percent Change From Baseline Over Time in TmP/GFR Change at Week 60	37.13 percentage change Standard Error 5.855	27.49 percentage change Standard Error 5.002
Percent Change From Baseline Over Time in TmP/GFR Change at Week 72	35.89 percentage change Standard Error 5.492	28.98 percentage change Standard Error 5.513
Percent Change From Baseline Over Time in TmP/GFR Change at Week 84	33.15 percentage change Standard Error 4.924	27.69 percentage change Standard Error 5.527
Percent Change From Baseline Over Time in TmP/GFR Change at Week 96	19.95 percentage change Standard Error 5.417	29.67 percentage change Standard Error 4.759

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96

The GEE Estimates are from the GEE model which includes the change from baseline for TRP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo SC Q4W through Week 24	Burosumab n=67 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 48	0.02 fraction of phosphate reabsorbed Standard Error 0.012	0.03 fraction of phosphate reabsorbed Standard Error 0.009
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 84	0.02 fraction of phosphate reabsorbed Standard Error 0.010	0.01 fraction of phosphate reabsorbed Standard Error 0.012
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 2	-0.02 fraction of phosphate reabsorbed Standard Error 0.013	0.07 fraction of phosphate reabsorbed Standard Error 0.008
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 4	-0.03 fraction of phosphate reabsorbed Standard Error 0.012	0.03 fraction of phosphate reabsorbed Standard Error 0.009
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 12	-0.00 fraction of phosphate reabsorbed Standard Error 0.010	0.04 fraction of phosphate reabsorbed Standard Error 0.008
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 22	-0.01 fraction of phosphate reabsorbed Standard Error 0.009	0.05 fraction of phosphate reabsorbed Standard Error 0.011
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 24	-0.02 fraction of phosphate reabsorbed Standard Error 0.012	0.03 fraction of phosphate reabsorbed Standard Error 0.009
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 60	0.03 fraction of phosphate reabsorbed Standard Error 0.009	0.02 fraction of phosphate reabsorbed Standard Error 0.009
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 72	0.02 fraction of phosphate reabsorbed Standard Error 0.011	0.02 fraction of phosphate reabsorbed Standard Error 0.011
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) Change at Week 96	-0.01 fraction of phosphate reabsorbed Standard Error 0.014	0.03 fraction of phosphate reabsorbed Standard Error 0.009

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96

The GEE Estimates are from the GEE model which includes the percent change from baseline for TRP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Placebo SC Q4W through Week 24	Burosumab n=67 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline Over Time in TRP Change at Week 2	-2.00 percentage change Standard Error 1.530	9.81 percentage change Standard Error 1.111
Percent Change From Baseline Over Time in TRP Change at Week 24	-1.56 percentage change Standard Error 1.579	4.21 percentage change Standard Error 1.141
Percent Change From Baseline Over Time in TRP Change at Week 48	3.95 percentage change Standard Error 1.547	4.70 percentage change Standard Error 1.183
Percent Change From Baseline Over Time in TRP Change at Week 60	3.99 percentage change Standard Error 1.096	3.00 percentage change Standard Error 1.123
Percent Change From Baseline Over Time in TRP Change at Week 72	3.90 percentage change Standard Error 1.427	3.24 percentage change Standard Error 1.414
Percent Change From Baseline Over Time in TRP Change at Week 4	-3.75 percentage change Standard Error 1.486	4.86 percentage change Standard Error 1.114
Percent Change From Baseline Over Time in TRP Change at Week 84	3.78 percentage change Standard Error 1.276	1.97 percentage change Standard Error 1.516
Percent Change From Baseline Over Time in TRP Change at Week 96	-0.09 percentage change Standard Error 1.582	4.44 percentage change Standard Error 1.116
Percent Change From Baseline Over Time in TRP Change at Week 12	0.56 percentage change Standard Error 1.261	5.45 percentage change Standard Error 1.079
Percent Change From Baseline Over Time in TRP Change at Week 22	-0.01 percentage change Standard Error 1.163	7.03 percentage change Standard Error 1.451

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24	6.1 percentage of participants Interval 2.4 to 14.6	67.6 percentage of participants Interval 55.8 to 77.6

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24	0.16 mg/dL Standard Deviation 0.272	1.21 mg/dL Standard Deviation 0.513

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24	9.85 percentage change Standard Deviation 15.292	61.44 percentage change Standard Deviation 28.961

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24	0.13 mg/dL Standard Deviation 0.265	0.69 mg/dL Standard Deviation 0.392

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Percent Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24	7.83 percentage change Standard Deviation 14.755	35.18 percentage change Standard Deviation 20.731

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.

Outcome measures

Outcome measures
Measure	Placebo n=66 Participants Placebo SC Q4W through Week 24	Burosumab n=68 Participants Burosumab 1 mg/kg SC Q4W
Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24	2.08 mg/dL Standard Deviation 0.292	3.08 mg/dL Standard Deviation 0.477

Adverse Events

Placebo (DB Period)

Serious events: 1 serious events

Other events: 57 other events

Deaths: 0 deaths

Placebo -> Burosumab (OL Period)

Serious events: 10 serious events

Other events: 63 other events

Deaths: 0 deaths

Burosumab -> Burosumab (Combined DB and OL Period)

Serious events: 12 serious events

Other events: 68 other events

Deaths: 1 deaths

Total Burosumab (Combined DB and OL Period)

Serious events: 22 serious events

Other events: 131 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information

Ultragenyx Pharmaceutical Inc

Phone: 1-888-756-8657

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Placebo (DB Period) n=66 participants at risk SC injection of placebo Q4W for 24 weeks (double-blind placebo-controlled Treatment Period)	Placebo -> Burosumab (OL Period) n=66 participants at risk SC injection of placebo Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II \[US only\]).	Burosumab -> Burosumab (Combined DB and OL Period) n=68 participants at risk SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II \[US only\]).	Total Burosumab (Combined DB and OL Period) n=134 participants at risk SC injection of 1.0 mg/kg burosumab at any time during the study.
Cardiac disorders Palpitations	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Colitis	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Duodenal Ulcer	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Ileus	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Irritable Bowel Syndrome	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Periodontal Disease	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Peritoneal Adhesions	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Hepatobiliary disorders Cholelithiasis	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Gastroenteritis	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Medical Device Site Infection	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Overdose	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Procedural Nausea	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Procedural Vomiting	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Subdural Haematoma	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 2/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Cervical Spinal Stenosis	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Joint Range Of Motion Decreased	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Knee Deformity	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Pseudarthrosis	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Spinal Column Stenosis	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive Ductal Breast Carcinoma	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid Tumour Benign	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Nervous system disorders Cerebrospinal Fluid Leakage	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Nervous system disorders Cervical Radiculopathy	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Nervous system disorders Dizziness	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Nervous system disorders Myelopathy	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	2.9% 2/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 2/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Nervous system disorders Neuralgia	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Nervous system disorders Paraesthesia	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Nervous system disorders Partial Seizures	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Nervous system disorders Presyncope	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.75% 1/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.

Other adverse events
Measure	Placebo (DB Period) n=66 participants at risk SC injection of placebo Q4W for 24 weeks (double-blind placebo-controlled Treatment Period)	Placebo -> Burosumab (OL Period) n=66 participants at risk SC injection of placebo Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II \[US only\]).	Burosumab -> Burosumab (Combined DB and OL Period) n=68 participants at risk SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II \[US only\]).	Total Burosumab (Combined DB and OL Period) n=134 participants at risk SC injection of 1.0 mg/kg burosumab at any time during the study.
Infections and infestations Sinusitis	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.8% 6/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.0% 8/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Tooth Abscess	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.6% 5/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	27.9% 19/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	17.9% 24/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Rhinitis	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.1% 4/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	3.7% 5/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Pharyngitis	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	3.0% 4/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Ear and labyrinth disorders Vertigo	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.1% 4/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.4% 3/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.2% 7/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Endocrine disorders Hyperparathyroidism Secondary	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.5% 3/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.2% 7/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.5% 3/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.2% 7/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Abdominal Pain	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.8% 6/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.0% 8/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.4% 3/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.7% 9/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Constipation	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.1% 4/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	14.7% 10/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	10.4% 14/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Diarrhoea	7.6% 5/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.6% 5/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	19.1% 13/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	13.4% 18/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Nausea	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.6% 5/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	16.2% 11/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	11.9% 16/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Toothache	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	15.2% 10/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	17.6% 12/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	16.4% 22/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Gastrointestinal disorders Vomiting	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.1% 4/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.8% 6/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.5% 10/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
General disorders Asthenia	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.4% 5/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.5% 6/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
General disorders Fatigue	10.6% 7/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	21.2% 14/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	23.5% 16/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	22.4% 30/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
General disorders Injection Site Erythema	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.8% 6/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.0% 12/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
General disorders Injection Site Pruritus	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	12.1% 8/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.4% 3/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.2% 11/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
General disorders Injection Site Reaction	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	12.1% 8/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	10.3% 7/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	11.2% 15/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
General disorders Pain	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	13.6% 9/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	17.6% 12/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	15.7% 21/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
General disorders Pyrexia	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.1% 4/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.4% 5/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.7% 9/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Immune system disorders Seasonal Allergy	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.4% 5/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.2% 11/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Bronchitis	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.5% 10/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Gastroenteritis	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.1% 4/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	2.9% 2/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.5% 6/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Influenza	4.5% 3/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	13.2% 9/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	11.2% 15/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Nasopharyngitis	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	36.4% 24/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	41.2% 28/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	38.8% 52/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Oral Herpes	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.1% 4/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.0% 8/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Upper Respiratory Tract Infection	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	17.6% 12/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	10.4% 14/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Infections and infestations Urinary Tract Infection	6.1% 4/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.4% 5/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.2% 11/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Contusion	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.6% 5/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.7% 9/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Fall	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	10.6% 7/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.8% 6/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.7% 13/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Ligament Sprain	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	3.0% 2/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.5% 6/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Injury, poisoning and procedural complications Procedural Pain	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	9.1% 6/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	13.2% 9/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	11.2% 15/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Investigations Blood 25-Hydroxycholecalciferol Decreased	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.5% 3/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.8% 6/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	6.7% 9/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Investigations Blood Glucose Increased	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.4% 5/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.5% 6/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Investigations Blood Parathyroid Hormone Increased	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	7.4% 5/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	4.5% 6/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Investigations Blood Pressure Increased	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	8.8% 6/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.2% 7/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Investigations Lipase Increased	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	3.0% 4/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Investigations Vitamin D Decreased	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	13.6% 9/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	11.8% 8/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	12.7% 17/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.
Metabolism and nutrition disorders Decreased Appetite	1.5% 1/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	0.00% 0/66 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	5.9% 4/68 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.	3.0% 4/134 • From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.