Trial Outcomes & Findings for Safety and Efficacy Study of rhPTH(1-84) in Subjects With Hypoparathyroidism (NCT NCT03364738)

NCT ID: NCT03364738

Last Updated: 2022-10-07

Results Overview

Percentage of participants who achieved ACSC values \>= to range of 1.875 mmol/L and \<= ULN at Week 24 was reported.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 22 participants
• Primary outcome timeframe: At Week 24
• Results posted on: 2022-10-07

Participant Flow

Participants with hypoparathyroidism (HPT) who completed SHP634-101 (NCT02781844) study were eligible and enrolled in this extension study which was conducted at 10 sites in the United States, Denmark, Hungary and Canada between 26 September 2018 (first participant first visit) and 14 April 2020 (last participant last visit).

A total of 22 participants were enrolled and treated in the study, of which 14 participants completed the study.

Participant milestones

Measure	rhPTH(1-84) Participants received recombinant human parathyroid hormone (rhPTH) (1-84) (Natpara) 50 microgram (mcg), injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (end of treatment \[EOT\])/ early termination (ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining albumin-corrected serum calcium (ACSC) levels in the range of 2-2.25 millimoles per liter (mmol/L) (8-9 milligrams per deciliter \[mg/dL\]). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was greater than (\>) 2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Overall Study STARTED	22
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Measure	rhPTH(1-84) Participants received recombinant human parathyroid hormone (rhPTH) (1-84) (Natpara) 50 microgram (mcg), injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (end of treatment \[EOT\])/ early termination (ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining albumin-corrected serum calcium (ACSC) levels in the range of 2-2.25 millimoles per liter (mmol/L) (8-9 milligrams per deciliter \[mg/dL\]). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was greater than (\>) 2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Overall Study Early termination due to Food and Drug Administration recall of rhPTH(1-84) (Natpara)	6
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1

Baseline Characteristics

Safety and Efficacy Study of rhPTH(1-84) in Subjects With Hypoparathyroidism

Baseline characteristics by cohort

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Age, Continuous	50 years STANDARD_DEVIATION 11.39 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized White	20 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized Native American And Caucasian	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 24

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Percentage of participants who achieved ACSC values >= to range of 1.875 mmol/L and <= ULN at Week 24 was reported.

Outcome measures

Measure

rhPTH(1-84) n=21 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Percentage of Participants Who Achieved Total Albumin-corrected Serum Calcium (ACSC) Values Greater Than or Equal to (>=) to the Range of 7.5 mg/dL (1.875 mmol/L) and Less Than or Equal to (<=) Upper Limit of Normal (ULN) at Week 24

100 percentage of participants

PRIMARY outcome

Timeframe: At Week 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84).

Percentage of participants who achieved ACSC values >= to range of 1.875 mmol/L and <= ULN at Week 52 (EOT) was reported.

Outcome measures

Measure

rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Percentage of Participants With Total ACSC Values >= to the Range of 7.5 mg/dL (1.875 mmol/L) and <=ULN at Week 52 (End-of-treatment [EOT])

95.5 percentage of participants Interval 0.772 to 0.999

PRIMARY outcome

Timeframe: From start of study drug administration to end of study (Week 56)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84).

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, and is an important medical event. TEAEs were defined as AEs with a start date on or after the first dose of investigational product or a start date before the date of the first dose of investigational product that increased in severity or after the date of the first dose.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	17 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with serious TEAEs	4 Participants

PRIMARY outcome

Timeframe: From start of study drug administration to end of study (Week 56)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84).

Clinical laboratory assessment included hematology, serum chemistry, urine chemistry and urinalysis. Clinical significance was judged by the investigator based upon the out of range values of standard range set for each parameter. Any changes in clinical laboratory results which were deemed clinically significant by the investigator was reported.

Outcome measures

Measure

rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Number of Participants With Clinically Significant Change in Clinical Laboratory Values

0 Participants

PRIMARY outcome

Timeframe: From start of study drug administration to end of study (Week 56)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84).

Vital sign parameters included: temperature, pulse rate, respiration rate, systolic and diastolic blood pressure. Clinical significance was judged by the investigator based upon the out of range values of standard range set for each parameter. Any changes in vital signs which were deemed clinically significant by the investigator was reported.

Outcome measures

Measure

rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Number of Participants With Clinically Significant Change in Vital Sign

0 Participants

PRIMARY outcome

Timeframe: From start of study drug administration to end of study (Week 56)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84).

Twelve-lead ECGs was performed in triplicate with a minimum 2-minute gap between traces. The participant rested in the supine position for at least 5 minutes before collecting the ECG. Assessment of ECG parameters included: heart rate, RR interval, PR interval, QRS interval, QT interval, and QTc interval. Clinical significance was judged by the investigator based upon the out of range values of standard range set for each parameter. Any change in ECG assessments which were deemed clinically significant by the investigator was reported.

Outcome measures

Measure

rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters

0 Participants

PRIMARY outcome

Timeframe: From start of study drug administration to end of study (Week 56)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84).

eGFR was calculated using the chronic kidney disease epidemiology (CDK-epi) formula. Clinical significance was judged by the investigator based upon the out of range values of standard range set for parameter. Any change in eGFR assessments which were deemed clinically significant by the investigator was reported.

Outcome measures

Measure

rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Number of Participants With Clinically Significant Change in Estimated Glomerular Filtration Rate (eGFR) Values

0 Participants

PRIMARY outcome

Timeframe: From start of study drug administration to end of study (Week 56)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84).

eGFR was assessed by measuring serum creatinine. Serum creatinine level was obtained directly from laboratory results. Clinical significance was judged by the investigator based upon the out of range values of standard range set for parameter. Any change in serum creatinine assessments which were deemed clinically significant by the investigator was reported.

Outcome measures

Measure

rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Number of Participants With Clinically Significant Change in Serum Creatinine Value

0 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Number of participants with positive anti-parathyroid hormone antibodies at Week 24 was reported.

Outcome measures

Measure

rhPTH(1-84) n=21 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 24

0 Participants

PRIMARY outcome

Timeframe: Week 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure.

Number of participants with positive anti-parathyroid hormone antibodies at Week 52 (EOT) was reported.

Outcome measures

Measure

rhPTH(1-84) n=21 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.

Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 52 (EOT)

0 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Change from baseline in ACSC concentration at Weeks 24 and 52 (EOT) was reported.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Change From Baseline in Albumin Corrected Serum Calcium (ACSC) Concentration at Weeks 24 and 52 (EOT) Change at Week 24	-0.024 mmol/L Standard Deviation 0.2065
Change From Baseline in Albumin Corrected Serum Calcium (ACSC) Concentration at Weeks 24 and 52 (EOT) Change at Week 52 (EOT)	-0.076 mmol/L Standard Deviation 0.1497

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Change from baseline in serum phosphate concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) was reported.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 4	-0.167 mmol/L Standard Deviation 0.1816
Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 8	-0.124 mmol/L Standard Deviation 0.2252
Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 16	-0.107 mmol/L Standard Deviation 0.2583
Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 24	-0.160 mmol/L Standard Deviation 0.2303
Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 32	-0.089 mmol/L Standard Deviation 0.1809
Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 40	-0.121 mmol/L Standard Deviation 0.2542
Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 52 (EOT)	-0.114 mmol/L Standard Deviation 0.2590

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Change from baseline in ACSC-phosphate product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) was reported. Here "mmol^2/L^2" is abbreviated as millimoles square per liter square.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 4	-0.31 mmol^2/L^2 Standard Deviation 0.462
Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 8	-0.19 mmol^2/L^2 Standard Deviation 0.537
Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 16	-0.16 mmol^2/L^2 Standard Deviation 0.609
Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 24	-0.38 mmol^2/L^2 Standard Deviation 0.556
Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 32	-0.29 mmol^2/L^2 Standard Deviation 0.456
Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 40	-0.29 mmol^2/L^2 Standard Deviation 0.572
Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) Change at Week 52 (EOT)	-0.34 mmol^2/L^2 Standard Deviation 0.539

SECONDARY outcome

Timeframe: Baseline, Weeks 16, 32 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure and "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Change from baseline in 24-hour urine calcium excretion at Weeks 16, 32 and 52 (EOT) was reported.

Outcome measures

Measure	rhPTH(1-84) n=21 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Change From Baseline in 24-hour Urine Calcium Excretion at Weeks 16, 32 and 52 (EOT) Change at Week 16	-0.22 millimoles per day (mmol/day) Standard Deviation 4.741
Change From Baseline in 24-hour Urine Calcium Excretion at Weeks 16, 32 and 52 (EOT) Change at Week 32	-3.13 millimoles per day (mmol/day) Standard Deviation 4.103
Change From Baseline in 24-hour Urine Calcium Excretion at Weeks 16, 32 and 52 (EOT) Change at Week 52 (EOT)	-2.53 millimoles per day (mmol/day) Standard Deviation 4.421

SECONDARY outcome

Timeframe: Baseline and at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points. Data for Week 56 was not collected as study was early terminated due to FDA recall of rhPTH(1-84) (Natpara).

Percentage change from baseline in prescribed supplemental oral calcium dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) were reported.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS]) Percentage change at Week 8	-29.08 percentage change Standard Deviation 38.019
Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS]) Percentage change at Week 16	-36.94 percentage change Standard Deviation 45.665
Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS]) Percentage change at Week 4	-14.30 percentage change Standard Deviation 34.269
Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS]) Percentage change at Week 24	-49.05 percentage change Standard Deviation 49.049
Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS]) Percentage change at Week 32	-55.58 percentage change Standard Deviation 44.268
Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS]) Percentage change at Week 40	-56.36 percentage change Standard Deviation 45.168
Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS]) Percentage change at Week 52 (EOT)	-48.55 percentage change Standard Deviation 45.237

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "overall number of participants analyzed" were participants who were evaluable for this outcome measure and "number analyzed" were participants who were evaluable for the outcome measure at given time points. Data for Week 56 was not collected as study was early terminated due to FDA recall of rhPTH(1-84) (Natpara).

Percentage change from baseline in prescribed supplemental oral calcium dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) were reported.

Outcome measures

Measure	rhPTH(1-84) n=21 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) Percentage change at Week 4	-57.50 percentage change Standard Deviation 40.995
Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) Percentage change at Week 8	-70.00 percentage change Standard Deviation 39.217
Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) Percentage change at Week 16	-80.83 percentage change Standard Deviation 27.185
Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) Percentage change at Week 24	-85.42 percentage change Standard Deviation 25.055
Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) Percentage change at Week 32	-90.79 percentage change Standard Deviation 17.324
Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) Percentage change at Week 40	-90.10 percentage change Standard Deviation 18.564
Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) Percentage change at Week 52 (EOT)	-77.38 percentage change Standard Deviation 43.870

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 24 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Percentage change from baseline in serum bone-specific alkaline phosphatase at Weeks 8, 24 and 52 (EOT) was reported.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase at Weeks 8, 24 and 52 (EOT) Percentage change at Week 24	89.14 percentage change Standard Deviation 54.452
Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase at Weeks 8, 24 and 52 (EOT) Percentage change at Week 52 (EOT)	94.08 percentage change Standard Deviation 75.066
Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase at Weeks 8, 24 and 52 (EOT) Percentage change at Week 8	29.90 percentage change Standard Deviation 31.575

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 24 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Percentage change from baseline in serum osteocalcin at Weeks 8, 24 and 52 (EOT) was reported.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Percentage Change From Baseline in Serum Osteocalcin at Weeks 8, 24 and 52 (EOT) Percentage change at Week 8	61.74 percentage change Standard Deviation 68.363
Percentage Change From Baseline in Serum Osteocalcin at Weeks 8, 24 and 52 (EOT) Percentage change at Week 24	225.91 percentage change Standard Deviation 130.798
Percentage Change From Baseline in Serum Osteocalcin at Weeks 8, 24 and 52 (EOT) Percentage change at Week 52 (EOT)	294.93 percentage change Standard Deviation 215.100

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 24 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Percentage change from baseline in procollagen 1 N-terminal propeptide at Weeks 8, 24 and 52 (EOT) was reported.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Percentage Change From Baseline in Procollagen 1 N-Terminal Propeptide at Weeks 8, 24 and 52 (EOT) Percentage change at Week 8	119.98 percentage change Standard Deviation 161.156
Percentage Change From Baseline in Procollagen 1 N-Terminal Propeptide at Weeks 8, 24 and 52 (EOT) Percentage change at Week 24	412.46 percentage change Standard Deviation 248.423
Percentage Change From Baseline in Procollagen 1 N-Terminal Propeptide at Weeks 8, 24 and 52 (EOT) Percentage change at Week 52 (EOT)	476.07 percentage change Standard Deviation 377.383

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 24 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Percentage change from baseline in type I collagen C-telopeptides at Week 8, 24 and 52 (EOT) was reported.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Percentage Change From Baseline in Type I Collagen C-Telopeptides at Weeks 8, 24 and 52 (EOT) Percentage change at Week 8	124.62 percentage change Standard Deviation 160.564
Percentage Change From Baseline in Type I Collagen C-Telopeptides at Weeks 8, 24 and 52 (EOT) Percentage change at Week 24	254.26 percentage change Standard Deviation 198.947
Percentage Change From Baseline in Type I Collagen C-Telopeptides at Weeks 8, 24 and 52 (EOT) Percentage change at Week 52 (EOT)	227.13 percentage change Standard Deviation 182.262

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 24 and 52 (EOT)

Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84). Here "number analyzed" were participants who were evaluable for the outcome measure at given time points.

Percentage change from baseline in type I collagen N-telopeptides at Week 8, 24 and 52 (EOT) was reported.

Outcome measures

Measure	rhPTH(1-84) n=22 Participants Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Percentage Change From Baseline in Type I Collagen N-Telopeptides at Weeks 8, 24 and 52 (EOT) Percentage change at Week 24	183.23 percentage change Standard Deviation 160.350
Percentage Change From Baseline in Type I Collagen N-Telopeptides at Weeks 8, 24 and 52 (EOT) Percentage change at Week 52 (EOT)	231.80 percentage change Standard Deviation 270.229
Percentage Change From Baseline in Type I Collagen N-Telopeptides at Weeks 8, 24 and 52 (EOT) Percentage change at Week 8	71.33 percentage change Standard Deviation 99.933

Adverse Events

rhPTH(1-84)

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	rhPTH(1-84) n=22 participants at risk Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Infections and infestations Appendicitis	4.5% 1/22 • Number of events 1 • From start of screening up to end of study (Week 56)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	4.5% 1/22 • Number of events 1 • From start of screening up to end of study (Week 56)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	4.5% 1/22 • Number of events 1 • From start of screening up to end of study (Week 56)
Nervous system disorders Cerebellar haemorrhage	4.5% 1/22 • Number of events 1 • From start of screening up to end of study (Week 56)

Other adverse events

Measure	rhPTH(1-84) n=22 participants at risk Participants received rhPTH(1-84) (Natpara) 50 mcg, injection, subcutaneously, once daily in the thigh (alternate thigh every day) up to 52 weeks (EOT/ET). Dose escalation was done up to 100 mcg in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining ACSC levels in the range of 2-2.25 mmol/L (8-9 mg/dL). Administered dose was maintained once a participant achieved a stable ACSC level of 2-2.25 mmol/L (8-9 mg/dL) and had minimized supplement (active vitamin D and calcium supplement) doses. If ACSC was \>2.25 mmol/L (\>9.0 mg/dL), a starting dose of 25 mcg was administered.
Gastrointestinal disorders Nausea	27.3% 6/22 • Number of events 7 • From start of screening up to end of study (Week 56)
Gastrointestinal disorders Vomiting	9.1% 2/22 • Number of events 4 • From start of screening up to end of study (Week 56)
General disorders Fatigue	18.2% 4/22 • Number of events 5 • From start of screening up to end of study (Week 56)
Infections and infestations Nasopharyngitis	13.6% 3/22 • Number of events 3 • From start of screening up to end of study (Week 56)
Metabolism and nutrition disorders Hypercalcaemia	18.2% 4/22 • Number of events 5 • From start of screening up to end of study (Week 56)
Metabolism and nutrition disorders Hypocalcaemia	9.1% 2/22 • Number of events 4 • From start of screening up to end of study (Week 56)
Musculoskeletal and connective tissue disorders Muscle spasms	13.6% 3/22 • Number of events 6 • From start of screening up to end of study (Week 56)
Musculoskeletal and connective tissue disorders Myalgia	9.1% 2/22 • Number of events 2 • From start of screening up to end of study (Week 56)
Musculoskeletal and connective tissue disorders Osteoarthritis	9.1% 2/22 • Number of events 2 • From start of screening up to end of study (Week 56)
Musculoskeletal and connective tissue disorders Tendonitis	9.1% 2/22 • Number of events 2 • From start of screening up to end of study (Week 56)
Nervous system disorders Headache	13.6% 3/22 • Number of events 7 • From start of screening up to end of study (Week 56)
Nervous system disorders Migraine	9.1% 2/22 • Number of events 3 • From start of screening up to end of study (Week 56)
Nervous system disorders Paraesthesia	9.1% 2/22 • Number of events 2 • From start of screening up to end of study (Week 56)
Psychiatric disorders Anxiety	9.1% 2/22 • Number of events 2 • From start of screening up to end of study (Week 56)

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER