Hypoparathyroidism
Conditions
Brief summary
This study is open to adults with hypoparathyroidism who complete the SHP634-101 study (PARALLAX Study). The purpose of this study is to see if rhPTH(1-84) is safe and effective in adults with hypoparathyroidism who previously participated in the SHP634-101 study. All participants enrolled in this study will receive rhPTH(1-84) once-daily for 52 weeks via an injection. Patients who complete the SHP634-101 study will have the option to screen for this extension study.
Interventions
BIOLOGICALrhPTH(1-84)
Participants will receive rhPTH(1-84) SC injection in the thigh (alternate thigh every day) QD.
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* An understanding, ability, and willingness to fully comply with study procedures and restrictions * Ability to voluntarily provide written, signed, and dated informed consent to participate in the study. * Previously completed the SHP634-101 (NCT02781844) study, including the 30-day follow-up. * Male or non-pregnant, non-lactating female subjects who agree to comply with applicable contraceptive requirements of the protocol or females of non-childbearing potential.
Exclusion criteria
* Received investigational study drug, aside from that received in study SHP634-101 (NCT02781844), within 3 months prior to the screening visit. * Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine (with exception of the condition under study), or neurologic system(s) or psychiatric disease, that in the opinion of the investigator, would make the subject unsuitable for this study. * Received parathyroid hormone (PTH), PTH analog, or parathyroid hormone fragment 1-34 \[PTH(1-34)\] treatment within the last 30 days from the screening visit. * Subjects with a history of parathyroid hormone intolerance, based on investigator determination. * Any disease that might affect calcium metabolism or calcium-phosphate homeostasis as determined by the investigator other than hypoparathyroidism, including but not limited to, active hyperthyroidism; poorly controlled insulin-dependent diabetes mellitus or type 2 diabetes mellitus; severe and chronic cardiac, liver or renal disease; Cushing's syndrome; neuromuscular disease such as rheumatoid arthritis; myeloma; pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy, bone metastases or a history of skeletal malignancies; primary or secondary hyperparathyroidism; a history of parathyroid carcinoma; hypopituitarism, acromegaly; or multiple endocrine neoplasia types 1 and 2 . * Subjects who are at increased baseline risk for osteosarcoma such as subjects with Paget's disease of bone or unexplained elevations of alkaline phosphatase, young adult subjects with open epiphyses, subjects with hereditary disorders predisposing to osteosarcoma or subjects with a prior history of external beam or implant radiation therapy involving the skeleton. * Use of the following medications prior to administration of investigational product within: 1. 30 days-loop diuretics, lithium, systemic corticosteroids (medical judgment is required by the investigator. Primarily high doses of systemic corticosteroids \[example (eg), prednisone\] should be excluded. Stable doses of hydrocortisone \[eg, as treatment for Addison's disease\] may be acceptable). 2. 3 months-cinacalcet hydrochloride 3. 6 months-fluoride tablets, oral bisphosphonates, methotrexate, growth hormone, digoxin 4. 12 months-intravenous bisphosphonates, drug or alcohol abuse, as determined by the investigator * Presence of any clinically significant results from laboratory tests, vital signs assessments, or electrocardiograms (ECG), that in the opinion of the investigator, would make the subject unsuitable for this study. * Any medical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for this study. * History of a clinically significant illness during the 4 weeks prior to dosing, that in the opinion of the investigator, would make the subject unsuitable for this study. * History of any clinically significant surgery or procedure within 8 weeks of first dose, as determined by the investigator or expected to undergo a major surgical procedure during the trial. * History of an allergic response(s) to PTH, PTH analogs, or PTH(1-34), or other clinically significant allergies, that in the opinion of the investigator, would make the subject unsuitable for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | At Week 24 | Percentage of participants who achieved ACSC values \>= to range of 1.875 mmol/L and \<= ULN at Week 24 was reported. |
| 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]) | At Week 52 (EOT) | Percentage of participants who achieved ACSC values \>= to range of 1.875 mmol/L and \<= ULN at Week 52 (EOT) was reported. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | From start of study drug administration to end of study (Week 56) | 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. |
| Number of Participants With Clinically Significant Change in Clinical Laboratory Values | From start of study drug administration to end of study (Week 56) | 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. |
| Number of Participants With Clinically Significant Change in Vital Sign | From start of study drug administration to end of study (Week 56) | 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. |
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters | From start of study drug administration to end of study (Week 56) | 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. |
| Number of Participants With Clinically Significant Change in Estimated Glomerular Filtration Rate (eGFR) Values | From start of study drug administration to end of study (Week 56) | 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. |
| Number of Participants With Clinically Significant Change in Serum Creatinine Value | From start of study drug administration to end of study (Week 56) | 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. |
| Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 24 | Week 24 | Number of participants with positive anti-parathyroid hormone antibodies at Week 24 was reported. |
| Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 52 (EOT) | Week 52 (EOT) | Number of participants with positive anti-parathyroid hormone antibodies at Week 52 (EOT) was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Albumin Corrected Serum Calcium (ACSC) Concentration at Weeks 24 and 52 (EOT) | Baseline, Weeks 24 and 52 (EOT) | Change from baseline in ACSC concentration at Weeks 24 and 52 (EOT) was reported. |
| Percentage Change From Baseline in Type I Collagen N-Telopeptides at Weeks 8, 24 and 52 (EOT) | Baseline, Weeks 8, 24 and 52 (EOT) | Percentage change from baseline in type I collagen N-telopeptides at Week 8, 24 and 52 (EOT) was reported. |
| Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) | Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) | Change from baseline in serum phosphate concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) was reported. |
| Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) | Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) | 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. |
| Change From Baseline in 24-hour Urine Calcium Excretion at Weeks 16, 32 and 52 (EOT) | Baseline, Weeks 16, 32 and 52 (EOT) | Change from baseline in 24-hour urine calcium excretion at Weeks 16, 32 and 52 (EOT) was reported. |
| 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]) | Baseline and at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) | 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. |
| Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) | Baseline, Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) | 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. |
| Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase at Weeks 8, 24 and 52 (EOT) | Baseline, Weeks 8, 24 and 52 (EOT) | Percentage change from baseline in serum bone-specific alkaline phosphatase at Weeks 8, 24 and 52 (EOT) was reported. |
| Percentage Change From Baseline in Serum Osteocalcin at Weeks 8, 24 and 52 (EOT) | Baseline, Weeks 8, 24 and 52 (EOT) | Percentage change from baseline in serum osteocalcin at Weeks 8, 24 and 52 (EOT) was reported. |
| Percentage Change From Baseline in Procollagen 1 N-Terminal Propeptide at Weeks 8, 24 and 52 (EOT) | Baseline, Weeks 8, 24 and 52 (EOT) | Percentage change from baseline in procollagen 1 N-terminal propeptide at Weeks 8, 24 and 52 (EOT) was reported. |
| Percentage Change From Baseline in Type I Collagen C-Telopeptides at Weeks 8, 24 and 52 (EOT) | Baseline, Weeks 8, 24 and 52 (EOT) | Percentage change from baseline in type I collagen C-telopeptides at Week 8, 24 and 52 (EOT) was reported. |
Countries
Canada, Denmark, Hungary, United States
Participant flow
Recruitment details
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).
Pre-assignment details
A total of 22 participants were enrolled and treated in the study, of which 14 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| rhPTH(1-84) 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. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Early termination due to Food and Drug Administration recall of rhPTH(1-84) (Natpara) | 6 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | rhPTH(1-84) |
|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 11.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Native American And Caucasian | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized White | 20 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 10 / 22 |
| serious Total, serious adverse events | 4 / 22 |
Outcome results
Primary
Number of Participants With Clinically Significant Change in Clinical Laboratory Values
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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhPTH(1-84) | Number of Participants With Clinically Significant Change in Clinical Laboratory Values | 0 Participants |
Primary
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters
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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhPTH(1-84) | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters | 0 Participants |
Primary
Number of Participants With Clinically Significant Change in Estimated Glomerular Filtration Rate (eGFR) Values
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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhPTH(1-84) | Number of Participants With Clinically Significant Change in Estimated Glomerular Filtration Rate (eGFR) Values | 0 Participants |
Primary
Number of Participants With Clinically Significant Change in Serum Creatinine Value
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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhPTH(1-84) | Number of Participants With Clinically Significant Change in Serum Creatinine Value | 0 Participants |
Primary
Number of Participants With Clinically Significant Change in Vital Sign
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.
Time frame: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhPTH(1-84) | Number of Participants With Clinically Significant Change in Vital Sign | 0 Participants |
Primary
Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 24
Number of participants with positive anti-parathyroid hormone antibodies at Week 24 was reported.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhPTH(1-84) | Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 24 | 0 Participants |
Primary
Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 52 (EOT)
Number of participants with positive anti-parathyroid hormone antibodies at Week 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhPTH(1-84) | Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 52 (EOT) | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
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.
Time frame: 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).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rhPTH(1-84) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 17 Participants |
| rhPTH(1-84) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with serious TEAEs | 4 Participants |
Primary
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
Percentage of participants who achieved ACSC values \>= to range of 1.875 mmol/L and \<= ULN at Week 24 was reported.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rhPTH(1-84) | 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
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])
Percentage of participants who achieved ACSC values \>= to range of 1.875 mmol/L and \<= ULN at Week 52 (EOT) was reported.
Time frame: At Week 52 (EOT)
Population: Safety analysis population consisted of all participants who had received at least 1 dose of rhPTH(1-84).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rhPTH(1-84) | 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 |
Secondary
Change From Baseline in 24-hour Urine Calcium Excretion at Weeks 16, 32 and 52 (EOT)
Change from baseline in 24-hour urine calcium excretion at Weeks 16, 32 and 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
Secondary
Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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
Change From Baseline in Albumin Corrected Serum Calcium (ACSC) Concentration at Weeks 24 and 52 (EOT)
Change from baseline in ACSC concentration at Weeks 24 and 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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
Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)
Change from baseline in serum phosphate concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 0.259 |
Secondary
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 from baseline in prescribed supplemental oral calcium dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) were reported.
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 43.87 |
Secondary
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 from baseline in prescribed supplemental oral calcium dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) were reported.
Time frame: 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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
Percentage Change From Baseline in Procollagen 1 N-Terminal Propeptide at Weeks 8, 24 and 52 (EOT)
Percentage change from baseline in procollagen 1 N-terminal propeptide at Weeks 8, 24 and 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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
Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase at Weeks 8, 24 and 52 (EOT)
Percentage change from baseline in serum bone-specific alkaline phosphatase at Weeks 8, 24 and 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
Secondary
Percentage Change From Baseline in Serum Osteocalcin at Weeks 8, 24 and 52 (EOT)
Percentage change from baseline in serum osteocalcin at Weeks 8, 24 and 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 215.1 |
Secondary
Percentage Change From Baseline in Type I Collagen C-Telopeptides at Weeks 8, 24 and 52 (EOT)
Percentage change from baseline in type I collagen C-telopeptides at Week 8, 24 and 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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
Percentage Change From Baseline in Type I Collagen N-Telopeptides at Weeks 8, 24 and 52 (EOT)
Percentage change from baseline in type I collagen N-telopeptides at Week 8, 24 and 52 (EOT) was reported.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| rhPTH(1-84) | 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 |
| rhPTH(1-84) | 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 160.35 |
| rhPTH(1-84) | 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 |