Trial Outcomes & Findings for A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism (NCT NCT02910466)
NCT ID: NCT02910466
Last Updated: 2021-07-28
Results Overview
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
39 participants
Primary outcome timeframe
Baseline (402), Month 12
Results posted on
2021-07-28
Participant Flow
The study was conducted at a single site in the United States between 27 October 2016 (first participant first visit) and 20 December 2019 (last participant last visit).
A total of 39 participants were enrolled in the study who were treated in the core AAAE0544 (NCT01199614) study, out of which, 36 participants received treatment in this study. This study reports the additional data only for the current study (SHP634-402) which is on long term safety and efficacy of over 36 months of exposure to rhPTH(1-84), and the results for core study AAAE0544 (NCT01199614) will be posted separately, as planned.
Participant milestones
| Measure |
rhPTH(1-84)
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Overall Study
STARTED
|
39
|
|
Overall Study
Safety Set
|
39
|
|
Overall Study
Treated
|
36
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
39
|
Reasons for withdrawal
| Measure |
rhPTH(1-84)
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Lost to Follow-up
|
5
|
|
Overall Study
Due to Food and Drug Administration (FDA) recall
|
29
|
|
Overall Study
Participant didn't meet inclusion criteria
|
1
|
Baseline Characteristics
A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism
Baseline characteristics by cohort
| Measure |
rhPTH(1-84)
n=39 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Age, Continuous
|
51.9 Years
STANDARD_DEVIATION 12.22 • n=5 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
38 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (402), Month 6Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Outcome measures
| Measure |
rhPTH(1-84)
n=23 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 6
|
-0.005 Millimole per liter (mmol/L)
Standard Deviation 0.1546
|
PRIMARY outcome
Timeframe: Baseline (402), Month 12Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Outcome measures
| Measure |
rhPTH(1-84)
n=29 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 12
|
0.069 mmol/L
Standard Deviation 0.1838
|
PRIMARY outcome
Timeframe: Baseline (402), Month 18Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Outcome measures
| Measure |
rhPTH(1-84)
n=30 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 18
|
0.066 mmol/L
Standard Deviation 0.2158
|
PRIMARY outcome
Timeframe: Baseline (402), Month 24Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Outcome measures
| Measure |
rhPTH(1-84)
n=27 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 24
|
0.112 mmol/L
Standard Deviation 0.2314
|
PRIMARY outcome
Timeframe: Baseline (402), Month 30Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Outcome measures
| Measure |
rhPTH(1-84)
n=21 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 30
|
0.145 mmol/L
Standard Deviation 0.2447
|
PRIMARY outcome
Timeframe: Baseline (402), Month 36Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure.
Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Outcome measures
| Measure |
rhPTH(1-84)
n=1 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 36
|
0.170 mmol/L
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
PRIMARY outcome
Timeframe: Baseline (402), EOT (up to Month 36)Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=33 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at End of Treatment (EOT) (up to Month 36)
|
0.135 mmol/L
Standard Deviation 0.2260
|
SECONDARY outcome
Timeframe: At Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Albumin-corrected Serum Calcium (mmol/L) = Total Calcium (mmol/L) + 0.02 \* (40 gram per liter \[g/L\] - Albumin \[g/L\]).
Outcome measures
| Measure |
rhPTH(1-84)
n=36 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 6: less than (<) 1.875 mmol/L
|
20.8 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 6: 1.875 mmol/L to ULN
|
79.2 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 6: >ULN
|
0 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 12: <1.875 mmol/L
|
31.3 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 12: 1.875 mmol/L to ULN
|
65.6 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 12: > ULN
|
3.1 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 18: <1.875 mmol/L
|
24.2 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 18: 1.875 mmol/L to ULN
|
75.8 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 18: >ULN
|
0 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 24: <1.875 mmol/L
|
16.7 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 24: 1.875 mmol/L to ULN
|
83.3 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 24: >ULN
|
0 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 30: <1.875 mmol/L
|
17.4 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 30: 1.875 mmol/L to ULN
|
78.3 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 30: >ULN
|
4.3 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 36: <1.875 mmol/L
|
0 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 36: 1.875 mmol/L to ULN
|
100 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At Month 36: >ULN
|
0 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At EOT (up to Month 36): <1.875 mmol/L
|
13.9 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At EOT (up to Month 36): 1.875 mmol/L to ULN
|
83.3 Percentage of participants
|
|
Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
At EOT (up to Month 36): >ULN
|
2.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Outcome measures
| Measure |
rhPTH(1-84)
n=34 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 6
|
-0.403 Millimole per day (mmol/day)
Standard Deviation 2.7785
|
|
Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 12
|
0.442 Millimole per day (mmol/day)
Standard Deviation 2.7419
|
|
Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 18
|
0.946 Millimole per day (mmol/day)
Standard Deviation 3.2615
|
|
Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 24
|
1.378 Millimole per day (mmol/day)
Standard Deviation 3.1076
|
|
Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 30
|
2.163 Millimole per day (mmol/day)
Standard Deviation 4.2794
|
|
Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at EOT (up to Month 36)
|
1.213 Millimole per day (mmol/day)
Standard Deviation 3.3632
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=33 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 18
|
0.070 mmol/L
Standard Deviation 0.3213
|
|
Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 24
|
0.074 mmol/L
Standard Deviation 0.2825
|
|
Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 6
|
0.041 mmol/L
Standard Deviation 0.2282
|
|
Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 12
|
0.077 mmol/L
Standard Deviation 0.2925
|
|
Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 30
|
0.012 mmol/L
Standard Deviation 0.2992
|
|
Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 36
|
-0.040 mmol/L
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at EOT (up to Month 36)
|
0.055 mmol/L
Standard Deviation 0.2861
|
SECONDARY outcome
Timeframe: Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=36 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Prescribed Data: Change at Month 6
|
52.1 milligram per day (mg/day)
Standard Deviation 547.62
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Prescribed Data: Change at Month 12
|
-125.6 milligram per day (mg/day)
Standard Deviation 1189.52
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Prescribed Data: Change at Month 18
|
-150.9 milligram per day (mg/day)
Standard Deviation 1140.42
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Prescribed Data: Change at Month 24
|
-146.0 milligram per day (mg/day)
Standard Deviation 1401.84
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Prescribed Data: Change at Month 30
|
-105.7 milligram per day (mg/day)
Standard Deviation 1262.95
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Prescribed Data: Change at Month 36
|
230.0 milligram per day (mg/day)
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Prescribed Data: Change at EOT (up to Month 36)
|
-237.8 milligram per day (mg/day)
Standard Deviation 1208.06
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Prescribed Data: Change at Month 6
|
-71.35 milligram per day (mg/day)
Standard Deviation 360.730
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Prescribed Data: Change at Month 12
|
-201.62 milligram per day (mg/day)
Standard Deviation 719.878
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Prescribed Data: Change at Month 18
|
-206.40 milligram per day (mg/day)
Standard Deviation 727.017
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Prescribed Data: Change at Month 24
|
-239.71 milligram per day (mg/day)
Standard Deviation 898.529
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Prescribed Data: Change at Month 30
|
-175.56 milligram per day (mg/day)
Standard Deviation 861.198
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Prescribed Data: Change at Month 36
|
-267.70 milligram per day (mg/day)
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Prescribed Data: Change at EOT (up to Month 36)
|
-224.31 milligram per day (mg/day)
Standard Deviation 766.956
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Diary Data: Change at Month 6
|
537.420 milligram per day (mg/day)
Standard Deviation 679.5444
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Diary Data: Change at Month 12
|
549.757 milligram per day (mg/day)
Standard Deviation 974.4770
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Diary Data: Change at Month 18
|
1241.382 milligram per day (mg/day)
Standard Deviation 3353.7093
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Diary Data: Change at Month 24
|
375.005 milligram per day (mg/day)
Standard Deviation 797.0665
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Diary Data: Change at Month 30
|
102.174 milligram per day (mg/day)
Standard Deviation 240.7955
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Diary Data: Change at Month 36
|
0.000 milligram per day (mg/day)
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Calcium Diary Data: Change at EOT (up to Month 36)
|
75.545 milligram per day (mg/day)
Standard Deviation 220.3270
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Diary Data: Change at Month 6
|
151.528 milligram per day (mg/day)
Standard Deviation 197.2856
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Diary Data: Change at Month 12
|
194.332 milligram per day (mg/day)
Standard Deviation 414.3470
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Diary Data: Change at Month 18
|
418.160 milligram per day (mg/day)
Standard Deviation 1334.7574
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Diary Data: Change at Month 24
|
145.618 milligram per day (mg/day)
Standard Deviation 348.2148
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Diary Data: Change at Month 30
|
28.854 milligram per day (mg/day)
Standard Deviation 67.2635
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Diary Data: Change at Month 36
|
0.000 milligram per day (mg/day)
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Elemental Calcium Diary Data: Change at EOT (up to Month 36)
|
25.868 milligram per day (mg/day)
Standard Deviation 80.6473
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=36 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Prescribed Data: Change at Month 6
|
-0.012 microgram per day (mcg/day)
Standard Deviation 0.0514
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Prescribed Data: Change at Month 12
|
-0.056 microgram per day (mcg/day)
Standard Deviation 0.2747
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Prescribed Data: Change at Month 18
|
-0.062 microgram per day (mcg/day)
Standard Deviation 0.3125
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Prescribed Data: Change at Month 24
|
-0.092 microgram per day (mcg/day)
Standard Deviation 0.3565
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Prescribed Data: Change at Month 30
|
-0.034 microgram per day (mcg/day)
Standard Deviation 0.3559
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Prescribed Data: Change at Month 36
|
0.000 microgram per day (mcg/day)
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Prescribed Data: Change at EOT (up to Month 36)
|
-0.063 microgram per day (mcg/day)
Standard Deviation 0.4022
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Diary Data: Change at Month 6
|
0.063 microgram per day (mcg/day)
Standard Deviation 0.2117
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Diary Data: Change at Month 12
|
0.032 microgram per day (mcg/day)
Standard Deviation 0.1109
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Diary Data: Change at Month 18
|
0.015 microgram per day (mcg/day)
Standard Deviation 0.0606
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Diary Data: Change at Month 24
|
0.092 microgram per day (mcg/day)
Standard Deviation 0.3742
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Diary Data: Change at Month 30
|
0.000 microgram per day (mcg/day)
Standard Deviation 0.0000
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Diary Data: Change at Month 36
|
0.000 microgram per day (mcg/day)
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Diary Data: Change at EOT (up to Month 36)
|
0.000 microgram per day (mcg/day)
Standard Deviation 0.0000
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
The HPT-SD was a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness and depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None (0), Mild (1), Moderate (2), Severe (3), Very severe (4) and for items 10-13, it ranges from Not at all (0), somewhat (1), Very much (2). For symptom subscale score was calculated as average score of the items 1-7 and the impact subscale scores was calculated as average score of the items 10-13. The HPT-SD was only collected within the SHP634-402 study, as planned.
Outcome measures
| Measure |
rhPTH(1-84)
n=33 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sadness and Depression: Change at Month 6
|
0.3 Score on a Scale
Standard Deviation 0.65
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sadness and Depression: Change at Month 12
|
-0.1 Score on a Scale
Standard Deviation 0.58
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Symptom Subscale: Change at Month 6
|
0.06 Score on a Scale
Standard Deviation 0.680
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Symptom Subscale: Change at Month 12
|
-0.31 Score on a Scale
Standard Deviation 0.762
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Symptom Subscale: Change at Month 18
|
-0.27 Score on a Scale
Standard Deviation 0.831
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Symptom Subscale: Change at Month 24
|
-0.25 Score on a Scale
Standard Deviation 0.544
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Symptom Subscale: Change at Month 30
|
-0.20 Score on a Scale
Standard Deviation 0.737
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Symptom Subscale: Change at Month 36
|
0.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Symptom Subscale: Change at EOT (up to Month 36)
|
-0.15 Score on a Scale
Standard Deviation 0.867
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety: Change at Month 6
|
0.1 Score on a Scale
Standard Deviation 0.64
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety: Change at Month 12
|
0.1 Score on a Scale
Standard Deviation 0.74
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety: Change at Month 18
|
0.0 Score on a Scale
Standard Deviation 0.68
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety: Change at Month 24
|
0.1 Score on a Scale
Standard Deviation 0.75
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety: Change at Month 30
|
0.2 Score on a Scale
Standard Deviation 0.74
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety: Change at Month 36
|
0.0 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety: Change at EOT (up to Month 36)
|
0.3 Score on a Scale
Standard Deviation 0.80
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sadness and Depression: Change at Month 18
|
0.0 Score on a Scale
Standard Deviation 0.66
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sadness and Depression: Change at Month 24
|
0.3 Score on a Scale
Standard Deviation 0.72
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sadness and Depression: Change at Month 30
|
0.2 Score on a Scale
Standard Deviation 0.95
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sadness and Depression: Change at Month 36
|
0.0 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sadness and Depression: Change at EOT (up to Month 36)
|
0.2 Score on a Scale
Standard Deviation 0.95
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Impact Subscale: Change at Month 6
|
-0.05 Score on a Scale
Standard Deviation 0.391
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Impact Subscale: Change at Month 12
|
-0.13 Score on a Scale
Standard Deviation 0.400
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Impact Subscale: Change at Month 18
|
-0.10 Score on a Scale
Standard Deviation 0.363
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Impact Subscale: Change at Month 24
|
-0.01 Score on a Scale
Standard Deviation 0.335
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Impact Subscale: Change at Month 30
|
-0.10 Score on a Scale
Standard Deviation 0.413
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Impact Subscale: Change at Month 36
|
0.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Impact Subscale: Change at EOT (up to Month 36)
|
-0.07 Score on a Scale
Standard Deviation 0.377
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
FACT-Cog assessment was a 37-item tool with each item rated on a 5-point scale ranging from 0 to 4. It included 4 subscales: perceived cognitive impairments (CogPCI) (20 items, Item 1 - 20, score range 0-80), impact of perceived cognitive impairments on quality of life (CogQOL ) (4 items, Item 34 - 37, score range 0-16), comments from others (CogOth) (4 items, Item 21 - 24, score range 0-16) and perceived cognitive ability (CogPCA) (9 items, Item 25 - 33 score range 0-36). CogPCI subscale and comments from others subscale and two others subscale ranged as following: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much). For all four subscales of the FACT-cog: higher scores reflect worse cognitive function. Baseline (402): the last available pre-dose value in SHP634-402. EOT: the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=36 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCI: Change at Month 12
|
1.0 Score on a Scale
Standard Deviation 9.28
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCI: Change at Month 6
|
0.0 Score on a Scale
Standard Deviation 6.88
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCI: Change at Month 18
|
-1.4 Score on a Scale
Standard Deviation 9.44
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCI: Change at Month 24
|
-0.5 Score on a Scale
Standard Deviation 9.35
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCI: Change at Month 30
|
-0.3 Score on a Scale
Standard Deviation 10.87
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCI: Change at Month 36
|
-1.0 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCI: Change at EOT (up to Month 36)
|
-0.4 Score on a Scale
Standard Deviation 11.14
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogQOL: Change at Month 6
|
-0.1 Score on a Scale
Standard Deviation 2.27
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogQOL: Change at Month 12
|
1.5 Score on a Scale
Standard Deviation 2.92
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogQOL: Change at Month 18
|
0.2 Score on a Scale
Standard Deviation 3.16
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogQOL: Change at Month 24
|
1.5 Score on a Scale
Standard Deviation 3.63
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogQOL: Change at Month 30
|
0.6 Score on a Scale
Standard Deviation 3.20
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogQOL: Change at Month 36
|
0.0 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogQOL: Change at EOT (up to Month 36)
|
0.7 Score on a Scale
Standard Deviation 3.20
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogOth: Change at Month 6
|
0.0 Score on a Scale
Standard Deviation 2.10
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogOth: Change at Month 12
|
0.4 Score on a Scale
Standard Deviation 1.85
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogOth: Change at Month 18
|
0.7 Score on a Scale
Standard Deviation 2.46
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogOth: Change at Month 24
|
-0.2 Score on a Scale
Standard Deviation 1.89
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogOth: Change at Month 30
|
-0.2 Score on a Scale
Standard Deviation 2.79
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogOth: Change at Month 36
|
0.0 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogOth: Change at EOT (up to Month 36)
|
0.2 Score on a Scale
Standard Deviation 2.79
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCA: Change at Month 6
|
-0.2 Score on a Scale
Standard Deviation 2.60
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCA: Change at Month 12
|
-1.1 Score on a Scale
Standard Deviation 5.59
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCA: Change at Month 18
|
-0.1 Score on a Scale
Standard Deviation 5.12
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCA: Change at Month 24
|
0.0 Score on a Scale
Standard Deviation 4.41
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCA: Change at Month 30
|
0.2 Score on a Scale
Standard Deviation 6.62
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCA: Change at Month 36
|
-2.0 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
CogPCA: Change at EOT (up to Month 36)
|
0.3 Score on a Scale
Standard Deviation 4.68
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
FACIT fatigue questionnaire contains 13 fatigue-related questions. The responses to the 13 items on the FACIT fatigue questionnaire was measured on a 4-point Likert scale (0-4). Thus, the total score ranges from 0 to 52. High scores represent less fatigue and better quality of life. For 2 questions, item 7 'I have energy' and item 8 'I am able to do my usual activities', the item response from questionnaire will be used as item score and no conversion is needed. For the rest of 11 questions, item score was calculated as 4- item response. Fatigue total score was calculated as: Fatigue Total Score = \[sum of (item scores)\]\*13/ (number of items answered). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=36 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 6
|
-1.41 Score on a Scale
Standard Deviation 4.932
|
|
Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 12
|
0.10 Score on a Scale
Standard Deviation 7.357
|
|
Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 18
|
-0.02 Score on a Scale
Standard Deviation 7.467
|
|
Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 24
|
-0.13 Score on a Scale
Standard Deviation 8.618
|
|
Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 30
|
-1.92 Score on a Scale
Standard Deviation 10.777
|
|
Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at Month 36
|
-1.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Change at EOT (up to Month 36)
|
-1.01 Score on a Scale
Standard Deviation 8.171
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
The HADS was a 14-item scale that generates ordinal data. Seven of the items related to anxiety (Item 1, 3, 5, 7, 9, 11 and 13) and seven related to depression (Item 2, 4, 6, 8, 10, 12 and 14). The scale was designed to avoid reliance on aspects of conditions that are also common somatic symptoms of illness. Each item on the questionnaire was scored from 0-3, therefore, a person can score between 0 and 21 for either anxiety or depression. For each of the two sub-scores, if a participant obtain a score ranged from: 0 to 7, he is considered as "normal"; 8-10 = Borderline abnormal (borderline case) and 11-21 = Abnormal (case). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=36 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety Subscale: Change at Month 6
|
0.6 Score on a Scale
Standard Deviation 2.39
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety Subscale: Change at Month 12
|
-0.5 Score on a Scale
Standard Deviation 2.96
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety Subscale: Change at Month 18
|
-0.2 Score on a Scale
Standard Deviation 3.74
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety Subscale: Change at Month 24
|
-1.5 Score on a Scale
Standard Deviation 3.26
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety Subscale: Change at Month 30
|
-0.4 Score on a Scale
Standard Deviation 3.21
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety Subscale: Change at Month 36
|
2.0 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Anxiety Subscale: Change at EOT (up to Month 36)
|
-0.4 Score on a Scale
Standard Deviation 3.18
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Depression Subscale: Change at Month 6
|
0.4 Score on a Scale
Standard Deviation 2.67
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Depression Subscale: Change at Month 12
|
-0.6 Score on a Scale
Standard Deviation 2.61
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Depression Subscale: Change at Month 18
|
-0.8 Score on a Scale
Standard Deviation 2.86
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Depression Subscale: Change at Month 24
|
-0.4 Score on a Scale
Standard Deviation 3.84
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Depression Subscale: Change at Month 30
|
-1.0 Score on a Scale
Standard Deviation 3.58
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Depression Subscale: Change at Month 36
|
1.0 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Depression Subscale: Change at EOT (up to Month 36)
|
-0.8 Score on a Scale
Standard Deviation 3.35
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 12, 24, 36, and EOT (up to Month 36)Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
SF-36 was a validated questionnaire that questions participants about perceived physical and mental health and function. SF-36 consisted of 8 scaled scores, which were weighted sums of the questions in their section. Each scale was directly transformed into 0-100 scale on the assumption that each question carries equal weight; A score of zero was equivalent to maximum disability and a score of 100 was equivalent to no disability. Eight sections included in SF-36 assessment: vitality (1=none of the time to 5=all of the time), physical functioning (1=yes, limited a lot to 3=no, not limited at all), bodily pain (1=very severe to 6=none), general health (1=poor to 5=excellent), physical role (1=all of the time to 5=none of the time), emotional role (1=all of the time to 5=none of the time), social role (1=all of the time: to 5=none of the time) and mental health (1=all of the time to 5=none of the time). Baseline (402) was defined as the last available pre-dose value in SHP634-402.
Outcome measures
| Measure |
rhPTH(1-84)
n=33 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Vitality: Change at Month 12
|
-0.11 Score on a Scale
Standard Deviation 13.485
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Vitality: Change at Month 24
|
-3.27 Score on a Scale
Standard Deviation 17.641
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Vitality: Change at Month 36
|
-5.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Vitality: Change at EOT (up to Month 36)
|
0.26 Score on a Scale
Standard Deviation 18.006
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Physical functioning: Change at Month 12
|
1.61 Score on a Scale
Standard Deviation 14.340
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Physical functioning: Change at Month 24
|
0.00 Score on a Scale
Standard Deviation 13.676
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Physical functioning: Change at Month 36
|
0.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Physical functioning: Change at EOT (up to Month 36)
|
2.66 Score on a Scale
Standard Deviation 20.398
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Bodily pain: Change at Month 12
|
6.55 Score on a Scale
Standard Deviation 16.287
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Bodily pain: Change at Month 24
|
3.54 Score on a Scale
Standard Deviation 13.948
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Bodily pain: Change at Month 36
|
0.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Bodily pain: Change at EOT (up to Month 36)
|
2.44 Score on a Scale
Standard Deviation 15.546
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
General health: Change at Month 12
|
3.28 Score on a Scale
Standard Deviation 12.718
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
General health: Change at Month 24
|
0.31 Score on a Scale
Standard Deviation 13.033
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
General health: Change at Month 36
|
0.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
General health: Change at EOT (up to Month 36)
|
0.24 Score on a Scale
Standard Deviation 11.755
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Physical role: Change at Month 12
|
-1.61 Score on a Scale
Standard Deviation 29.535
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Physical role: Change at Month 24
|
-6.25 Score on a Scale
Standard Deviation 31.641
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Physical role: Change at Month 36
|
0.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Physical role: Change at EOT (up to Month 36)
|
-5.47 Score on a Scale
Standard Deviation 32.213
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Emotional role: Change at Month 12
|
-3.23 Score on a Scale
Standard Deviation 31.453
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Emotional role: Change at Month 24
|
-2.38 Score on a Scale
Standard Deviation 40.500
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Emotional role: Change at Month 36
|
0.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Emotional role: Change at EOT (up to Month 36)
|
-4.17 Score on a Scale
Standard Deviation 45.398
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Social role: Change at Month 12
|
-3.23 Score on a Scale
Standard Deviation 12.487
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Social role: Change at Month 24
|
-1.79 Score on a Scale
Standard Deviation 19.159
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Social role: Change at Month 36
|
0.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Social role: Change at EOT (up to Month 36)
|
-1.17 Score on a Scale
Standard Deviation 19.145
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Mental health: Change at Month 12
|
-0.26 Score on a Scale
Standard Deviation 7.585
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Mental health: Change at Month 24
|
1.43 Score on a Scale
Standard Deviation 12.845
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Mental health: Change at Month 36
|
4.00 Score on a Scale
Standard Deviation NA
Standard deviation could not be calculated because single participant was analyzed.
|
|
Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
Mental health: Change at EOT (up to Month 36)
|
0.50 Score on a Scale
Standard Deviation 12.801
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Change from baseline in concentration of bone turnover markers included; Serum carboxy-terminal 4 telopeptide of type I collagen \[s-CTX\], procollagen type I amino-terminal propeptide \[P1NP\], osteocalcin, and sclerostin. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Outcome measures
| Measure |
rhPTH(1-84)
n=15 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
s-CTX: Change at Month 30
|
-0.204 mcg/L
Standard Deviation 0.2896
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
s-CTX: Change at Month 6
|
-0.082 mcg/L
Standard Deviation 0.1053
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
s-CTX: Change at Month 12
|
-0.190 mcg/L
Standard Deviation 0.9847
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
s-CTX: Change at Month 18
|
0.036 mcg/L
Standard Deviation 0.3030
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
s-CTX: Change at Month 24
|
0.201 mcg/L
Standard Deviation 0.3985
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
s-CTX: Change at EOT (up to Month 36)
|
-0.136 mcg/L
Standard Deviation 0.5429
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
P1NP: Change at Month 6
|
-3.12 mcg/L
Standard Deviation 30.262
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
P1NP: Change at Month 12
|
33.94 mcg/L
Standard Deviation 55.080
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
P1NP: Change at Month 18
|
31.06 mcg/L
Standard Deviation 137.665
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
P1NP: Change at Month 24
|
37.09 mcg/L
Standard Deviation 152.162
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
P1NP: Change at Month 30
|
30.95 mcg/L
Standard Deviation 85.345
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
P1NP: Change at EOT (up to Month 36)
|
80.90 mcg/L
Standard Deviation 175.466
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Osteocalcin: Change at Month 6
|
-4.020 mcg/L
Standard Deviation 11.6418
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Osteocalcin: Change at Month 12
|
-1.199 mcg/L
Standard Deviation 44.2510
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Osteocalcin: Change at Month 18
|
-0.310 mcg/L
Standard Deviation 43.7374
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Osteocalcin: Change at Month 24
|
23.483 mcg/L
Standard Deviation 31.7005
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Osteocalcin: Change at Month 30
|
3.674 mcg/L
Standard Deviation 36.8616
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Osteocalcin: Change at EOT (up to Month 36)
|
29.232 mcg/L
Standard Deviation 65.9276
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sclerostin: Change at Month 6
|
0.013 mcg/L
Standard Deviation 0.1678
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sclerostin: Change at Month 12
|
0.071 mcg/L
Standard Deviation 0.1657
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sclerostin: Change at Month 18
|
0.097 mcg/L
Standard Deviation 0.2512
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sclerostin: Change at Month 24
|
0.092 mcg/L
Standard Deviation 0.1978
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sclerostin: Change at Month 30
|
0.029 mcg/L
Standard Deviation 0.1302
|
|
Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Sclerostin: Change at EOT (up to Month 36)
|
0.075 mcg/L
Standard Deviation 0.1651
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Change from baseline in concentration of bone turnover markers included, bone specific alkaline phosphatase \[BSAP\] and tartrate-resistant acid phosphatase-5b (TRAP-5b). Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Outcome measures
| Measure |
rhPTH(1-84)
n=15 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
BSAP: Change at Month 6
|
-1.194 Units per liter (U/L)
Standard Deviation 4.8791
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
BSAP: Change at Month 12
|
4.310 Units per liter (U/L)
Standard Deviation 11.8965
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
BSAP: Change at Month 18
|
4.824 Units per liter (U/L)
Standard Deviation 13.0980
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
BSAP: Change at Month 24
|
11.546 Units per liter (U/L)
Standard Deviation 14.1455
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
BSAP: Change at Month 30
|
2.124 Units per liter (U/L)
Standard Deviation 9.6951
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
BSAP: Change at EOT (up to Month 36)
|
7.167 Units per liter (U/L)
Standard Deviation 12.4372
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
TRAP-5b: Change at Month 6
|
-0.236 Units per liter (U/L)
Standard Deviation 0.7336
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
TRAP-5b: Change at Month 12
|
0.946 Units per liter (U/L)
Standard Deviation 1.8702
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
TRAP-5b: Change at Month 18
|
1.798 Units per liter (U/L)
Standard Deviation 4.3422
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
TRAP-5b: Change at Month 24
|
2.347 Units per liter (U/L)
Standard Deviation 2.3850
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
TRAP-5b: Change at Month 30
|
1.254 Units per liter (U/L)
Standard Deviation 4.2890
|
|
Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
TRAP-5b: Change at EOT (up to Month 36)
|
1.336 Units per liter (U/L)
Standard Deviation 3.2241
|
SECONDARY outcome
Timeframe: Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Change from baseline in bone architecture was assessed by using DXA. The DXA scans was evaluated for BMD of the lumbar spine (vertebra L1, L2, L3, L4), total hip and femoral neck, and distal radius. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Outcome measures
| Measure |
rhPTH(1-84)
n=24 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L2: Change at Month 30
|
-0.012 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0560
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L2: Change at EOT (up to Month 36)
|
-0.018 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0487
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L3: Change at Month 6
|
-0.018 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0325
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L3: Change at Month 12
|
-0.015 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0466
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L3: Change at Month 18
|
-0.012 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0538
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 6
|
-0.027 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0386
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 12
|
-0.020 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0398
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 18
|
-0.012 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0385
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 24
|
-0.008 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0545
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 30
|
-0.021 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0549
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at EOT (up to Month 36)
|
-0.024 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0524
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L1: Change at Month 6
|
0.000 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0334
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L1: Change at Month 12
|
0.001 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0374
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L1: Change at Month 18
|
0.003 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0426
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L1: Change at Month 24
|
0.018 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0552
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L1: Change at Month 30
|
-0.006 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0656
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L1: Change at EOT (up to Month 36)
|
0.005 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0641
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L2: Change at Month 6
|
-0.020 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0276
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L2: Change at Month 12
|
-0.017 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0399
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L2: Change at Month 18
|
-0.006 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0428
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L2: Change at Month 24
|
-0.001 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0518
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L3: Change at Month 24
|
-0.001 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0495
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L3: Change at Month 30
|
-0.013 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0478
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L3: Change at EOT (up to Month 36)
|
-0.016 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0541
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L4: Change at Month 6
|
-0.015 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0328
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L4: Change at Month 12
|
-0.010 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0362
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L4: Change at Month 18
|
-0.013 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0319
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L4: Change at Month 24
|
-0.004 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0546
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L4: Change at Month 30
|
-0.014 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0513
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar L4: Change at EOT (up to Month 36)
|
-0.023 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0497
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 6
|
-0.010 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0468
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 12
|
-0.027 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0470
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 18
|
-0.025 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0543
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 24
|
-0.032 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0574
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 30
|
-0.020 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0483
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at EOT (up to Month 36)
|
-0.018 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0467
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 6
|
-0.005 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0213
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 12
|
-0.004 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0224
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 18
|
-0.001 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0293
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 24
|
-0.008 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0299
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 30
|
-0.003 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0359
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at EOT (up to Month 36)
|
-0.013 Grams per square centimeter (g/cm^2)
Standard Deviation 0.0358
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal Radius: Change at Month 6
|
0.032 Grams per square centimeter (g/cm^2)
Standard Deviation 0.1204
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal Radius: Change at Month 12
|
0.018 Grams per square centimeter (g/cm^2)
Standard Deviation 0.1104
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal Radius: Change at Month 18
|
0.020 Grams per square centimeter (g/cm^2)
Standard Deviation 0.1193
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal Radius: Change at Month 24
|
0.024 Grams per square centimeter (g/cm^2)
Standard Deviation 0.1278
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal Radius: Change at Month 30
|
0.024 Grams per square centimeter (g/cm^2)
Standard Deviation 0.1276
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal Radius: Change at EOT (up to Month 36)
|
0.011 Grams per square centimeter (g/cm^2)
Standard Deviation 0.1049
|
SECONDARY outcome
Timeframe: Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Change from baseline in bone architecture was assessed by using DXA. The DXA scans was evaluated for Total T-score of the lumbar spine (vertebra L1-L4), hip (total and femoral neck), and ⅓ distal radius. Baseline (402) was defined as the last available pre-dose value in SHP634-402. The T-score was a comparison of a person's bone density with that of a healthy 30-year-old adult of the same sex and ethnicity. T-score included: Normal: \>= -1; Osteopenia: \< -1 and \> -2.5; Osteoporosis: \<= -2.5. A lower T-score implies a lower bone mineral density. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Outcome measures
| Measure |
rhPTH(1-84)
n=24 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 6
|
-0.16 T-score
Standard Deviation 0.343
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 12
|
-0.12 T-score
Standard Deviation 0.331
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 18
|
-0.09 T-score
Standard Deviation 0.338
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 24
|
-0.04 T-score
Standard Deviation 0.477
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at Month 30
|
-0.16 T-score
Standard Deviation 0.506
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine Total: Change at EOT (up to Month 36)
|
-0.18 T-score
Standard Deviation 0.476
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L1: Change at Month 6
|
-0.01 T-score
Standard Deviation 0.293
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L1: Change at Month 12
|
0.01 T-score
Standard Deviation 0.346
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L1: Change at Month 18
|
0.01 T-score
Standard Deviation 0.394
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L1: Change at Month 24
|
0.16 T-score
Standard Deviation 0.508
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L1: Change at Month 30
|
-0.05 T-score
Standard Deviation 0.598
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L1: Change at Month EOT (up to Month 36)
|
0.04 T-score
Standard Deviation 0.588
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L2: Change at Month 6
|
-0.17 T-score
Standard Deviation 0.243
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L2: Change at Month 12
|
-0.15 T-score
Standard Deviation 0.361
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L2: Change at Month 18
|
-0.05 T-score
Standard Deviation 0.394
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L2: Change at Month 24
|
0.01 T-score
Standard Deviation 0.477
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L2: Change at Month 30
|
-0.10 T-score
Standard Deviation 0.512
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L2: Change at EOT (up to Month 36)
|
-0.15 T-score
Standard Deviation 0.440
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L3: Change at Month 6
|
-0.16 T-score
Standard Deviation 0.304
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L3: Change at Month 12
|
-0.12 T-score
Standard Deviation 0.424
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L3: Change at Month 18
|
-0.10 T-score
Standard Deviation 0.518
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L3: Change at Month 24
|
0.03 T-score
Standard Deviation 0.468
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L3: Change at Month 30
|
-0.11 T-score
Standard Deviation 0.461
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L3: Change at EOT (up to Month 36)
|
-0.14 T-score
Standard Deviation 0.509
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L4: Change at Month 6
|
-0.13 T-score
Standard Deviation 0.287
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L4: Change at Month 12
|
-0.09 T-score
Standard Deviation 0.336
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L4: Change at Month 18
|
-0.12 T-score
Standard Deviation 0.306
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L4: Change at Month 24
|
-0.04 T-score
Standard Deviation 0.484
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L4: Change at Month 30
|
-0.14 T-score
Standard Deviation 0.479
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Lumbar Spine L4: Change at EOT (up to Month 36)
|
-0.21 T-score
Standard Deviation 0.456
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 6
|
-0.06 T-score
Standard Deviation 0.386
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 12
|
-0.21 T-score
Standard Deviation 0.390
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 18
|
-0.21 T-score
Standard Deviation 0.448
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 24
|
-0.26 T-score
Standard Deviation 0.462
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at Month 30
|
-0.17 T-score
Standard Deviation 0.451
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Femoral Neck: Change at EOT (up to Month 36)
|
-0.16 T-score
Standard Deviation 0.427
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 6
|
-0.02 T-score
Standard Deviation 0.194
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 12
|
-0.03 T-score
Standard Deviation 0.200
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 18
|
0.00 T-score
Standard Deviation 0.240
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 24
|
-0.07 T-score
Standard Deviation 0.274
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at Month 30
|
-0.02 T-score
Standard Deviation 0.306
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Hip: Change at EOT (up to Month 36)
|
-0.10 T-score
Standard Deviation 0.304
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal 1/3 Radius: Change at Month 6
|
0.00 T-score
Standard Deviation 0.408
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal 1/3 Radius: Change at Month 12
|
-0.09 T-score
Standard Deviation 0.332
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal 1/3 Radius: Change at Month 18
|
-0.07 T-score
Standard Deviation 0.385
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal 1/3 Radius: Change at Month 24
|
-0.11 T-score
Standard Deviation 0.342
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal 1/3 Radius: Change at Month 30
|
-0.16 T-score
Standard Deviation 0.462
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Distal 1/3 Radius: Change at EOT (up to Month 36)
|
-0.22 T-score
Standard Deviation 0.359
|
SECONDARY outcome
Timeframe: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)Population: Safety population: all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Change from baseline in bone architecture was assessed by using HRpQCT. The HRpQCT analyses included both radius and tibia of total area position. Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, '0' in the number analyzed field signifies that no participants were evaluable at specified time point.
Outcome measures
| Measure |
rhPTH(1-84)
n=28 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Tibia, Change at Month 24
|
-6.71 Millimeter square (mm^2)
Standard Deviation 17.861
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Radius, Change at Month 6
|
-2.99 Millimeter square (mm^2)
Standard Deviation 12.143
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Radius, Change at Month 12
|
-1.36 Millimeter square (mm^2)
Standard Deviation 9.358
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Radius, Change at Month 18
|
-3.59 Millimeter square (mm^2)
Standard Deviation 12.111
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Radius, Change at Month 24
|
-5.31 Millimeter square (mm^2)
Standard Deviation 13.761
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Radius, Change at Month 30
|
-6.64 Millimeter square (mm^2)
Standard Deviation 15.009
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Radius, Change at EOT (up to Month 36)
|
-2.21 Millimeter square (mm^2)
Standard Deviation 13.908
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Tibia, Change at Month 6
|
-5.34 Millimeter square (mm^2)
Standard Deviation 20.594
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Tibia, Change at Month 12
|
-2.10 Millimeter square (mm^2)
Standard Deviation 2.941
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Tibia, Change at Month 18
|
-6.02 Millimeter square (mm^2)
Standard Deviation 16.858
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Tibia, Change at Month 30
|
-0.93 Millimeter square (mm^2)
Standard Deviation 6.703
|
|
Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
Total Area Position: Tibia, Change at EOT (up to Month 36)
|
-1.21 Millimeter square (mm^2)
Standard Deviation 6.391
|
SECONDARY outcome
Timeframe: At Month 12, and EOT (up to Month 36)Population: Safety population consisted of all enrolled participants who received at least dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Bone histology parameters consisted of adjusted apposition rate and cancellous minimum apposition rate. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=4 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Mean Bone Histology (Biopsy) of Adjusted Apposition Rate and Cancellous Minimum Apposition Rate at Month 12, and EOT (up to Month 36)
Adjusted Apposition rate: At Month 12
|
0.207 Micrometer per day (mcm/d)
Standard Deviation 0.2043
|
|
Mean Bone Histology (Biopsy) of Adjusted Apposition Rate and Cancellous Minimum Apposition Rate at Month 12, and EOT (up to Month 36)
Adjusted Apposition rate: At EOT (up to Month 36)
|
0.273 Micrometer per day (mcm/d)
Standard Deviation 0.2125
|
|
Mean Bone Histology (Biopsy) of Adjusted Apposition Rate and Cancellous Minimum Apposition Rate at Month 12, and EOT (up to Month 36)
Cancellous Min Apposition Rate: At Month 12
|
0.453 Micrometer per day (mcm/d)
Standard Deviation 0.1604
|
|
Mean Bone Histology (Biopsy) of Adjusted Apposition Rate and Cancellous Minimum Apposition Rate at Month 12, and EOT (up to Month 36)
Cancellous Min Apposition Rate: At EOT (up to Month 36)
|
0.485 Micrometer per day (mcm/d)
Standard Deviation 0.1455
|
SECONDARY outcome
Timeframe: At Month 12, and EOT (up to Month 36)Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Bone histology parameters consisted of bone formation rate. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits. Here, "mcm\^3/mcm\^2/d" is abbreviated as micro cubic meter per micro square meter per day.
Outcome measures
| Measure |
rhPTH(1-84)
n=4 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Mean Bone Histology (Biopsy) of Bone Formation Rate at Month 12, and EOT (up to Month 36)
Bone Formation Rate: At Month 12
|
0.0360 mcm^3/mcm^2/d
Standard Deviation 0.04233
|
|
Mean Bone Histology (Biopsy) of Bone Formation Rate at Month 12, and EOT (up to Month 36)
Bone Formation Rate: At EOT (up to Month 36)
|
0.0665 mcm^3/mcm^2/d
Standard Deviation 0.07011
|
SECONDARY outcome
Timeframe: At Month 12, and EOT (up to Month 36)Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Bone histology parameters consisted of cancellous bone volume, cancellous eroded surface, cancellous mineral surface, and cancellous osteoid surface. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=4 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Cancellous Bone Volume: At Month 12
|
32.863 Percentage of bone histology
Standard Deviation 9.3280
|
|
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Cancellous Bone Volume: At EOT (up to Month 36)
|
34.988 Percentage of bone histology
Standard Deviation 8.7210
|
|
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Cancellous Eroded Surface: At Month 12
|
10.373 Percentage of bone histology
Standard Deviation 5.1763
|
|
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Cancellous Eroded Surface: At EOT (up to Month 36)
|
12.575 Percentage of bone histology
Standard Deviation 6.1034
|
|
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Cancellous Mineral Surface: At Month 12
|
6.973 Percentage of bone histology
Standard Deviation 6.3212
|
|
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Cancellous Mineral Surface: At EOT (up to Month 36)
|
12.028 Percentage of bone histology
Standard Deviation 11.3497
|
|
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Cancellous Osteoid Surface: At Month 12
|
17.863 Percentage of bone histology
Standard Deviation 14.2300
|
|
Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
Cancellous Osteoid Surface: At EOT (up to Month 36)
|
21.803 Percentage of bone histology
Standard Deviation 14.0379
|
SECONDARY outcome
Timeframe: At Month 12, and EOT (up to Month 36)Population: Safety population consisted of all enrolled participants who received at least 1 dose of rhPTH(1-84) regardless of study (SHP634-402 or AAAE0544 \[NCT01199614\] core study). Here, overall number of participants analyzed refer to the participants evaluable for this outcome measure and "number analyzed" refer to participants evaluable for this outcome at given categories. Due to the FDA recall, no participant received rhPTH for more than 36 months in the study.
Bone histology parameters consisted of cancellous osteoid thickness and cortical width. An optional transiliac bone biopsy was performed for willing participants, at the discretion of the investigator a maximum of three time. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.
Outcome measures
| Measure |
rhPTH(1-84)
n=4 Participants
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Mean Bone Histology (Biopsy) of Cancellous Osteoid Thickness and Cortical Width at Month 12, and EOT (up to Month 36)
Cancellous Osteoid Thickness: At Month 12
|
6.667 Micrometer (mcm)
Standard Deviation 2.9913
|
|
Mean Bone Histology (Biopsy) of Cancellous Osteoid Thickness and Cortical Width at Month 12, and EOT (up to Month 36)
Cancellous Osteoid Thickness: At EOT (up to Month 36)
|
6.667 Micrometer (mcm)
Standard Deviation 2.9913
|
|
Mean Bone Histology (Biopsy) of Cancellous Osteoid Thickness and Cortical Width at Month 12, and EOT (up to Month 36)
Cortical Width: At Month 12
|
668.677 Micrometer (mcm)
Standard Deviation 277.1239
|
|
Mean Bone Histology (Biopsy) of Cancellous Osteoid Thickness and Cortical Width at Month 12, and EOT (up to Month 36)
Cortical Width: At EOT (up to Month 36)
|
698.913 Micrometer (mcm)
Standard Deviation 234.2120
|
Adverse Events
rhPTH(1-84)
Serious events: 6 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
rhPTH(1-84)
n=39 participants at risk
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Cardiac disorders
Angina pectoris
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Gastrointestinal disorders
Hiatus hernia
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Hepatobiliary disorders
Cholecystitis
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Clostridium difficile colitis
|
2.6%
1/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Gastroenteritis
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Post procedural infection
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Pyelonephritis
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Upper respiratory tract infection
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Urinary tract infection
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Injury, poisoning and procedural complications
Hypobarism
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
7.7%
3/39 • Number of events 8 • From start of study drug administration up to end of study (up to 38 months)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.6%
1/39 • Number of events 1 • From start of study drug administration up to end of study (up to 38 months)
|
Other adverse events
| Measure |
rhPTH(1-84)
n=39 participants at risk
Participants received 25 micrograms (mcg) of rhPTH(1-84) with an upwards increments to 50, 75, and 100 mcg subcutaneous (SC) injection to the thigh via a multi-dose pen injector device once daily for 36 months of treatment period. The dose of rhPTH(1 84) was individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion at investigator's discretion to achieve a serum calcium level in the lower half of the normal range (8 and 9 milligram/deciliter \[mg/dL\]).
|
|---|---|
|
Endocrine disorders
Hypothyroidism
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Gastrointestinal disorders
Constipation
|
7.7%
3/39 • Number of events 4 • From start of study drug administration up to end of study (up to 38 months)
|
|
Gastrointestinal disorders
Diarrhoea
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Gastrointestinal disorders
Nausea
|
10.3%
4/39 • Number of events 5 • From start of study drug administration up to end of study (up to 38 months)
|
|
Immune system disorders
Drug hypersensitivity
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Immune system disorders
Seasonal allergy
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Bronchitis
|
7.7%
3/39 • Number of events 4 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Influenza
|
12.8%
5/39 • Number of events 5 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Nasopharyngitis
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Pharyngitis streptococcal
|
12.8%
5/39 • Number of events 6 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Pneumonia
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Sinusitis
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Tooth infection
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Infections and infestations
Urinary tract infection
|
12.8%
5/39 • Number of events 5 • From start of study drug administration up to end of study (up to 38 months)
|
|
Injury, poisoning and procedural complications
Foot fracture
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Injury, poisoning and procedural complications
Hand fracture
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Investigations
Alanine aminotransferase increased
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Investigations
Aspartate aminotransferase increased
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
25.6%
10/39 • Number of events 17 • From start of study drug administration up to end of study (up to 38 months)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
7.7%
3/39 • Number of events 5 • From start of study drug administration up to end of study (up to 38 months)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
3/39 • Number of events 4 • From start of study drug administration up to end of study (up to 38 months)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.7%
3/39 • Number of events 3 • From start of study drug administration up to end of study (up to 38 months)
|
|
Nervous system disorders
Headache
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Nervous system disorders
Hypoaesthesia
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Psychiatric disorders
Anxiety
|
41.0%
16/39 • Number of events 17 • From start of study drug administration up to end of study (up to 38 months)
|
|
Psychiatric disorders
Depression
|
20.5%
8/39 • Number of events 8 • From start of study drug administration up to end of study (up to 38 months)
|
|
Psychiatric disorders
Insomnia
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Skin and subcutaneous tissue disorders
Dermatitis allergic
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
|
Vascular disorders
Hypertension
|
15.4%
6/39 • Number of events 7 • From start of study drug administration up to end of study (up to 38 months)
|
|
Vascular disorders
Varicose vein
|
5.1%
2/39 • Number of events 2 • From start of study drug administration up to end of study (up to 38 months)
|
Additional Information
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