Hypoparathyroidism
Conditions
Keywords
PTH 1-84, Hypoparathyroidism, NPSP558, Parathyroid Hormone 1-84
Brief summary
This study is designed to evaluate the effect of 6-months of treatment with NPSP558 in reducing requirements for supplemental oral calcium and active vitamin D, while maintaining stable total serum calcium levels in adult subjects with hypoparathyroidism.
Detailed description
Subjects either must have previously completed NPSP558 Study CL1-11-040 (REPLACE) including 24 weeks of active therapy and 4 weeks of follow-up to Week 28 prior to enrolling in this study or have enrolled in REPLACE and dropped out during optimization, but currently meet inclusion/exclusion criteria for REPLACE.
Interventions
DRUGNPSP558
50, 75, 100 μg
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Patients who meet all the following inclusion criteria can be enrolled into this study: 1. Signed and dated informed consent form (ICF) before any study-related procedures are performed 2. Previously completed 24 weeks of therapy and 4 weeks of follow-up in the REPLACE study, OR Enrolled in REPLACE and dropped out during optimization, but currently meet inclusion/
Exclusion criteria
for REPLACE 3. Able to perform daily SC self-injections of study medication (or have a designee perform injection) via a multidose injection pen into the thigh 4. Willingness and ability to understand and comply with the protocol 5. Women who are: (1) postmenopausal defined as 12 months amenorrhea with appropriate serum follicle stimulating hormone (FSH) levels (\> 40 IU/L); (2) surgically sterilized; OR (3) of childbearing potential with a negative pregnancy test at screening and who consent to use two acceptable methods of contraception for the duration of the study, with pregnancy testing at every scheduled visit during the treatment period . Female partners (who are of childbearing potential) of male study patients must also use acceptable forms of contraception during their partner's participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 24, Based on Investigator Prescribed Data. | 24 Weeks | A ≥ 50% reduction from baseline in dose of oral calcium or an oral calcium dose of ≤ 500 mg and a ≥ 50% reduction from baseline in dose of oral active vitamin D (calcitriol dose of ≤ 0.25 μg/day or alphacalcidol dose of ≤ 0.50 μg/day) and a total serum calcium concentration that was normalized or maintained compared to the baseline value and did not exceed the ULN of the central laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Changes From Baseline in Active Vitamin D Dosages at Each Visit | 24 Weeks | — |
| Mean Percentage Changes From Baseline in Oral Calcium at Each Visit | 24 Weeks | — |
| Proportion of Patients Achieving the Primary Endpoint at Each Visit | 24 Weeks | A ≥ 50% reduction from baseline in dose of oral calcium or an oral calcium dose of ≤ 500 mg and a ≥ 50% reduction from baseline in dose of oral active vitamin D (calcitriol dose of ≤ 0.25 μg/day or alphacalcidol dose of ≤ 0.50 μg/day) and a total serum calcium concentration that was normalized or maintained compared to the baseline value and did not exceed the ULN of the central laboratory. |
| Mean Change From Baseline in 24-hour Urine Calcium Excretion | 24 Weeks | — |
Countries
Hungary
Participant flow
Recruitment details
24 Subjects were enrolled between 8/2011 to 5/2012 at 3 Clinical sites in Hungary.
Pre-assignment details
Subjects previously completed 24 weeks of therapy and 4 weeks of follow-up in the REPLACE study, or enrolled in REPLACE and dropped out during optimization, but currently met inclusion/exclusion criteria for REPLACE.
Participants by arm
| Arm | Count |
|---|---|
| NPSP558 NPSP558: Recombinant Human Parathyroid hormone (rhPTH\[1-84\]) 50, 75, or 100 mcg subcutaneously daily. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | NPSP558 |
|---|---|
| Age, Customized 45 to 64 years | 17 Participants |
| Age, Customized < 45 years | 6 Participants |
| Age, Customized ≥ 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment Hungary | 24 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 24, Based on Investigator Prescribed Data.
A ≥ 50% reduction from baseline in dose of oral calcium or an oral calcium dose of ≤ 500 mg and a ≥ 50% reduction from baseline in dose of oral active vitamin D (calcitriol dose of ≤ 0.25 μg/day or alphacalcidol dose of ≤ 0.50 μg/day) and a total serum calcium concentration that was normalized or maintained compared to the baseline value and did not exceed the ULN of the central laboratory.
Time frame: 24 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPSP558 | Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 24, Based on Investigator Prescribed Data. | 75.0 percentage of participants |
Secondary
Mean Change From Baseline in 24-hour Urine Calcium Excretion
Time frame: 24 Weeks
Population: The Intent-to-treat population, which includes all subjects who received at least one dose of study drug and had at least one efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NPSP558 | Mean Change From Baseline in 24-hour Urine Calcium Excretion | Week 8 | -64.58 mg/24 hour | Standard Deviation 188.42 |
| NPSP558 | Mean Change From Baseline in 24-hour Urine Calcium Excretion | Week 24 | -51.53 mg/24 hour | Standard Deviation 183.41 |
Secondary
Mean Percentage Changes From Baseline in Active Vitamin D Dosages at Each Visit
Time frame: 24 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NPSP558 | Mean Percentage Changes From Baseline in Active Vitamin D Dosages at Each Visit | Week 2 | -47.08 percentage of change | Standard Deviation 31.566 |
| NPSP558 | Mean Percentage Changes From Baseline in Active Vitamin D Dosages at Each Visit | Week 4 | -80.38 percentage of change | Standard Deviation 16.688 |
| NPSP558 | Mean Percentage Changes From Baseline in Active Vitamin D Dosages at Each Visit | Week 8 | -96.70 percentage of change | Standard Deviation 7.865 |
| NPSP558 | Mean Percentage Changes From Baseline in Active Vitamin D Dosages at Each Visit | Week 16 | -96.18 percentage of change | Standard Deviation 11.521 |
| NPSP558 | Mean Percentage Changes From Baseline in Active Vitamin D Dosages at Each Visit | Week 24 | -97.92 percentage of change | Standard Deviation 10.206 |
Secondary
Mean Percentage Changes From Baseline in Oral Calcium at Each Visit
Time frame: 24 Weeks
Population: The Intent-to-treat population, which includes all subjects who received at least one dose of study drug and had at least one efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NPSP558 | Mean Percentage Changes From Baseline in Oral Calcium at Each Visit | Week 2 | -8.3 percentage of change | Standard Deviation 36.2 |
| NPSP558 | Mean Percentage Changes From Baseline in Oral Calcium at Each Visit | Week 4 | -46.4 percentage of change | Standard Deviation 35.57 |
| NPSP558 | Mean Percentage Changes From Baseline in Oral Calcium at Each Visit | Week 8 | -71.5 percentage of change | Standard Deviation 33.14 |
| NPSP558 | Mean Percentage Changes From Baseline in Oral Calcium at Each Visit | Week 16 | -71.7 percentage of change | Standard Deviation 38.6 |
| NPSP558 | Mean Percentage Changes From Baseline in Oral Calcium at Each Visit | Week 24 | -76.0 percentage of change | Standard Deviation 40.48 |
Secondary
Proportion of Patients Achieving the Primary Endpoint at Each Visit
A ≥ 50% reduction from baseline in dose of oral calcium or an oral calcium dose of ≤ 500 mg and a ≥ 50% reduction from baseline in dose of oral active vitamin D (calcitriol dose of ≤ 0.25 μg/day or alphacalcidol dose of ≤ 0.50 μg/day) and a total serum calcium concentration that was normalized or maintained compared to the baseline value and did not exceed the ULN of the central laboratory.
Time frame: 24 Weeks
Population: The Intent-to-treat population, which includes all subjects who received at least one dose of study drug and had at least one efficacy measurement .
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NPSP558 | Proportion of Patients Achieving the Primary Endpoint at Each Visit | Week 2 | 20.8 percentage of participants |
| NPSP558 | Proportion of Patients Achieving the Primary Endpoint at Each Visit | Week 4 | 50.0 percentage of participants |
| NPSP558 | Proportion of Patients Achieving the Primary Endpoint at Each Visit | Week 8 | 70.8 percentage of participants |
| NPSP558 | Proportion of Patients Achieving the Primary Endpoint at Each Visit | Week 16 | 83.3 percentage of participants |
| NPSP558 | Proportion of Patients Achieving the Primary Endpoint at Each Visit | Week 24 | 83.3 percentage of participants |