Hypoparathyroidism
Conditions
Keywords
Hypoparathyroidism, rhPTH[1-84], NPSP558
Brief summary
Use of PTH (1-84) a recombinant hormone in 25 µg or 50 µg doses for the treatment of adults with hypoparathyroidism. The use of PTH (1-84) should result in a decrease of calcium and vitamin D supplements.
Detailed description
Patients with a history of Hypoparathyroidism will be randomized to receive study drug for 8 weeks, which will be injected daily in either thigh. During that time they will be monitored for safety (specifically calcium levels in blood or urine). In addition, the patients' intake of Vitamin D and Calcium will be measured.
Interventions
DRUGNPSP558
All patients will inject NPSP558 25 or 50 µg SC QD into alternating thighs in the morning via a multidose injection pen device.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Previously completed 24 weeks of therapy and 4 weeks of follow-up in the REPLACE study 2. With regard to female patients: women who are postmenopausal or willing to use two medically acceptable methods of contraception for the duration of the study with pregnancy testing conducted at every scheduled office visit 3. Total serum calcium ≤ ULN based on local laboratory results prior to randomization 4. Serum 25(OH) vitamin D ≤ 1.5 times the ULN within approximately 8 weeks prior to randomization Main
Exclusion criteria
1. Any disease or condition that, in the opinion of the investigator, has a high probability of precluding the patient from completing the study or being able to appropriately comply with study requirements 2. Use of raloxifene hydrochloride or intravenous (IV) bisphosphonates since the end of participation in the REPLACE trial 3. Chronic (ie, ≥ 1 month exposure) use of systemic corticosteroids, oral bisphosphonates, calcitonin, fluoride tablets, or cinacalcet hydrochloride 4. Pregnant or lactating women 5. Any condition that would, in the investigator's opinion in consultation with the sponsor, preclude the safe use of PTH 6. Use of any experimental drug other than NPSP558 within 3 months of baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 8, Based on Investigator Prescribed Data. | 8 Weeks | The triple efficacy endpoint criteria were defined as a reduction from baseline in oral calcium to ≤ 500 mg/day, a reduction from baseline in calcitriol dose to ≤ 0.25 µg/day, and an albumin-corrected total serum calcium level between 7.5 mg/dL and the upper limit of the laboratory normal range. The analysis of primary endpoint was based on investigator prescribed data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Who Met the Triple Efficacy Endpoint Criteria at Week 8. | 8 Weeks | The triple efficacy endpoint criteria were defined as at least a 50% reduction from the baseline in oral calcium dose and at least a 50% reduction from the baseline in active vitamin D dose and an albumin-corrected total serum calcium concentration that was maintained or normalized compared to the baseline value (≥ 7.5 mg/dL) and did not exceed the upper limit of the laboratory normal range. The analysis of primary efficacy endpoint was based on investigator prescribed data |
Countries
United States
Participant flow
Recruitment details
42 Subjects enrolled between 2/2011 and 9/2011 at 11 sites in the US.
Pre-assignment details
Subjects who completed 24 wks of treatment and 4 wks follow-up in the REPLACE Study (NCT00732615) or received 2 single doses in Phase I Study C09-002 followed by a 4-wk washout, or enrolled in the REPLACE Study and entered into the optimization phase, but were not randomized due to the close of randomization; or were new to the NPSP558 program.
Participants by arm
| Arm | Count |
|---|---|
| NPSP558 - 25 µg Dose NPSP558: Recombinant Human Parathyroid hormone (rhPTH\[1-84\]) 25 mcg subcutaneously daily | 19 |
| NPSP558 - 50 µg Dose NPSP558: Recombinant Human Parathyroid hormone (rhPTH\[1-84\]) 50 mcg subcutaneously daily | 23 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | NPSP558 - 25 µg Dose | NPSP558 - 50 µg Dose | Total |
|---|---|---|---|
| Age, Customized 45 to 64 years | 10 Participants | 15 Participants | 25 Participants |
| Age, Customized < 45 years | 6 Participants | 8 Participants | 14 Participants |
| Age, Customized >/= 65 years | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 17 Participants | 22 Participants | 39 Participants |
| Region of Enrollment United States | 19 Participants | 23 Participants | 42 Participants |
| Sex: Female, Male Female | 16 Participants | 19 Participants | 35 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 19 | 17 / 23 |
| serious Total, serious adverse events | 0 / 19 | 0 / 23 |
Outcome results
Primary
Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 8, Based on Investigator Prescribed Data.
The triple efficacy endpoint criteria were defined as a reduction from baseline in oral calcium to ≤ 500 mg/day, a reduction from baseline in calcitriol dose to ≤ 0.25 µg/day, and an albumin-corrected total serum calcium level between 7.5 mg/dL and the upper limit of the laboratory normal range. The analysis of primary endpoint was based on investigator prescribed data.
Time frame: 8 Weeks
Population: Intent to Treat (ITT) population, which includes all randomized subjects who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPSP558 - 25 µg Dose | Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 8, Based on Investigator Prescribed Data. | 21.1 percentage of participants |
| NPSP558 - 50 µg Dose | Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 8, Based on Investigator Prescribed Data. | 26.1 percentage of participants |
Comparison: The null hypothesis corresponding to the primary efficacy endpoint is that the percentages of subjects who meet the endpoint criteria are the same for both dose arms. This sample size for this study was not based on the statistical considerations.p-value: >0.99995% CI: [-20.6, 30.7]Fisher Exact
Secondary
The Percentage of Subjects Who Met the Triple Efficacy Endpoint Criteria at Week 8.
The triple efficacy endpoint criteria were defined as at least a 50% reduction from the baseline in oral calcium dose and at least a 50% reduction from the baseline in active vitamin D dose and an albumin-corrected total serum calcium concentration that was maintained or normalized compared to the baseline value (≥ 7.5 mg/dL) and did not exceed the upper limit of the laboratory normal range. The analysis of primary efficacy endpoint was based on investigator prescribed data
Time frame: 8 Weeks
Population: Intent to Treat (ITT) population, which includes all randomized subjects who received at least 1 dose of study drug and had at least 1 post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NPSP558 - 25 µg Dose | The Percentage of Subjects Who Met the Triple Efficacy Endpoint Criteria at Week 8. | 10.5 percentage of participants |
| NPSP558 - 50 µg Dose | The Percentage of Subjects Who Met the Triple Efficacy Endpoint Criteria at Week 8. | 26.1 percentage of participants |
Comparison: The null hypothesis corresponding to this endpoint is that the percentages of subjects who meet the endpoint criteria are the same for both dose arms.p-value: 0.258Fisher Exact