A Study to Investigate the Safety and Tolerability of NPSP558, for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study in Hungary

Study Overview
=================
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.

Official Title
-----------------
A 6-Month Open-label Study Investigating the Safety and Tolerability of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH [1-84]), for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study

Conditions
-----------------
Hypoparathyroidism

Intervention / Treatment
-----------------
* Drug: NPSP558


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who meet all the following inclusion criteria can be enrolled into this study: Signed and dated informed consent form (ICF) before any study-related procedures are performed 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 Able to perform daily SC self-injections of study medication (or have a designee perform injection) via a multidose injection pen into the thigh Willingness and ability to understand and comply with the protocol 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 Exclusion Criteria: Patients who meet any of the following exclusion criteria at baseline (Visit 1) are not eligible for enrollment in this study: Any condition that, in the investigator's opinion after consultation with the sponsor, would preclude the safe use of NPSP558 Any disease or condition in the opinion of the investigator that has a high probability of precluding the patient from completing the study or where the patient cannot or will not appropriately comply with study requirements Pregnant or lactating woman

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPSP558<br> | Drug: NPSP558<br>* 50, 75, 100 μg<br>* Other names: REPEAT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 24 Weeks | 
| Mean Change From Baseline in 24-hour Urine Calcium Excretion |  | 24 Weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PTH 1-84, Hypoparathyroidism, NPSP558, Parathyroid Hormone 1-84