Use of NPSP558 in the Treatment of Hypoparathyroidism

Hypoparathyroidism Clinical Trial

— REPLACE  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Investigate the Use of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH[1-84]) for the Treatment of Adults With Hypoparathyroidism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00732615
• Other study ID #: CL1-11-040
• Secondary ID: 2008-005063-34
• Status: Completed
• Phase: Phase 3
• Start date: December 18, 2008
• Est. completion date: September 28, 2011

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Use of PTH (1-84) a recombinant hormone in escalating doses for the treatment of adults with hypoparathyroidism. The use of PTH should result in a decrease of calcium and vitamin D supplements.

Description:

Patients with a history of hypoparathyroidism will be randomized to receive placebo or study drug for 24 weeks, which will be injected daily in either thigh. During that time they will be monitored for safety (specifically, calcium levels in the blood and urine). In addition, the patients' intake of Vitamin D and calcium will be measured.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: September 28, 2011
• Est. primary completion date: September 28, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria Patients who meet all of the following inclusion criteria can be enrolled and potentially

randomized into this study:

• Adult males or females 18 to 85 years of age (prior to screening)
• History of hypoparathyroidism for = 18 months
• Requirement for vitamin D metabolite/analog therapy with calcitriol =0.25 µg per day or alphacalcidol =0.50 µg per day prior to randomization. Requirement for supplemental oral calcium treatment = 1000 mg per day over and above normal dietary calcium intake
• Serum thyroid function tests within normal laboratory limits at screening
• Serum magnesium levels within laboratory normal limits
• Serum 25-hydroxyvitamin D [25(OH)D] level = 1.5-fold the laboratory upper limit of normal
• Creatinine clearance > 30 mL/min on two separate measurements OR creatinine clearance > 60 mL/min AND serum creatinine < 1.5 mg/dL
• With regard to female patients: women who are postmenopausal and women who are surgically sterilized can be enrolled. Women of childbearing potential must have a negative pregnancy test at Randomization and be willing to use two medically acceptable methods of contraception for the duration of the study. Exclusion Criteria Patients who have any of the following during the screening visit are not eligible for

enrollment in this study:

• Known history of hypoparathyroidism resulting from an activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism)
• Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as active hyperthyroidism, Paget's disease, insulin dependent diabetes mellitus (IDDM) or poorly controlled Type II diabetes mellitus (HbA1C > 8%), severe and chronic cardiac, liver or renal disease, Cushing's syndrome, neuromuscular disease such as rheumatoid arthritis, myeloma, pancreatitis, malnutrition, rickets, recent prolonged immobility, active malignancy, primary or secondary hyperparathyroidism, a history of parathyroid carcinoma, hypopituitarism, acromegaly, or multiple endocrine neoplasia types I and II
• Patients with a history of thyroid cancer must be documented to be disease-free for a period of at least 5 years
• Patients dependent on regular parenteral calcium infusions (eg calcium gluconate) to maintain calcium homeostasis
• Patients that have undergone gastric resection or have active peptic ulcer disease requiring medical therapy
• Use of prohibited medications such as loop and thiazide diuretics, raloxifene hydrochloride, lithium, estrogens and progestins for hormone replacement therapy,methotrexate, or systemic corticosteroids within respective prohibited periods
• Previous treatment with PTH-like drugs, including PTH(1-84), PTH(1-34) or other N-terminal fragments or analogs of PTH or PTH-related protein within 6 months prior to screening
• Other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets, or cinacalcet hydrochloride within the prohibited period
• Use of oral bisphosphonates within the previous 6 months or IV bisphosphonate preparations within the previous 12 months prior to screening
• Seizure disorder/epilepsy with a history of a seizure within the previous 6 months prior to screening
• Presence of open epiphyses
• Irradiation (radiotherapy) to the skeleton within 5 years
• Serum 25-hydroxyvitamin D levels greater than 1.5-fold the laboratory upper limit of normal
• Participation in any other investigational trial in which receipt of investigational drug or device occurred within 6 months prior to screening for this study
• Pregnant or lactating women
• History of diagnosed drug or alcohol dependence within the previous 3 years
• Clinical history of renal calculi within the past 12 months
• History of gout
• Disease processes that may adversely affect gastrointestinal absorption, including but not limited to short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn's disease
• Chronic/severe cardiac disease including but not limited to cardiac insufficiency, arrhythmias, bradycardia (resting heart rate < 60 beats/minute), or hypotension (systolic and diastolic blood pressures < 100 and 60 mmHg, respectively)
• History of cerebrovascular accident (CVA).

Related Conditions & MeSH terms

• Hypoparathyroidism

Intervention

Drug:
• Placebo
Placebo for subcutaneous injection
• NPSP558
Parathyroid hormone 50, 75, or 100 mcg injectable subcutaneously daily

Locations

Country	Name	City	State
Belgium	Chetre Hospitalier Universitaire de Liege	Liege
Canada	Heritage Medical Research Clinic	Calgary	Alberta
Canada	Capital District Health Authority, QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Oakville Bone Center	Oakville	Ontario
Denmark	Aarhus University Hospital	Aarhus
Denmark	Odense University Hospital	Odense
France	Hôpital Européen Georges Pompidou	Paris
Hungary	Semmelweis University Medical School	Budapest
Hungary	University of Pécs, School of Medicine	Pécs
Hungary	University of Szeged	Szeged
Italy	University Hospital of Careggi	Firenze
United Kingdom	Royal Liverpool University Hospital	Liverpool
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati Bone Health and Osteoporosis Center	Cincinnati	Ohio
United States	Michigan Bone and Mineral Clinic PC	Detroit	Michigan
United States	Physicians East	Greenville	North Carolina
United States	Palm Springs Research Institute	Hialeah	Florida
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Advance Medical Research LLC	Lakewood	California
United States	Columbia University Medical Center	New York	New York
United States	Diabetes Associates	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Cetero Research DGD Research Inc.	San Antonio	Texas
United States	University of California-San Francisco VA Medical Center	San Francisco	California
United States	Mayo Clinic-Scottsdale	Scottsdale	Arizona
United States	University Physicians Group	Staten Island	New York
United States	The Vancouver Clinic	Vancouver	Washington
United States	Hillcrest Family Health Center	Waco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  France,  Hungary,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage of Subjects Who Met the Triple Efficacy Endpoint Criteria at Week 24.	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.	Week 24 of dosing
Secondary	Percentage Changes From Baseline in Daily Calcium Dose at Week 24.	The analysis of this endpoint was based on investigator prescribed data.	24 Weeks
Secondary	Proportion of Subjects Who Achieved Independence From Active Vitamin D and an Oral Calcium Dose of = 500 mg/Day at Week 24.	Subjects Who Achieved Independence from Active Vitamin D Usage and with Calcium Dose of 500 mg/day or less. This analysis was based on Investigator Prescribed Data.	24 Weeks
Secondary	Percentage of Subjects With Any Clinical Symptoms of Hypocalcemia During Weeks 16-24.	Clinical symptoms were a selected group of adverse events that occurred during study weeks 16 through 24. The group of terms were defined by key opinion leaders and documented in study protocol.	8 Weeks