Hypoparathyroidism MedDRA version: 9.1 Level: LLT Classification code 10021041 Term: Hypoparathyroidism
Conditions
Interventions
Product Name: Recombinant Human Parathyroid Hormone [rhPTH(1-84)]
Product Code: NPSP 558
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Parathyroid Hormone
CAS
Sponsors
NPS Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult males or females 18 to 65 years of age. Those 1000 mg per day over and above normal dietary calcium intake; 4. Serum thyroid function tests within normal laboratory limits at screening. For patients on thyroid hormone replacement therapy, the dose must have been stable for at least 3 months prior to screening; 5. Serum magnesium levels should be within normal laboratory limits; 6. Serum 25-hydroxyvitamin D [25(OH)D] level = 120 ng/mL (normal range 20 80 ng/mL); 7. Creatinine clearance > 30 mL/min on two separate measurements at screening OR creatinine clearance > 60 mL/min AND serum creatinine =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Hypoparathyroidism resulting from an activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism); 2. 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; 3. To be eligible, patients with a history of thyroid cancer must be documented to be disease-free for a period of at least 5 years. 4. Patients dependent on regular parenteral calcium infusions (eg calcium gluconate) to maintain calcium homeostasis; 5. Patients that have undergone gastric resection or have active peptic ulcer disease requiring medical therapy; 6. Use of prohibited medications such as loop diuretics, raloxifene hydrochloride, lithium, estrogens, progestins, methotrexate, or systemic corticosteroids within respective prohibited periods; 7. 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 the prohibited period; 8. Other drugs known to influence calcium and bone metabolism such as bisphosphonates, calcitonin, fluoride, or cinacalcet hydrochloride within the prohibited period; 9. Seizure disorder/epilepsy with a history of a seizure within the previous 6 months; 10. Presence of open epiphyses; 11. Irradiation to the skeleton within 5 years; 12. Serum 25-hydroxyvitamin D levels > 120 ng/mL (normal 20 – 80 ng/mL); 13. 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; 14. Participation in any other investigational trial in which receipt of investigational drug or device occurred within 30 days prior to screening for this study; 15. Women of childbearing potential unless surgically sterilized or are postmenopausal for = 2 years; 16. History of diagnosed drug or alcohol dependence within the previous 3 years; 17. Clinical history of renal calculi within the past 12 months; 18. History of gout; 19. 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; 20. 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); 21. History of cerebrovascular accident (CVA).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate, over a 24-week period, that once-daily dosing with NPSP 558 across a dose range of 50 µg, 75 µg or 100 µg SC, is a safe and effective hormone replacement therapy for the treatment of patients with hypoparathyroidism caused by surgery (thyroid, parathyroid or other neck surgery), autoimmune disease, idiopathic disease or abnormalities of parathyroid glands that reduce synthesis or secretion of PTH. ;Secondary Objective: The secondary objectives of the study are to demonstrate that 24 weeks of treatment with once-daily NPSP 558 across a dose range of 50 µg, 75 µg or 100 µg SC is associated with improvements from Baseline measurements in urinary calcium excretion.;Primary end point(s): A responder is defined as a patient that demonstrates at least a 50% reduction from Baseline amounts of oral calcium supplementation and at least a 50% reduction from Baseline amounts of vitamin D metabolite/analog therapy by Week 24 of the study. Patients should have a clinically stable serum calcium level that is established to the satisfaction of the Investigator at Baseline and is maintained or normalized by Week 24 of the study. At the end of the treatment phase it is aimed that patients should have a serum calcium that is clinically stable in the opinion of the Investigator and just below or within the lower half of the normal range. | — |
Countries
Belgium, Denmark, France, Hungary, Italy, Lithuania, United Kingdom
Outcome results
None listed