An Open-Label Randomized Crossover Study to Assess the Pharmacokinetic and Pharmacodynamic Profiles of Once-Daily and Twice-Daily dose Regimens of recombinant human Parathyroid Hormone (rhPTH[1-84]) Administered Subcutaneously to Subjects with Hypoparathyroidism

Inclusion Criteria
History of hypoparathyroidism for greater than or equal to 12 months, post-diagnosis, inclusive of historical biochemical evidence of hypocalcemia with concomitant serum intact PTH concentrations below the lower limit of the laboratory normal range
Requirement for supplemental oral calcium treatment greater than or equal to 1000 mg per day
Requirement for therapy with active forms of vitamin D at a minimum dose of greater than or equal to 0.25 micrograms per day
Male or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential
Exclusion Criteria
Participation in any other investigational drug study in which the last dose of investigational drug occurred within 3 months prior to Day 1 of Treatment Period 1
Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal gastrointestinal, immunologic, hematologic, endocrine (with the exception of the condition under study), or neurologic system(s) or psychiatric disease as determined by the investigator
Known history of hypoparathyroidism resulting from an activation mutation in the CaSR gene or impaired responsiveness to PTH
Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, including but not limited to, active hyperthyroidism; poorly controlled insulin-dependent diabetes mellitus or type 2 diabetes mellitus; 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, bone metastases or a history of skeletal malignancies; primary or secondary hyperparathyroidism; a history of parathyroid carcinoma; hypopituitarism, acromegaly; or multiple endocrine neoplasia types 1 and 2, as determined by the investigator
Subjects who are at increased baseline risk for osteosarcoma such as subjects with Paget's disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult subjects with open epiphyses, subjects with hereditary disorders predisposing to osteosarcoma or subjects with a prior history of external beam or implant radiation therapy involving the skeleton
Subjects who have a known history of hypercalcemia during initiation of treatment with PTH, PTH analogues or fragments of PTH
Subjects who have a known history of hypocalcemia following abrupt withdrawal of treatment with PTH, PTH analogues or fragments of PTH
Subjects dependent on regular parenteral calcium infusions to maintain calcium homeostasis within 3 months prior to enrollment, as determine by the investigator
Any medical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for this study
Positive test result for any of the following viral infections at study screening: hepatitis B surface antigen, hepatitis C, HIV
Known significant bleeding diathesis that could preclude multiple venipunctures as determined by the investigator
Has taken herbal supplements or combination products with herbal supplements within 14 days of investigational product adminstration
History of a clinically significant illness during the 4 weeks prior to dosing
History of any clinically significant surgery or procedure within the past 8 weeks
History of an allergic response(s) to PTH or PTH analogs, or other clinically significant allergies