Please select the eligibility criteria that correspond to the clinical trial below.
Title: Comparing Pump vs. Subcutaneous Injection Delivery of PTH 1-34 in the Management of Chronic Hypoparathyroidism
Brief Summary: This study will evaluate the safety, biological activity, and pharmacokinetics of PTH delivered by subcutaneous injection compared with an infusion pump. We anticipate pump delivery of PTH will be more physiologic because it mimics normal parathyroid gland secretion of PTH. We expect that pump delivery will simultaneously normalize blood and urine calcium, phosphorus and magnesium levels with minimal or no fluctuations throughout the day. Pump therapy will require lower PTH doses and should normalize markers of bone turnover. We expect the improved metabolic control during pump therapy will be especially evident in patients with more severe forms of hypoparathyrodism where there is an unmet need for improved therapy.


Options:
A: 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.
B: 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).
C: * INCLUSION CRITERIA:

This study will include patients of both genders (ages 7-70) with biochemically confirmed chronic hypoparathyroidism of at least one year duration. Twenty-four subjects will be enrolled.

EXCLUSION CRITERIA:

Subjects who meet any of the following criteria are not eligible for the study:

* Pregnancy
* Patients who are calcium infusion dependent and/or do not respond to calcitriol therapy to maintain normal levels of serum calcium will be excluded.
* Seizure disorder requiring antiepileptic medications.
D: Inclusion Criteria:

* A low endogenous PTH production as verified by low plasma levels of intact PTH, necessitating treatment with 1alpha-hydroxylated vitamin D analogs.
* At least one years of continuous alphacalcidol, calcitriol, or dihydrotachysterol treatment prior to study entry.
* Prior to start of study, participants are required to have received a daily supplement of at least 400 IU (10 microgram) of vitamin D (ergocalciferol or cholecalciferol) for at least 3 months or 25hydroxyvitamin D levels above 50 nmol/l. Subjects may be treated with ergocalciferol or cholecalciferol during a run-in period of three months before entering the study.
* Normal plasma magnesium level (If not, magnesium supplements may be provided during a 3 months run in period).
* Plasma calcium levels within the normal reference range or slightly below (P-Ca ionized 1.00 to 1.30).
* Use of safe contraceptive methods (fertile women).
* Speak and read Danish.

Exclusion Criteria:

* Known allergic reactions to any of the compounds in the trial medication.
* Severely impaired renal function (plasma creatinine \> 200 micromol/l).
* Severely impaired hepatic function (Plasma alanine aminotransferase (ALAT) \> 100 U/l and/or alkaline phosphatase \> 400 U/l).
* Previous or present malignancies (except a treated skin cancer that is not melanoma or treated carcinoma in situ, 2 years since last therapy).
* Prior radiation therapy involving the skeleton.
* Current treatment with raloxifene, calcitonin, systemic corticosteroids above 5 mg a day, fluoride, lithium, PTH, or digoxin.
* Treatment with anticonvulsant's (within the last 2 years).
* Immobilization (more than two week within the last 6 months).
* Granulomatous disease.
* Paget's disease of bone.
* Pregnancy / planned within the next year. Hospitalized due to chronic drug or alcohol abuse. Severe malabsorption syndrome.
* Major medical or social problems that will be likely to preclude participation for one year.
* Unwillingness to participate.

Answer: C