Oral PTH(1-34) PK and PD Study in Patients With Hypoparathyroidism
Oral PTH(1-34) PK and PD Study in Patients With Hypoparathyroidism
A Randomized, active comparator, two-part, partial crossover design. The study is designed to
 assess the pharmacokinetics and pharmacodynamics of EnteraBio's Oral PTH(1-34) [EB612
 (EBP05)] in adult patients with hypoparathyroidism.
-Criteria for Inclusion:

 1. Confirmed diagnosis of primary hypoparathyroidism, as defined by the European Society
 of Endocrinology as a patient with hypocalcemia and inappropriately low PTH levels. If
 the source of hypoparathyroidism is surgical or iatrogenic, diagnosis must be for more
 than 1 year. If the source of hypoparathyroidism is not surgical or iatrogenic, and
 confirmed by inappropriately low PTH levels and hypercalciuria, diagnosis does not
 have time limitations.

 2. 1, 25(OH)2D levels ≥20 ng/mL.

 3. Signed Informed Consent Form).

 4. Age 18 to 80 years with body mass index of 19 to 35 kg/m2.

 5. Patients able to adhere to the visit schedule and protocol requirements.

 Criteria for Exclusion:

 1. Known history of hypoparathyroidism resulting from an activating mutation in the
 calcium sensing receptor gene or impaired responsiveness to PTH
 (pseudohypoparathyroidism).

 2. Hemoglobin <11.5 g/dL (females) / <12.5g/dL (males) [lower limit of reference range,
 12 to 15 g/dL and 13 to 17 g/dL]

 3. Acute or chronic renal failure (estimated glomerular filtration rate <60 mL/min/1.73
 m²).

 4. Significant liver function impairment (liver enzymes above ×2 the upper limit of
 normal range).

 5. Patients with hypomagnesemia should be excluded unless serum magnesium is corrected
 prior to study initiation.

 6. Active gastrointestinal inflammatory, gastrointestinal motility disorders, and chronic
 gastritis, such as ulcerative colitis, Crohn's disease, irritable bowel syndrome,
 short bowel syndrome, celiac disease, gastroparesis, etc.

 7. Active hepatitis or acquired immunodeficiency syndrome (AIDS)/AIDS-related syndrome

 8. Any conditions or factors that, in the judgment of the Investigator, somehow may
 impact gastrointestinal absorption.

 9. Concurrent therapy with the following medications: (1) 14 days: thiazide diuretics;
 loop diuretics (2) 30 days: lithium, systemic corticosteroid; (3) 1 month: calcitonin,
 cinacalcet hydrochloride, recombinant PTH(1-84) or N-terminal PTH or PTH-related
 peptide fragments or analogs; (4) females only; changes in hormone replacement therapy
 within 2 months; (5) 3 months: methotrexate, growth hormone, digoxin; raloxifene or
 similar selective estrogen receptor modulators; (7) chronic or concurrent use of
 gastrointestinal motility modulators (domperidone, loperamide, erythromycin
 metoclopramide etc.); and (8) other concurrent therapy that, in the Investigator's
 opinion, would interfere with the evaluation of the safety or efficacy of the study
 medication.

 10. Significant drug or alcohol abuse as assessed by the PI.

 11. Treatment with any investigational product within the last 30 days or 5 half-lives (if
 known) whichever is longer.

 12. Has participated as a patient in any investigational drug study within the last 30
 days preceding the screening visit or plans to participate in another investigational
 drug study at any time during the study or within 30 days of his/her completion of
 this study.

 13. Presence of any other condition or circumstance that, in the judgment of the
 Investigator, might increase the risk to the patient or decrease the chance of
 obtaining satisfactory data to achieve the objectives of the study.

 14. Historical documented allergy to soy bean products or known hypersensitivity to the
 PTH (1-34).

 15. Patients at increased risk for osteosarcoma, such as those with Paget's disease of
 bone or unexplained elevations of alkaline phosphatase, hereditary disorders
 predisposing to osteosarcoma, or with a prior history of external beam or implant
 radiation involving the skeleton.

 16. Patients with skeletal malignancies or bone metastases.

 17. Pregnancy or suspected pregnancy or lactating. Female patients of childbearing
 potential must have a negative pregnancy test at screening and be willing and able to
 use two medically acceptable methods of birth control (reliable use of oral
 contraceptive with physical barrier, non-hormonal intrauterine device with condom,
 diaphragm with condom, or condom with spermicide) from the screening visit through 90
 days from last dose or declare that they are abstaining from sexual intercourse from
 the screening visit through the study termination visit or are surgically sterile
 (have undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or
 postmenopausal. True abstinence can only be in line with the preferred and usual
 lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
 symptothermal, and postovulation methods), declaration of abstinence for the duration
 of a study, and withdrawal are not acceptable methods of contraception.

 Childbearing potential is defined as those who are not surgically sterile (i.e., bilateral
 tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal. Women
 will be defined as postmenopausal if they have been amenorrheic for 12 months (prior to
 signature of Informed Consent Form) without an alternative medical cause.