Safety, Pharmacokinetics and Efficacy of MBX 2109 in Patients With Hypoparathyroidism

Exclusion Criteria

• •1. Has a known history of pseudohypoparathyroidism (impaired responsiveness to PTH, which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia).
• •2. Has any disease (other than hypoparathyroidism) that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels (e.g., disorders of the calcium sensing receptor \[e.g., autosomal dominant hypocalcemia type 1\] are exclusionary).
• •3. Use any of the following therapies:
• •1. Loop diuretics, thiazide diuretics, phosphate binders (other than calcium carbonate or citrate), digoxin, lithium, methotrexate, raloxifene hydrocholoride, or acute systemic corticosteroids within 4 weeks prior to the Screening Visit;
• •* Chronic systemic corticosteroid use is allowed if the dose has been stable for 4 weeks prior to Screening visit
• •2. PTH or PTH-related protein drugs such as PTH(1-84) and PTH(1-34) within 4 weeks of the Screening visit;
• •3. Oral or intravenous bisphosphonates, denosumab, or romosozumab-aqqg within 18 months of the Screening visit; or
• •4. Other drugs known to influence calcium and bone metabolism such as calcitonin, fluoride tablets (\>0.5 mg per day), strontium or cinacalcet hydrochloride within 3 months of the Screening visit.
• •4. Had a non-hypocalcemic seizure within 6 months of the Screening visit. Note: a history of seizures that occur in the setting of hypocalcemia is not exclusionary
• •5. Is at an increased risk for osteosarcoma (e.g., Paget's disease, prior history of substantial external beam or implant radiation therapy involving the skeleton, unexplained elevations of alkaline phosphatase)
• •6. Is affected by active or uncontrolled disease processes that may adversely affect gastrointestinal absorption at the discretion of the PI.
• •7. Has a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than differentiated thyroid cancer, basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 2 years from the Screening visit.
• •8. Has any clinically significant cardiovascular disease within 6 months prior to the Screening visit such as symptomatic heart failure, an acute coronary syndrome, uncontrolled arrhythmia, or cerebrovascular accident.
• •9. Has a clinically significant abnormal 12-lead ECG in the opinion of the investigator at the Screening visit suggestive of underlying cardiac disease.
• •10. Has a seated systolic blood pressure \<100 mmHg or \>165 mmHg and/or diastolic blood pressure \>100 mmHg at the Screening visit. If outside this range, measurement can be repeated on another day for eligibility purposes within the Screening Period. If on medications for hypertension, the doses should be stable for 4 weeks prior to the Screening visit.
• •11. Has a history of symptomatic nephrolithiasis within 3 months of the Screening visit.
• •12. Has an episode of acute gout within 2 months of the Screening visit.
• •13. Has any major surgery performed within the 6 months prior to the Screening visit or plans to have surgical procedures that might interfere with the patient's ability to complete the study.
• •14. Is pregnant, lactating or a woman of childbearing potential (WOCBP) who plans to conceive during the study.
• •1. WOCBP must use at least 2 highly effective methods of contraception throughout the study and for 6 weeks following administration of the last dose of study drug.
• •2. A heterosexually active male patient and his female partner(s) of childbearing potential must agree to use 2 effective birth control methods for the duration of the study and for 90 days after the last dose of study drug. A male patient must agree to refrain from sperm donation from the date of screening until 90 days after his last dose of study drug.
• •15. Has any disease or condition that, in the opinion of the investigator, may make the patient unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
• •16. Has a known allergy or sensitivity to PTH or any of the excipients used in MBX 2109.
• •17. Has a diagnosis of drug or alcohol dependence within 12 months prior to the Screening visit.
• •18. Has participated in any other interventional trial in which the patient received an investigational drug within 2 months or within 5 half-lives of the investigational drug (whichever is the longest) prior to the Screening visit.
• •19. Has any other reason that, in the opinion of the investigator, would prevent the patient from completing participation or following the study schedule.