A Phase 3 Randomized Clinical Trial to Investigate the Safety and Efficacy of Palopegteriparatide at Doses Greater Than 30 μg/Day in Adult Participants With Hypoparathyroidism

Exclusion Criteria

• •1. Impaired responsiveness to PTH (pseudohypoparathyroidism), which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia
• •2. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than HP
• •3. Use of loop diuretics, phosphate binders (other than calcium supplements), digoxin, lithium, methotrexate, biotin \>30 µg/day, or systemic corticosteroids (other than as replacement therapy)
• •4. Use of thiazide diuretic within 4 weeks prior to the 24-hour urine collection scheduled to occur within 1 week prior to Visit 1
• •5. Use of PTH-like drugs other than palopegteriparatide (whether commercially available or through participation in an investigational trial), including PTH(1-34), or other N-terminal fragments, analogs of PTH or PTH-related protein, or PTH1R biased agonists within 4 weeks prior to Screening
• •6. Use of drugs known to influence calcium and bone metabolism within 12 weeks prior to Screening
• •7. Use of osteoporosis therapies other than bisphosponate known to influence calcium and bone metabolism within 2 years prior to Screening. Note: use of bisphosphonate (oral or intravenous \[IV\] is not exclusionary
• •8. Non-hypocalcemic seizure disorder with occurrence of a seizure within 26 weeks prior to Screening.
• •9. Increased risk for osteosarcoma
• •10. Women who are pregnant, intend to become pregnant, or are lactating
• •11. Male who has a female partner who intends to become pregnant or is of childbearing potential and is unwilling to use adequate contraceptive methods during the trial
• •12. Diagnosed drug or alcohol dependence within 3 years prior to Screening
• •13. Chronic or severe cardiac disease within 26 weeks prior to Screening
• •14. Cerebrovascular accident within 5 years prior to Screening.
• •15. Within 26 weeks prior to Screening: acute colic due to nephrolithiasis, or acute gout
• •16. Participation in any other interventional trial in which receipt of investigational drug or device other than palopegteriparatide occurred within 8 weeks (or within 5.5 times the half-life of the investigational drug) (whichever comes first) prior to Screening.
• •17. Known allergy or sensitivity to PTH or any of the excipients \[metacresol, mannitol, succinic acid, NaOH/(HCl)\] of the investigational product