Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1

Key Inclusion Criteria:

• Participants must have a documented pathogenic or likely pathogenic activating variant, or variant of uncertain significance, of the calcium sensing receptor (CASR) gene associated with biochemical findings of hypoparathyroidism.
• Participants must have a documented history of symptoms or signs of ADH1.
• Participants 16 to <18 years old must have closed growth plates on hand radiograph.
• Participants treated with thiazide diuretics must discontinue thiazides for at least 14 days prior to SoC Optimization Visit 1 through Week 24 (Period 3). When the thiazide is being used as an antihypertensive, alternative therapy will be prescribed by the Investigator as needed.
• Participants treated with phosphate binders (other than calcium salts) must discontinue the phosphate binders at least one day prior to the SoC Optimization Visit 1.
• Participants treated with magnesium or potassium supplements must be willing to discontinue such treatment prior to the first dose of encaleret.
• Participants treated with potassium-sparing diuretics must be willing to discontinue such treatment prior to the first dose of encaleret.
• Participants must meet SoC Optimization criteria as defined in the protocol.

Key Exclusion Criteria:

• History of hypocalcemic seizure within the past 3 months preceding Screening.
• History of thyroid or parathyroid surgery.
• History of renal transplantation.
• Pregnant or nursing (lactating) women, where pregnancy is confirmed by a positive beta-human chorionic gonadotropin (β-hCG) laboratory test.
• History of treatment with parathyroid hormone (PTH) 1-84 or 1-34 within the 2 months preceding Screening and requiring SoC doses exceeding >1.2× their pre-PTH treatment total daily doses or bone turnover markers, Collagen cross-linked C-telopeptide (CTx )and Procollagen type 1 N-propeptide (P1NP), > upper limit of normal for sex, age (men only) and menopausal status (women only).
• Blood 25-OH Vitamin D level <25 nanograms (ng)/milliliter (mL).
• Estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m^2 using chronic kidney disease-EPI creatinine equation refit without the race variable (chronic kidney disease-EPI creatinine equation refit without the race variable [CKD-EPIcr_R]) (for participants <18 years old the Bedside Schwartz equation should be used).
• Participants with positive Hepatitis B surface antigen (HBsAg), Hepatitis A immunoglobulin M (IgM), or human immunodeficiency virus (HIV) viral serology test at the Screening Visit. Participants who are in complete remission from Hepatitis C virus (HCV) as evidenced by sensitive assay ≥12 weeks after completion of HCV therapy may participate in the study.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.