Efficacy, Safety, and Tolerability of Encaleret in Participants With Chronic Hypoparathyroidism

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study With an Open-Label Extension Investigating Efficacy, Safety, and Tolerability of Encaleret in Participants With Chronic Hypoparathyroidism

The aim of the study is to evaluate the efficacy, safety, and tolerability of orally administered encaleret tablets in participants with chronic hypoparathyroidism (HP).

Key Inclusion Criteria:

• Participants must have had a clinically confirmed diagnosis of chronic HP, with disease duration of at least 26 weeks prior to screening. Cause of chronic HP can be postsurgical, autoimmune or idiopathic.
• For participants with nonsurgical chronic HP etiology, sufficient documentation that the participant does not harbor any variants in calcium-sensing receptor (CASR) or GNA11 that are classified as pathogenic, likely pathogenic, or of uncertain significance, with the exception of benign common polymorphisms (CASR A986S and R990G) is needed.
• Participants must be on stable doses of calcium and active vitamin D supplementation at or above the following minimum thresholds for at least 6 weeks prior to screening.

For participants enrolled in study sites outside Japan:

1. Calcitriol ≥0.5 micrograms (μg)/day or alfacalcidol ≥1.0 μg/day

2. Elemental calcium ≥800 milligrams (mg)/day (for example, calcium citrate, calcium carbonate)

   • Participants must meet the following criteria during screening: cCa within 7.8 to 9.5 mg/deciliter (dL) and 24-hour UCa ≥300 mg/day (males) or ≥250 mg/day (females).
   • Participants have serum 25-hydroxy (OH) vitamin D concentration of 20 to 80 nanograms (ng)/milliliter (mL) (50-200 nanomoles [nmol]/liter [L]).
   • Participants have serum magnesium concentration within the reference range.
   • Participants on thiazide or loop diuretics must be able to discontinue them during the first 24 weeks of study (treatment).
   • Participants must be capable of giving signed informed consent or assent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.

Key Exclusion Criteria:

• Genetically confirmed diagnosis of autosomal dominant hypocalcemia type 1 (ADH1) or autosomal dominant hypocalcemia type 2 (ADH2) due to activating variants in CASR or GNA11, respectively.
• History of hypocalcemic seizure in the 3 months prior to screening.
• History of cancer (except non-melanoma skin cancer) or bone metastases in the 5 years prior to screening.
• Prior skeletal irradiation, chemotherapy with alkylating agents, or diagnosis of Paget's disease, fibrous dysplasia, chronic osteomyelitis, bone infarcts, benign bone tumors with curettage and grafting, retinoblastoma, or Li-Fraumeni syndrome.
• Presence or history of any disease or condition (for example, drug or alcohol dependence) that, in the view of the investigator, would affect the participant's safety or places the participant at high risk of poor treatment compliance or of not completing the study.

Other protocol-defined inclusion/exclusion criteria apply.