Autosomal Dominant Hypocalcemia Type 1 is a rare genetic form of hypoparathyroidism. Autosomal Dominant Hypocalcemia (ADH) Type 1 may be passed down from affected parents to their children.~This is a multi-center, randomized, open-label, two-arm, three-period Phase 3 study with a Long-Term Extension (LTE) evaluating the efficacy and safety of encaleret in participants with ADH1. The study will be conducted in adolescents and adults (≥16 years). Approximately 60 eligible ADH1 participants who are naïve to encaleret will enroll in this study.~The main portion of the study is divided into a Screening Period and 3 Periods followed by an optional Long-Term Extension. The estimated duration of this main portion of the study is approximately 12 months. The duration of the long-term extension is approximately 48 months.~Participants will enter an up-to-6-week Screening period and once confirmation of all Inclusion/Exclusion criteria transition into an up-to-15-week standard of care (SoC) optimization phase in which each participant's SoC treatment regimen will be assessed and optimized by Investigators in relation to the presence/absence and control of hypocalcemia-related symptoms and the observed blood and 24-hr urine calcium values. The eligible participants will enter Period 1 after completing the SoC optimization phase.~Period 1 is the 4-week SoC Maintenance period of the study during which the SoC dose will only be adjusted to address potential safety concerns such as hypocalcemia or hypercalcemia.~After completion of Period 1, eligible participants will be randomized 2:1 to the encaleret treatment arm or the SoC treatment arm and will enter Period 2, a 20-week dose titration period. Both the investigator and participant will know whether the participant was randomized to the encaleret treatment arm or SoC treatment arm. During Period 2, encaleret or SoC will be titrated/adjusted as needed in an effort to achieve target blood calcium levels while minimizing urine calcium excretion.~After completion of Period 2, participants will proceed to Period 3, the 4-week dose maintenance period. During Period 3, encaleret or SoC doses should remain stable. Doses will only be titrated/adjusted to address potential safety concerns including management of hypocalcemia or hypercalcemia.~Following completion of Period 3, participants may enter a Long-Term Extension and receive encaleret treatment for approximately 48 months, or until a participant has access to commercial encaleret, or the Sponsor decides to end the study, whichever occurs first.
A global, multi-center, Phase 3, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Encaleret Compared to Standard of Care in Participants with Autosomal Dominant Hypocalcemia Type 1 (ADH1)