Study of the PTH-independent Effects of Encaleret on Mineral Homeostasis in Subjects With Postsurgical Hypoparathyroidism (PSH)

INCLUSION CRITERIA: Participants must meet the following criteria for inclusion during screening: Be able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. Age >= 18 years Postmenopausal women are allowed to participate in this study: a. Women are considered postmenopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to start of the study. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, shall she be considered not of childbearing potential. Body mass index (BMI) >= 18.5 to < 39 kg/m2 Have a diagnosis of PSH, either permanent PSH (Cohort 1, surgery >= 12 months ago) or recent PSH (Cohort 2, surgery < 12 months ago). Participants must have achieved a fasting albumin-corrected blood calcium level of 7.8-10.2 mg/dL on conventional therapy without significant symptoms of hypocalcemia or hypercalcemia at baseline. Participants being treated with thiazide diuretics may be enrolled if they are willing and able to discontinue thiazides for at least 5 half-lives prior to initiation of encaleret and remain off during the study treatment period. (5 half-lives of hydrochlorothiazide = 75 hours; chlorothiazide = 10 hours; chlorthalidone = 12.5 days). If the thiazide is being used as an antihypertensive, as opposed to use as a urine calcium-lowering drug, alternative therapy will be offered. Participants being treated with strong CYP3A4 inhibitors (including clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) may be enrolled if they are willing and able to discontinue these medications for at least 5 half-lives prior to initiation of encaleret and remain off during the study treatment period. Participants being treated with magnesium or potassium citrate supplements should discontinue such treatment starting on Day -2. Participants being treated with medications that have impacts on mineral metabolism which investigators believe may impact study endpoints may be enrolled if they are willing and safely able to discontinue the medication for at least 5 half-lives prior to initiation of encaleret and remain off during the study treatment period. Participants must have Thyroid-Stimulating Hormone (TSH) in the normal range prior to being eligible to continue to the treatment phase of the study. Participants who are being treated with thyroid replacement therapy will be allowed to enroll as long as TSH is normal range. Participants who require TSH suppression for thyroid cancer treatment are not eligible for this study. EXCLUSION CRITERIA: Participants who meet any of the following criteria during Screening will not be eligible to participate in the study: History of treatment with any PTH analog (i.e., PTH 1-84, PTH 1-34, TransCon PTH, etc.) within the previous 3 months History of prior treatment with encaleret History of hypocalcemic seizure within the past 3 months Blood 25-OH Vitamin D level < 25 ng/mL a. If subject has a blood 25-OH Vitamin D level < 25 ng/mL at the screening visit, they will be prescribed cholecalciferol or ergocalciferol supplementation. Once the 25-OH Vitamin D level is > 25 ng/mL, the subject will be eligible to continue to the treatment phase of the study. Participants with hemoglobin (Hgb) < 13 g/dL for men and < 12 g/dL for women a. If subject has a low Hgb at the screening visit due to iron, B12, or folate deficiency, they will be prescribed supplementation. Once the Hgb level is > 13 in men or > 12 in women, the subject will be eligible to continue to the treatment phase of the study. Abnormal laboratory values which in the opinion of the investigator, would make the subject not suitable for participation in the study Estimated glomerular filtration rate (eGFR) < 50 mL/minute/1.73 m2 using CKD-EPI. Insufficient hepatic function defined as one of the following: Total Bilirubin > 1.5 x ULN OR Aspartate transaminase (AST) > 2x ULN OR Alanine transaminase (ALT) > 2x ULN 12-lead resting electrocardiogram (ECG) with clinically significant abnormalities. Participants with baseline QTcF (using the Frederica equation) > 450 milliseconds (ms) will not be eligible for the treatment phase of the study. Clinically significant cardiac disease including any of the following: Congestive heart failure requiring treatment (NY Heart Association grade >= 2) - History of clinically significant cardiac arrythmias including ventricular arrhythmias, atrial fibrillation, or conduction abnormalities History of unstable angina pectoris or acute myocardial infarction Participants with positive hepatitis B surface antigen (HBsAg) or Hepatitis A immunoglobulin M (IgM) at the Screening Visit. Participants who are in complete remission from Hepatitis C as evidence by sensitive assay >=12 weeks after completion of HCV therapy are allowed to participate in the study. Participants with human immunodeficiency virus (HIV) infection on a stable dose of anti-retroviral therapy who have an undetectable viral load are allowed to participate in the study. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum hCG laboratory test Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months following the discontinuation of study treatment. Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. Male sterilization (at least 6 months prior to screening). For female participants on the study the vasectomized male partner should be the sole partner for that subject. Combination of the following (a+c or b+c): Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS) Barrier method of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Sexually active male participants who are unwilling to use a condom during vaginal intercourse while taking the encaleret (study drug) and for 3 months after the last dose of the study drug. Participants should not father a child during active participation in the study starting with the first encaleret dose. Condoms are not required if the subject is vasectomized or if the subject s partner is not a woman of child-bearing potential. Hypersensitivity to any active substance or excipient of encaleret History of drug or alcohol dependency within 12 months preceding the Screening Visit Current participation in other investigational drug studies Unwillingness to refrain from blood donation within 12 weeks prior to admission visit through one year after the last dose of the study drug. If subject donated blood within 12 weeks of the screening visit, they will need to wait until 12 weeks have passed since blood donation for the admission visit. Participants who have a history of diseases of mineral metabolism other than hypoparathyroidism or hyperparathyroidism which investigators believe may impact study endpoints (for example, X-linked hypophosphatemia, rickets, etc).