PTH-independent Effects of Encaleret

• 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 = 12 months ago) or recent PSH (Cohort 2, surgery 60 ng/mL
• If subject has a blood 25-OH Vitamin D level = 25 ng/mL, the subject will be eligible to continue to the treatment phase of the study.
• If a subject has a blood 25-OH Vitamin D level >60 ng/mL at the screening visit, their vitamin D supplementation will be adjusted. Once the 25-OH Vitamin D level is 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 screening QTcF (using the Fridericia equation) > 450 milliseconds (ms) will not be eligible for the treatment phase of the study.
• If a participant has a prolonged QTcF during screening due to a reversible cause of long QT (for example hypocalcemia or QT-prolonging medications), the subject may be eligible for the treatment phase of the study if the reversible cause can be addressed, and repeat ECG shows QTcF = 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 (HCV) 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 human chorionic gonadotropin (hCG) laboratory test
• Clinically significant abnormalities in thyroid function tests. This does not include participants with non-clinically significant or treated thyroid diseases (e.g. subclinical hypothyroidism, hypothyroidism on treatment, etc.). Participants on thyroid-stimulating hormone (TSH)-suppression therapy for thyroid cancer are allowed to participate in this study regardless of TSH level.
• 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 three (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, sympto-thermal, post-ovulation 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 sta