Safety, Tolerability, and Clinical Effects of Twice-daily Doses of Cinacalcet (AMG 073) in Adults With Primary Hyperparathyroidism (HPT)

Inclusion criteria

• Men or women ≥ 18 years old before beginning of screening
• Use, in the opinion of the principal investigator, effective contraceptive measures throughout the study
• Negative serum pregnancy test within 15 days before day 0
• Plasma iPTH concentration > 45 pg/mL on at least 2 occasions (during the screening phase) at least 7 days apart
• Serum calcium concentration ≥ 11 mg/dL on 2 occasions (during the screening phase) at least 7 days apart
• Acceptable renal function, with an estimated creatinine clearance > 50 mL/min as determined by the Cockroft and Gault equation
• Acceptable hepatic function, defined as serum aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin ≤ 2 times the upper limit of normal (central laboratory's range)
• Laboratory test results within the central laboratory's normal range for hematology, coagulation, urinalysis, and clinical chemistry parameters not mentioned specifically in other inclusion/exclusion criteria
• Chest x-ray within the past 12 months, with no evidence of an active infectious, inflammatory, or malignant process
• Informed consent for participation in the study

Exclusion criteria

• Any unstable medical condition requiring hospitalization within 30 days before day 0, or otherwise unstable condition in the judgment of the investigator
• Awaiting or scheduled for parathyroidectomy within 2 months after study day 0
• Pregnant or nursing
• Received, within 21 days before day 0, therapy with systemic glucocorticoids (> 5 mg/day prednisone or equivalent), lithium, tricyclic antidepressants (with the exception of amitriptyline and nortriptyline), thioridazine, haloperidol, flecainide, drugs with a narrow therapeutic index that are primarily metabolized by hepatic cytochrome P450 CYP 2D6, drugs that affect renal tubular calcium handling (ie, thiazide or loop diuretics), or calcitonin
• Dose changes in bisphosphonates, thyroid replacement therapy, selective estrogen receptor modulators (SERMs), or changes in daily doses of estrogen (greater than 0.75 mg) within 90 days before day 0
• Subjects who discontinued estrogen or SERM therapy must have been off treatment for at least 90 days before day 0.
• Alcohol or illicit drug abuse within 12 months before day 0 based on self-report
• Myocardial infarction within 6 months before day 0
• Ventricular rhythm disturbance requiring current treatment
• Seizure within 12 months before day 0
• History (within 5 years) of malignancy of any type, other than nonmelanomatous skin cancers or in situ cervical cancer
• Evidence (within 5 years) of treatment for and/or active sarcoidosis, tuberculosis, or diseases other than primary HPT known to cause hypercalcemia
• History of familial hypocalciuric hypercalcemia (FHH)
• Uncontrolled diabetes, as defined by hemoglobin A1c (HbA1c) ≥ 8.0
• Gastrointestinal disorder that may be associated with impaired absorption of orally administered medications
• Inability to swallow tablets similar in size to an aspirin tablet
• Known sensitivity to products administered during the study
• Previous participation as a subject in this study (ie, withdrawn early) or a prior study involving AMG 073 administration
• Enrolled in, or not yet completed at least 28 days since ending other investigational device or drug trial(s)
• Psychiatric disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements
• Any other condition that might reduce the chance of obtaining data (ie, known poor compliance) required by the protocol or that might compromise the ability to give truly informed consent