A Study to Assess the Efficacy and Safety of Twice-Daily Dose Regimens of an Oral Calcimimetic Agent AMG 073 (Cinacalcet) in Primary Hyperparathyroidism (PHPT)

A Double-Blind, Randomized, Placebo-Controlled, Multicenter Dose-Titration Study to Assess the Efficacy and Safety of Twice-Daily Dose Regimens of an Oral Calcimimetic Agent AMG 073 (Cinacalcet) in Primary Hyperparathyroidism (PHPT)

This randomized, placebo-controlled study in patients with primary HPT was designed to evaluate the efficacy, safety, pharmacokinetics, and health-related quality of life (HRQOL) of AMG 073 when administered 2 times a day (BID). The study consisted of 3 phases: a 12-week dose-titration phase, a 12-week maintenance phase, and a 28-week follow-up phase.

Inclusion Criteria:

• Men or women ≥ 18 years of age at screening
• Using, in the opinion of the principal investigator, effective contraceptive measures
• Plasma iPTH concentration > 45 pg/mL on at least 2 occasions at least 7 days apart during the 12 months preceding day 0 (at least 1 of these determinations should have been made during screening by the central lab) and serum calcium concentration > 10.3 mg/dL and ≤ 12.5 mg/dL on at least 2 occasions 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 aminotransferase, alanine aminotansferase, and total bilirubin ≤ 2 times the upper limit of normal according to the range provided by the central laboratory
• Laboratory test results within the central laboratory's normal range for hematology, urinalysis, and clinical chemistry parameters not mentioned specifically in other inclusion and exclusion criteria
• Chest x-ray within the previous 12 months without evidence of an active infectious, inflammatory, or malignant process
• Subject or legally acceptable representative gave informed consent for participation in the study

Exclusion Criteria:

• Unstable medical condition, defined as having been hospitalized within 30 days before day 0
• Pregnant or nursing
• Body habitus that precluded accurate DXA measurements
• Therapy within 21 days before day 0 with systemic glucocorticoids, lithium, tricyclic antidepressants with the exception of amitriptyline and nortryptiline, thioridazine, haloperidol, flecainide or other drugs with a narrow therapeutic index that are primarily metabolized by hepatic cytochrome P450 (CYP) 2D6, drugs that affect renal tubular calcium handling (eg, thiazide or loop diuretics), or calcitonin
• Received, within 90 days before day 0, therapy with bisphosphonates, with fluoride, or changes in thyroid replacement therapy
• Dose changes in selective estrogen receptor modulators (SERMs), or significant changes in doses of estrogen within 90 days before day 0. If a subject had discontinued estrogen or SERM therapy, they must have been off treatment for at least 90 days before day 0
• Alcohol abuse, or use of illicit drugs, within 12 months before day 0
• Myocardial infarction (MI) within 6 months before day 0
• Ventricular rhythm disturbance requiring current treatment
• Seizures 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
• Within the past 5 years, evidence of treatment for and/or active sarcoidosis, tuberculosis, or other diseases known to cause hypercalcemia
• History of familial hypocalciuric hypercalcemia (FHH)
• Uncontrolled diabetes, as defined by hemoglobin A1c (HbA1c) ≥ 8.0
• Gastrointestinal disorder that might have been associated with impaired absorption of orally dministered medications
• Inability to swallow tablets
• Known sensitivity to any of the products to be administered during the study
• Psychiatric disorder that would have interfered with understanding and giving informed consent or compliance with protocol requirements
• Other condition that might have reduced the chance of obtaining data (eg, known poor compliance) required by the protocol or that might have compromised the ability to give truly informed consent