Cinacalcet HCl reduces iPTH, serum calcium, serum phosphorus, and the calcium-phosphorus product in patients with chronic kidney disease and secondary hyperparathyroidism who are receiving dialysis, and reduces elevated serum calcium associated with primary hyperparathyroidism and parathyroid carcinoma. Cinacalcet is administered orally, and thus concomitant administration with food may affect its bioavailability. The objective of this study was to examine the effect of fat and caloric intake on cinacalcet exposure. This phase 1, randomized, open-label, single-dose, 3-period, 3-treatment, 6-sequence crossover study enrolled 30 healthy subjects (19 men, 11 women) to receive a single oral dose of cinacalcet HCl (Sensipar®/Mimpara®; Amgen Inc. Thousand Oaks, CA) (90 mg) on 3 separate occasions: following a high-fat, high-caloric meal, a low-fat, low-caloric meal, and a 10-hour fast. Blood samples were obtained predose and up to 72 hours postdose for pharmacokinetic (AUC∞, Cmax) and safety evaluations. Twenty-nine subjects completed all the 3 treatment conditions. The mean (90% confidence intervals) AUC∞ following high- and low-fat meals was increased by 68 (48 to 89)% and 50 (33 to 70)%, respectively, relative to fasting. The difference in mean AUC∞ between high- and low-fat meals was small [12 (9.9-26)%]. The mean tmax of cinacalcet was prolonged in fasting subjects (6 h) in relation to high-fat (4 h) and low-fat (3.5 h) fed subjects. The mean t1/2β was similar between treatment conditions. Adverse events (AE) were observed at a similar frequency across the treatment conditions [high fat (34%), low fat (23%), and fasting (31%)]; the type of AE did not differ among the treatment conditions. The most common treatment-related AEs were headache 6/30 (20%), nausea 5/30 (17%), and dyspepsia 4/30 (13%) subjects. Administration of cinacalcet with either high- or low-fat meals results in significant increases in exposure, relative to administration under fasting conditions. However, the small differences observed in exposure following the ingestion of the different types of meals suggest that although food has a significant effect, the type of food does not. The observed effect supports the labeling statement that cinacalcet be taken with food, or shortly after a meal.
From the Departments of 1Early Development/Medical Sciences; 2Biostatistics; and 3Pharmacokinetics and Drug Metabolism, Amgen Inc. Thousand Oaks, CA 91320.
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