Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin

The study was a randomized, double-blind, double-dummy, placebo-controlled, phase I study to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral sCT in healthy postmenopausal women. Totally 81 subjects were included, aimed at investigation of a morning dose given at 8:00 (n = 42), a pre-dinner dose given at 17:00 (n = 20), and an evening dose given at 22:00 (n = 19). Plasma sCT concentrations and bone resorption (C-terminal-telopeptide of collagen type I (CTX-I)) was assessed.Morning and pre-dinner dosing led to comparable concentration of sCT of 45 pg/ml, whereas there was a tendency towards lower Cmax for the evening dosing having a mean of 24 pg/ml. The maximum difference from placebo was observed 1 to 3 hours post-dose with a 40 to 50% suppression consequent to morning dose, and about 75% suppression after pre-dinner and evening dose, due to the increase bone resorption as a result of circadian variation.The study suggests that orally administered 0.8 mg of salmon calcitonin was effective in suppression of serum CTX irrespective of time of dosing. The pre-dinner dosing resulted in optimum efficacy response corresponding to an overall suppression of bone resorption by 25%.NCT00411125Calcitonin (CT) is a 32 amino-acid hormone produced by parafollicular cells (C-cells) in the thyroid gland [1], secreted in response to excess calcium in the serum [2]. Binding of calcitonin to the calcitonin receptor on osteoclasts results in a reduction in a raid bone resorption [3-5]. Salmon calcitonin is among to most potent calcitonins, and belongs to the teleost/avian family[1]. Salmon calcitonin (sCT) is approved for the treatment of osteoporosis and other diseases involving accelerated bone turnover [6,7]. Preliminary evidence suggests that calcitonin may be a potential treatment for osteoarthritis that also entails increased osteoclast function [8-10].Calcitonin treatment has until now been limited to either subcutaneous or intranasal calcitoni