The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study

Background The aim of this study was to investigate the pharmacokinetic and pharmacodynamic parameters of oral salmon calcitonin (oSCT) administered over 14 days to men and women presenting with osteoarthritis (OA) Materials and methods The study was a phase-I, 2-week, placebo-controlled, double-blind, double-dummy, randomized, gender-stratified study including 73 subjects aged 57--75 years Patients had painful OA with a Kellgren and Lawrence index score of I-III Treatment allocations were, 0 6 mg, 0 8 mg of oSCT, or placebo Treatment was given twice daily for 14 days The morning dose was administered between 07 00 and 08 00 at least 30 min before breakfast The second dose was administered 30 min before evening dinner On treatment day 1 and 14, the morning dose was followed by 5 h of fasting, and blood samples and urine were collected immediately prior to dosing and according to the protocol Study parameters were plasma sCT levels, bone resorption by CTX-I (serum C-terminal telopeptide of collagen type I), bone formation by osteocalcin (serum OC), and cartilage degradation by CTX-II (urine C-terminal telopeptide of collagen type II) (clinicaltrials gov identifier NCT00486369) Results Doses of 0 8 mg compared with 0 6 mg produced significantly higher C-max and AUC(0-4 hrs), of calcitonin, P = 0 03 This resulted in significant reductions in CTX-I and CTX-II, [P < 00001. P = 0007] No differences were observed between baseline and follow-up at day 14 in pharmacokinetic and pharmacodynamic parameters Gender had no observable influence on results Conclusions oSCT given twice daily with a pre-dinner and morning fasting dosing resulted in reductions in markers of bone resorption and cartilage degradation (C) 2009 Osteoarthritis Research Society International Published by Elsevier Ltd All rights reserved