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).


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 5h 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<0.0001; P=0.007]. 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.
Karsdal
M A
MA
Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. mk@nordicbioscience.com
Byrjalsen
I
I
Henriksen
K
K
Riis
B J
BJ
Lau
E M
EM
Arnold
M
M
Christiansen
C
C
D000284:Administration, Oral; D000368:Aged; D019540:Area Under Curve; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism*; D002116:Calcitonin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002352:Carrier Proteins / Q000627:therapeutic use*; D024042:Collagen Type I; D024043:Collagen Type II / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000097:blood / Q000652:urine; D010455:Peptides; D011347:Procollagen / Q000097:blood
D050071:Bone Density Conservation Agents; D002352:Carrier Proteins; D024042:Collagen Type I; D024043:Collagen Type II; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; C028815:salmon calcitonin; D002116:Calcitonin