Bone turnover markers and pharmacokinetics of a new sustained-release formulation of the cathepsin K inhibitor, ONO-5334, in healthy post-menopausal women.
J Bone Miner Metab
; 33(1): 93-100, 2015 Jan.
Article
in En
| MEDLINE
| ID: mdl-24458199
ABSTRACT
A sustained-release tablet (SRT) of ONO-5334 was compared to the immediate-release tablet (IRT) dose, which demonstrated effects on bone mineral density (BMD) comparable to those of therapy with alendronate. The single-dose phase was a randomized, partial single-blind, crossover study where 50-, 100-, and 300-mg SRTs and 300-mg IRTs were administered to nine post-menopausal women. The multiple-dose phase was a randomized, double-blind, placebo-controlled, parallel-group study where 100- and 300-mg SRTs, or placebo were administered to 24 women. After a single administration of a 300-mg SRT, mean C max was 3.3-fold lower, mean AUCinf was 0.83-fold lower and mean C 24h was 5.4-fold higher compared to the 300-mg IRT. Repeated SRT dosing did not significantly affect PK, although C 24h increased slightly. After a single ONO-5334 dose, serum CTX-I was suppressed by ~50 % within 1 h, reaching maximum suppression 6 h post-dose. Greater suppression was maintained longer by the 300-mg SRT vs. the 300-mg IRT. Second morning void and cumulative urine CTX-I showed clear dose-response effects at/over 24 h for SRT, with maximum suppression occurring at/over 24 h (except 50- and 300-mg cumulative urine). Repeated dosing suggested greater suppression of urine CTX-I. Compared with the IRT, the SRT showed reduced C max, greater C 24h, and slightly reduced AUCinf dose for dose. The SRT showed clear dose-response suppression on bone resorption and greater efficacy dose for dose vs. the IRT.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoporosis
/
Bone and Bones
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Delayed-Action Preparations
/
Thiazolidines
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Cathepsin K
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Aged
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Female
/
Humans
/
Middle aged
Language:
En
Journal:
J Bone Miner Metab
Journal subject:
METABOLISMO
Year:
2015
Type:
Article