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document
Pharmacodynamic effects on biochemical markers of bone turnover and pharmacokinetics of the cathepsin K inhibitor , ONO-5334 , in an ascending multiple-dose , phase 1 study . Selective inhibitors of cathepsin K , which has a major role in the degradation of bone collagen , are potential new treatments for osteoporosis . The pharmacokinetics and the pharmacodynamic effects on biochemical markers of bone turnover of the new cathepsin K inhibitor , ONO-5334 , were investigated in a multiple ascending dose , phase 1 study . A total of 120 healthy postmenopausal women were enrolled , and doses of 10 to 600 mg once daily and 50 and 300 mg twice daily were evaluated in 15- and 28-day multiple-dosing cohorts . Plasma ONO-5334 concentration reached steady state within 2 days . Twenty-four hours after the last dose in the 15-day multiple-dose cohort , 100 , 300 , and 600 mg once daily reduced urinary C-terminal telopeptide of type I collagen by a mean ( ± standard deviation ) 44.9 % ± 13.6 % , 84.5 % ± 4.4 % , and 92.5 % ± 1.3 % , respectively . The 28-day cohort showed similar effects . There were far smaller effects on bone-specific alkaline phosphatase ( B-ALP ) , tartrate-resistant acid phosphatase 5b ( TRAP5b ) , or osteocalcin ( OC ) ( measured after 28 days ) . ONO-5334 was well tolerated up to 600 mg/d and for up to 28 days of multiple dosing . Multiple dosing with ONO-5334 100 mg resulted in considerable suppression of bone resorption markers with no appreciable effects on bone formation markers ( B-ALP , OC ) or osteoclast number ( TRAP5b ) .
50863
Intervention_Pharmacological
cathepsin K inhibitor , ONO-5334
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Intervention_Pharmacological
cathepsin K inhibitor , ONO-5334
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Outcome_Physical
biochemical markers of bone turnover
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Outcome_Physical
pharmacokinetics
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Outcome_Physical
pharmacokinetics and the pharmacodynamic effects on biochemical markers of bone turnover
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Outcome_Physical
urinary C-terminal telopeptide of type I collagen
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Participant_Condition
postmenopausal
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Participant_Sex
women