Trial reportBMC musculoskeletal disorders2017
Antiresorptive effect of a cathepsin K inhibitor ONO-5334 and its relationship to BMD increase in a phase II trial for postmenopausal osteoporosis.
Trial report in BMC musculoskeletal disorders, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- Bidirectional crosstalk between the bone extracellular matrix and lysosomes in bone remodeling and osteoporosis.Frontiers in endocrinology · 2025Review
- Proteases and Osteoporosis: A Comprehensive Review of Their Role in Bone Health.Current drug targets · 2025Review
- Therapeutic Treatments for Osteoporosis-Which Combination of Pills Is the Best among the Bad?International journal of molecular sciences · 2022Review
- Cathepsin KFrontiers in cell and developmental biology · 2022Review
- Bone Quality in Chronic Kidney Disease Patients: Current Concepts and Future Directions - Part II.Kidney diseases (Basel, Switzerland) · 2021Review
- The Mechanosensory Role of Osteocytes and Implications for Bone Health and Disease States.Frontiers in cell and developmental biology · 2021Review
- Reassessing enzyme kinetics: Considering protease-as-substrate interactions in proteolytic networks.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cathepsin K: The Action in and Beyond Bone.Frontiers in cell and developmental biology · 2020Review
- Clinical and translational pharmacology of the cathepsin K inhibitor odanacatib studied for osteoporosis.British journal of clinical pharmacology · 2019Review
- Advances in the discovery of cathepsin K inhibitors on bone resorption.Journal of enzyme inhibition and medicinal chemistry · 2018Review
- Bone-targeted agents in multiple myeloma.Hematology reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
backgroundONO-5334 is a cathepsin K inhibitor that induced bone mineral density (BMD) gain in a phase II study in postmenopausal osteoporosis patients. Even though the antiresorptive effect could only be monitored in the morning during the study, simulation can allow the antiresorptive effect to be assessed over 24 h, with assessment of the relationship to BMD gain.
methodsInhibition of the serum C-telopeptide of type I collagen (sCTX) level at doses of ONO-5334 of 100 mg once daily (QD), 300 mg QD, and 50 mg twice daily (BID) was simulated using plasma ONO-5334 pharmacokinetic (PK) data for repeated dose administration in a phase I study and corresponding sCTX inhibition from the PK-pharmacodynamic (PK/PD) relationship. sCTX was selected because it has a high signal-to-noise ratio compared to other telopeptides. A negative sigmoidal shape for the PK/PD relationship between plasma ONO-5334 and sCTX levels was obtained in our previous study.
resultsThe simulated sCTX inhibition reached >99% of the maximal inhibitory effect (Emax) at 0.5 h in all treatment groups, and decreased to <80% Emax at 8 and 12 h at 50 mg BID and 100 mg QD, respectively. However, sCTX inhibition at 300 mg QD was maintained at ≥82% Emax over 24 h. The mean sCTX inhibition rates for 24 h at 100 mg QD, 300 mg QD and 50 mg BID were 63, 95 and 80% Emax, respectively. There was a positive linear relationship by treatment group between mean sCTX inhibition over 24 h and observed BMD gain in the phase II study.
conclusionThe dose response for BMD with ONO-5334 at 100 and 300 mg QD and higher BMD gain at 50 mg BID vs. 100 mg QD can be explained by sCTX inhibition over 24 h. The simulation gave the antiresorptive effect of ONO-5334 over 24 h and allowed prediction of BMD gain due to ONO-5334.
trial registrationThe registration number in The European Union Clinical Trials Register is 2007-002417-39 . The date of registration was August 31, 2007.
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