An adaptive‐design dose‐ranging study of PD 0348292, an oral factor Xa inhibitor, for thromboprophylaxis after total knee replacement surgery

Summary Background PD 0348292 is an oral, selective, direct and reversible factor Xa inhibitor. This was an adaptive dose‐ranging study evaluating a 100‐fold PD 0348292 dose range in subjects undergoing total knee replacement (TKR). Objective To assess the efficacy and safety of a dose range of PD 0...

Full description

Saved in:
Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2013-08, Vol.11 (8), p.1503-1510
Main Authors: Cohen, A. T., Boyd, R. A., Mandema, J. W., DiCarlo, L., Pak, R.
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Aged
Aged, 80 and over
anticoagulants
Arthroplasty, Replacement, Knee - methods
Computer Simulation
Dose Response Relationship
Dose-Response Relationship, Drug
Drug
Enoxaparin - pharmacology
Factor Xa Inhibitors
Female
Humans
Male
Middle Aged
Probability
Pyridones - pharmacology
Pyrrolidines - pharmacology
research design
Thromboembolism - drug therapy
Thromboembolism - prevention & control
total knee replacement
Treatment Outcome
venous thromboembolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Background PD 0348292 is an oral, selective, direct and reversible factor Xa inhibitor. This was an adaptive dose‐ranging study evaluating a 100‐fold PD 0348292 dose range in subjects undergoing total knee replacement (TKR). Objective To assess the efficacy and safety of a dose range of PD 0348292 relative to enoxaparin for the prevention of venous thromboembolism (VTE). Methods Extensive dose‐response modeling and trial simulations were used to select the PD 0348292 dose range for the Phase 2 study. Subjects were randomized to a blinded PD 0348292 dose (0.1 mg qd to 10 mg qd) or open‐label enoxaparin (30 mg bid) for 6–14 days after TKR surgery. Efficacy was assessed by mandatory bilateral venography. Results were analyzed using a dose‐response modeling approach. Results Observed VTE frequency ranged from 1.4–37.1% across PD 0348292 doses and was 18.1% for enoxaparin. The PD 0348292 dose‐response relationship for VTE was statistically significant (P 
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.12328