Journal of Clinical Trials
Open Access

Abstract

Design of a Multicenter, Randomized, Open Label, Parallel Group Study to Evaluate the Efficacy of Loxoprofen on Acute-Phase Reactions in Japanese Primary Osteoporosis Patients Treated with Zoledronic Acid

Nobukazu Okimoto, Akinori Sakai, Hidehiro Matsumoto, Satoshi Ikeda, Kunitaka Menuki, Toru Yoshioka, Tomohiro Kobayashi, Toru Ishikura and Saeko Fujiwara

Treatment of osteoporosis with once-yearly zoledronic acid was approved in September 2016 in Japan. Like other bisphosphonates, zoledronic acid causes acute-phase responses (APRs), which are more severe in Asian populations than in multinational populations. The aim of this multicenter, randomized, open label, parallel group study is to investigate the incidence of APRs in Japanese patients with primary osteoporosis in real clinical settings, and to test the hypotheses that APRs are suppressed by administering one of the most commonly used nonsteroidal anti-inflammatory drugs in Japan, loxoprofen, immediately after the treatment with zoledronic acid, and the incidence of APRs in patients with prior history of treatment with bisphosphonate is lower than that in naïve patients. A total of 400 patients aged 60 or older were randomly allocated to a zoledronic acid plus loxoprofen group or zoledronic acid group on a 1:1 basis. After the treatment, patients were observed for 7 days, during which patients will record APRs for the first 3 days, and body temperature and drugs taken for 7 days. Primary endpoints are incidence of APRs and increase in body temperature, and secondary endpoints are relationship between prior treatment for osteoporosis in the past 3 years versus incidence of APRs, and that versus a change in body temperature. Results supporting the hypotheses will indicate that APRs are manageable with loxoprofen, which patients likely already have, and the APRs will develop less frequently and be less severe in the following years, despite the high risk of APRs in Japanese patients.