A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis

• Published in: Clinics in orthopedic surgery Vol. 9; no. 4; pp. 439 - 457
• Main Authors: Lee, Myungchul, Yoo, Juhyung, Kim, Jin Goo, Kyung, Hee-Soo, Bin, Seong-Il, Kang, Seung-Baik, Choi, Choong Hyeok, Moon, Young-Wan, Kim, Young-Mo, Han, Seong Beom, In, Yong, Choi, Chong Hyuk, Kim, Jongoh, Lee, Beom Koo, Cho, Sangsook
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Orthopaedic Association 01.12.2017; 대한정형외과학회
• Subjects: Adult; Aged; Aged, 80 and over; Celecoxib - adverse effects; Celecoxib - therapeutic use; Cyclooxygenase 2 Inhibitors - adverse effects; Cyclooxygenase 2 Inhibitors - therapeutic use; Double-Blind Method; Female; Furans - adverse effects; Furans - therapeutic use; Gastrointestinal Diseases - chemically induced; Humans; Male; Middle Aged; Musculoskeletal Pain - drug therapy; Musculoskeletal Pain - etiology; Original; Osteoarthritis, Hip - complications; Osteoarthritis, Hip - drug therapy; Osteoarthritis, Hip - physiopathology; Osteoarthritis, Knee - complications; Osteoarthritis, Knee - drug therapy; Osteoarthritis, Knee - physiopathology; Range of Motion, Articular; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; 정형외과학; Cyclooxygenase 2 inhibitor; Celecoxib; Osteoarthritis; Placebo; Polmacoxib
• ISSN: 2005-291X; 2005-4408; 2005-4408
• DOI: 10.4055/cios.2017.9.4.439

The aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA). This study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations. After 6 weeks, the polmacoxib-placebo treatment difference was -2.5 (95% confidence interval [CI], -4.4 to -0.6; = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, -0.9 to 2.2; = 0.425). According to Physician's Global Assessments, more subjects were "much improved" at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo. Polmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA.