Clin Orthop Surg.  2017 Dec;9(4):439-457. 10.4055/cios.2017.9.4.439.

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

• Lee M
• Yoo J
• Kim JG
• Kyung HS
• Bin SI
• Kang SB
• Choi CH
• Moon YW
• Kim YM
• Han SB
• In Y
• Choi CH
• Kim J
• Lee BK
• Cho S

• KMID: 2412245
• DOI: http://doi.org/10.4055/cios.2017.9.4.439

Abstract

BACKGROUND
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).
METHODS
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.
RESULTS
After 6 weeks, the polmacoxib-placebo treatment difference was −2.5 (95% confidence interval [CI], −4.4 to −0.6; p = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, −0.9 to 2.2; p = 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.
CONCLUSIONS
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.

Keyword

Osteoarthritis; Polmacoxib; Placebo; Celecoxib; Cyclooxygenase 2 inhibitor

MeSH Terms

Adult
Aged
Aged, 80 and over
Celecoxib/adverse effects/*therapeutic use
Cyclooxygenase 2 Inhibitors/adverse effects/*therapeutic use
Double-Blind Method
Female
Furans/adverse effects/*therapeutic use
Gastrointestinal Diseases/chemically induced
Humans
Male
Middle Aged
Musculoskeletal Pain/*drug therapy/etiology
Osteoarthritis, Hip/complications/*drug therapy/physiopathology
Osteoarthritis, Knee/complications/*drug therapy/physiopathology
Range of Motion, Articular
Sulfonamides/adverse effects/*therapeutic use
Cyclooxygenase 2 Inhibitors
Furans
Sulfonamides
Celecoxib

Figure

• 

  Fig. 1 Subject disposition throughout the 6-week period.

• 

  Fig. 2 Efficacy endpoints among treatment groups: least square (LS) mean changes from baseline in the WOMAC-pain subscale (A), total WOMACOA index score (B), WOMAC-stiffness subscale (C), and WOMAC-physical function subscale (D) at weeks 3 and 6 (intent-to-treat population, baseline observation carried forward). Data shown below the brackets are estimated treatment differences with 95% confidence intervals and p-values. The text in red indicates the upper confidence interval. Noninferiority can be inferred, as the predefined noninferiority margin for the WOMAC-pain subscale (A) was a score of 5 (10% of the total score), total WOMAC-OA index (B) was a score of 24 (10% of the total score), WOMAC-stiffness subscale (C) was a score of 2 (10% of the total score), and WOMAC-physical function subscale (D) was a score of 17 (10% of the total score). WOMAC: Western Ontario and McMaster Universities, OA: osteoarthritis.

• 

  Fig. 3 Efficacy endpoints among treatment groups: mean WOMAC questionnaire scores by time point and treatment group (intent-to-treat population). (A) WOMAC-pain subscale. (B) Total WOMAC-OA index score. (C) WOMAC-stiffness subscale. (D) WOMAC-physical function subscale. WOMAC: Western Ontario and McMaster Universities, OA: osteoarthritis.

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