PMID- 17697905 OWN - NLM STAT- MEDLINE DCOM- 20070905 LR - 20180312 IS - 0149-2918 (Print) IS - 0149-2918 (Linking) VI - 29 IP - 5 DP - 2007 May TI - Assessment of comparative pain relief and tolerability of SKI306X compared with celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, double-dummy, phase III, noninferiority clinical trial. PG - 862-873 LID - S0149-2918(07)00135-X [pii] LID - 10.1016/j.clinthera.2007.05.006 [doi] AB - BACKGROUND: SKI306X, which consists of biologically active ingredients from Clematis mandsburica, Tricbosantbes kirilowii, and Prunella vulgaris, was developed and tested in preclinical trials in Korea. Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect, and that it can delay the destruction of cartilage in rheumatoid arthritis (RA). OBJECTIVE: The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA. METHODS: This study was a 6-week, multicenter, randomized, double-blind, double-dummy, Phase III, noninferiority clinical trial. Eligible patients were aged 18 to 80 years, had a history of RA with a disease duration of > or =3 months, and were functional American College of Rheumatology (ACR) class I, II, or III before entry. After a washout period of 2 weeks, patients were randomized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks. The primary end point was a change in patient assessment of pain intensity using a visual analog scale (VAS). The secondary end points were a 20% improvement in response rate as defined by the ACR (ACR20) and the frequency of rescue medication use. Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator. RESULTS: Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and randomized to 1 of 2 treatment groups. Ninety-one patients (10 male, 81 female; mean [SD] age, 52.13 [12.64] years; mean [SD] duration of RA, 9.08 [10.23] years; no. [%] of ACR class I, II, and III, 13 [14.29], 44 [48.35] and 34 [37.36] patients, respectively) received SKI306X 200 mg TID and 92 patients (10 male, 82 female; mean [SD] age, 51.78 [10.94] years; mean [SD] duration of RA, 8.78 [7.78] years; no. [%] of ACR class I, II, and III, 14 [15.22], 44 [47.83], and 34 [36.96] patients, respectively) received celecoxib 200 mg BID. An analysis of the change in reported pain intensity as determined by VAS (mm) score between baseline and week 3 (mean [SD], 13.64 [16.62] vs 14.45 [15.89]), and between baseline and week 6 (18.4 [20.8] vs 17.9 [19.1], respectively) suggested that SKI306X was not inferior to celecoxib. The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 (16/87 [18.4%] vs 24/87 [27.6%], respectively) and at week 6 (29/87 [33.3%] vs 29/87 [33.3%]). The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 (54/87 [62.1%] vs 47/87 [54.0%], respectively) or week 6 (57/87 [65.5%] vs 49/87 [56.3%]). Drug-related AEs were reported by 27 (29.7%) patients in the SKI306X group and 22 (23.9%) patients in the celecoxib group. The most frequent drug-related AEs were epigastric pain (9/91 [9.9%]) in the SKI306X group and glutamyltranferase elevation (4/92 [4.3%]) in the celecoxib group. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs. CONCLUSION: The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA. FAU - Song, Yeong Wook AU - Song YW AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Electronic address: ysong@snu.ac.kr. FAU - Lee, Eun Young AU - Lee EY AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. FAU - Koh, Eun-Mi AU - Koh EM AD - Department of Internal Medicine, Samsung Medical Center, Seoul, Korea. FAU - Cha, Hoon-Suk AU - Cha HS AD - Department of Internal Medicine, Samsung Medical Center, Seoul, Korea. FAU - Yoo, Bin AU - Yoo B AD - Department of Internal Medicine, Asan Medical Center, Seoul, Korea. FAU - Lee, Chang-Keun AU - Lee CK AD - Department of Internal Medicine, Asan Medical Center, Seoul, Korea. FAU - Baek, Han Joo AU - Baek HJ AD - Department of Internal Medicine, Gachon Medical School, Gil Medical Center, Incheon, Korea. FAU - Kim, Hyun Ah AU - Kim HA AD - Department of Internal Medicine, Hallym University Sacred Heart Hospital, Pyengchon, Korea. FAU - Suh, Young 2nd AU - Suh Y 2nd AD - Department of Internal Medicine, Hallym University Sacred Heart Hospital, Pyengchon, Korea. FAU - Kang, Seong-Wook AU - Kang SW AD - Department of Internal Medicine, Chungnam National University Hospital, Daejoen, Korea. FAU - Lee, Yun Jong AU - Lee YJ AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. FAU - Jung, Hyung-Gi AU - Jung HG AD - Department of Biostatistics, Seo Kyeong University, Seoul, Korea. LA - eng PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antirheumatic Agents) RN - 0 (Cyclooxygenase 2 Inhibitors) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Pyrazoles) RN - 0 (SKI 306X) RN - 0 (Sulfonamides) RN - 9PHQ9Y1OLM (Prednisolone) RN - JCX84Q7J1L (Celecoxib) SB - IM MH - Anti-Inflammatory Agents MH - Antirheumatic Agents/*adverse effects/*therapeutic use MH - Arthritis, Rheumatoid/complications/*drug therapy MH - Celecoxib MH - Clematis MH - Cyclooxygenase 2 Inhibitors/*adverse effects/*therapeutic use MH - Double-Blind Method MH - Drugs, Chinese Herbal/*adverse effects/*therapeutic use MH - Female MH - Humans MH - Korea MH - Male MH - Middle Aged MH - Pain/*drug therapy/etiology MH - Pain Measurement MH - *Phytotherapy MH - Prednisolone/administration & dosage/therapeutic use MH - Prunella MH - Pyrazoles/*adverse effects/*therapeutic use MH - Sulfonamides/*adverse effects/*therapeutic use EDAT- 2007/08/19 09:00 MHDA- 2007/09/06 09:00 CRDT- 2007/08/19 09:00 PHST- 2007/02/23 00:00 [accepted] PHST- 2007/08/19 09:00 [pubmed] PHST- 2007/09/06 09:00 [medline] PHST- 2007/08/19 09:00 [entrez] AID - S0149-2918(07)00135-X [pii] AID - 10.1016/j.clinthera.2007.05.006 [doi] PST - ppublish SO - Clin Ther. 2007 May;29(5):862-873. doi: 10.1016/j.clinthera.2007.05.006.