| Summary: | Hiroyuki Enomoto,1 Hitoshi Yasuda,2 Atsushi Nishiyori,3 Shinji Fujikoshi,4 Masashi Furukawa,5 Mitsuhiro Ishida,6 Masashi Takahashi,1 Toshinaga Tsuji,7 Aki Yoshikawa,8 Levent Alev9 1Bio-Medicine, Medicines Development Unit, Eli Lilly Japan K.K, Tokyo, Japan; 2Foundation of Shiga Health Research Center, Shiga, Japan; 3Project Management, Global Development Division, Shionogi & Co. Ltd., Osaka, Japan; 4Statistical Science, Medicines Development Unit, Eli Lilly Japan K.K., Kobe, Japan; 5Biostatistics, Biostatistics Department, Shionogi & Co. Ltd., Osaka, Japan; 6Clinical Research Development, Shionogi & Co. Ltd., Osaka, Japan; 7Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Japan; 8Scientific Communications, Medicines Development Unit, Eli Lilly Japan K.K, Kobe, Japan; 9Eli Lilly, Medical Department, Lilly Turkey, Istanbul, Turkey Purpose: Duloxetine and pregabalin are recommended as first-line treatments for diabetic peripheral neuropathic pain (DPNP). However, studies have not reported a direct comparison between duloxetine and pregabalin. We conducted a postmarketing, randomized, double-blind study to assess the noninferiority of duloxetine compared with pregabalin after 12 weeks of treatment in adult patients with DPNP in Japan (NCT02417935). Patients and methods: Patients (N = 303) with distal symmetrical DPNP were randomized to and were administered duloxetine (40–60 mg/day) or pregabalin (300–600 mg/day). The primary endpoint was the change from baseline in weekly mean of the 24-hour average pain score (numeric rating scale [NRS]). Noninferiority of duloxetine compared with pregabalin was assessed with the primary endpoint at week 12. Secondary measures, including night pain and worst pain, Brief Pain Inventory-Severity and Interference rating short form (BPI-SF), Clinical Global Impression of Improvement (CGI-I), Patient Global Impression of Improvement (PGI-I), and Neuropathic Pain Symptom Inventory (NPSI), health outcome measures (EuroQol 5-Dimension index and VAS), and safety were also assessed. Results: For the 24-hour NRS average pain score, the difference between the duloxetine and pregabalin groups was 0.072 (95% CI: – 0.295, 0.439), and the upper bound of the 95% CI (0.439) did not exceed the predefined noninferiority margin (0.51), at the end of the study period. For secondary outcome measures (night pain, worst pain, BPI-SF, CGI-I, PGI-I, NPSI) and health outcome measures, both the duloxetine and pregabalin treatment groups showed an improvement from baseline with no significant between-group difference. Duloxetine and pregabalin were well tolerated and the safety profiles were consistent with previously reported results. Conclusion: This study demonstrated the noninferior efficacy of duloxetine compared with pregabalin in the treatment of adult patients with DPNP. The safety analyses showed an acceptable tolerability based on safety profiles of duloxetine and pregabalin. Keywords: serotonin and norepinephrine reuptake inhibitor, diabetic peripheral neuropathic pain, duloxetine, Japan, noninferiority, pregabalin
|
|---|
