Efficacy and safety of 40 mg or 60 mg duloxetine in Japanese adults with diabetic neuropathic pain: Results from a randomized, 52-week, open-label study

Hitoshi Yasuda, Nigishi Hotta, Masato Kasuga, Atsunori Kashiwagi, Ryuzo Kawamori, Tadaaki Yamada, Yuko Baba, Levent Alev, Ko Nakajo, Hitoshi Yasuda, Nigishi Hotta, Masato Kasuga, Atsunori Kashiwagi, Ryuzo Kawamori, Tadaaki Yamada, Yuko Baba, Levent Alev, Ko Nakajo

Abstract

Introduction: To examine the long-term efficacy and safety of duloxetine in the treatment of Japanese patients with diabetic neuropathic pain, we carried out a 52-week, randomized, open-label extension of a 12-week, double-blind, placebo-controlled study.

Materials and methods: Japanese adults with diabetic neuropathic pain who completed the double-blind study were eligible for this long-term study, carried out at 71 sites in Japan (March 2008 to March 2010). Participants (n = 258) were re-randomized (1:1) to 40 mg/day or 60 mg/day duloxetine. Pain (Brief Pain Inventory severity and interference), quality of life (Patient's Global Impression of Improvement), and safety (primary outcome; adverse events, vital signs, metabolic measures) were measured.

Results: Significant (P < 0.0001) and sustained improvements (change ± standard deviation; n = 257) were observed in Brief Pain Inventory severity (average pain score -2.1 ± 1.7). Improvements were also seen in Brief Pain Inventory interference (mean of subscores -0.96 ± 1.52) and Patient's Global Impression of Improvement (-0.9 ± 1.1) scores; these scores decreased significantly (P < 0.0001) during the long-term study. Frequently reported adverse events included somnolence (13.6%), constipation (13.2%) and nausea (10.5%). Increases were observed in plasma glucose, glycosylated hemoglobin and total cholesterol levels, and in bodyweight and heart rate; however, none of these were clinically meaningful. Overall, there were no clinically significant safety concerns.

Conclusions: This is the first publication of a long-term study carried out in Asia with an entirely Japanese patient population to suggest that long-term duloxetine therapy for diabetic neuropathic pain is effective and has an acceptable safety profile.

Trial registration: ClinicalTrials.gov NCT00641719.

Keywords: Diabetes‐related complications; Diabetic neuropathy (painful); Duloxetine.

Figures

Figure 1
Figure 1
Participant flow diagram for the double‐blind (DB) and open‐label extension (OLE) studies. †One participant did not receive any study drug and was not assessed at any study visits after the start of the double‐blind study; this participant was excluded from the analysis. ‡One participant discontinued during the taper phase, not the treatment phase. AE, adverse event.
Figure 2
Figure 2
Mean (±standard deviation) change from the start of the long‐term study in Brief Pain Inventory (BPI) severity – average pain score, Patient's Global Impression of Improvement (PGI‐I) score and BPI interference subscores at the end of the long‐term study. Results from the combined duloxetine group (40 mg/day and 60 mg/day, n = 257) are presented. All scores decreased significantly from the start of the long‐term study (P < 0.0001 for all scores; Wilcoxon's signed‐rank test).
Figure 3
Figure 3
Mean (±standard deviation) change in Brief Pain Inventory (BPI) severity – average pain scores during the long‐term study (50/51 weeks). Results from the combined duloxetine group (40 mg/day and 60 mg/day, n = 191–258) are presented.
Figure 4
Figure 4
Proportion of participants at each Patient's Global Impression of Improvement (PGI‐I) scale level at the start (n = 258) and at the end of the long‐term study (last observation carried forward; n = 257). Results from the combined duloxetine group (40 mg/day and 60 mg/day) are presented.

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