Treatment of patients with diabetic peripheral neuropathic pain in China: a double-blind randomised trial of duloxetine vs. placebo

Abstract

Background: Duloxetine has been approved in the United States, European Union and some Asian countries for the treatment of diabetic peripheral neuropathic pain (DPNP). We assessed the efficacy and safety of duloxetine (60 mg once daily) compared with placebo in Chinese patients suffering from DPNP.

Methods: This was a phase 3, multicenter, randomised, double-blind, parallel, placebo-controlled, 12-week trial of the treatment of DPNP with duloxetine. Subjects were male and female outpatients ≥ 18 years of age with DPNP, as assessed by the Michigan Neuropathy Screening Instrument, and had a rating of ≥ 4 on the Brief Pain Inventory-Modified Short Form-Severity weekly average pain item. The primary efficacy measure was the reduction in pain severity from baseline to 12 weeks, as measured by the weekly mean of 24-h average pain ratings recorded in the patient's diary. Mean changes from baseline in efficacy measures were analysed by a restricted maximum likelihood-based, mixed-effects model repeated measures approach and by analysis of covariance.

Results: Of the 405 patients randomised, 203 patients were assigned to duloxetine 60 mg once daily and 202 patients were assigned to placebo. Duloxetine-treated patients showed significantly greater pain relief on 24-h average pain ratings compared with placebo-treated patients each week of the 12-week study period [week 12: least squares (LS) mean change duloxetine: -2.40, placebo: -1.97; LS mean change difference (95% confidence interval) = -0.43 (-0.82, -0.04), p = 0.030]. Compared with placebo, patients treated with duloxetine experienced higher rates of nausea (p = 0.010), somnolence (p < 0.001) and asthenia (p = 0.002).

Conclusions: Duloxetine-treated patients showed significantly greater pain relief compared with placebo-treated patients over the 12-week study period. Duloxetine was shown in Chinese patients to have a safety profile similar to that found in previous duloxetine trials.

Trial registration: ClinicalTrials.gov NCT01179672.

Figure 1

Study design. QD, once daily. ^aPatients randomised to duloxetine started treatment at 30 mg QD for the first week. ^bStudy Period III was a required taper and began either at the patient’s final visit for Study Period II (visit 8), or if a patient discontinued early after visit 4 (provided the patient was not discontinued due to suicide risk).

Figure 2

Subject disposition

Figure 3

Change from baseline in weekly mean of 24-h average pain severity for all randomised patients over 12 weeks of double-blind therapy. LS, least squares; N, number of patients in group. Repeated measures analysis model: Variable = Treatment + Investigator + Week + Baseline + Treatment × Week + Baseline × Week

Figure 4

Categorical analysis of patient responses on the Patient Global Impression of Improvement scale (duloxetine vs. placebo). N, number of patients in group. Frequencies were analysed using Fisher’s exact test