A randomized, double-blind, placebo-controlled Phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis

Abstract

Purpose: To examine the efficacy and safety of duloxetine in Japanese patients with knee pain due to osteoarthritis.

Patients and methods: Patients were randomized to receive duloxetine 60 mg/day or placebo for 14 weeks in a double-blind manner (ClinicalTrials.gov Identifier: NCT02248480). The primary efficacy endpoint was mean change in Brief Pain Inventory pain severity (BPI-Severity) average pain. Secondary endpoints included improvement in other BPI-Severity scales, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, health-related quality of life (HRQoL) scales, range of motion of the knee joint, safety and tolerability, and structural changes on X-ray images.

Results: Of the 354 randomized patients, 161 in the duloxetine group and 162 in the placebo group completed the study. BPI-Severity average pain improved significantly with duloxetine vs. placebo (-2.57 vs. -1.80; adjusted mean difference: -0.77; 95% CI: -1.11 to -0.43; P<0.0001). Secondary efficacy endpoints and most HRQoL scales showed greater improvements in the duloxetine group than the placebo group. Adverse events observed in ≥5% of patients that were more frequent in the duloxetine than placebo group were somnolence, constipation, dry mouth, nausea, malaise, and decreased appetite. There were no marked changes in range of motion of the knee joint (efficacy), X-ray images, or Kellgren-Lawrence grade (safety) in either group.

Conclusion: Duloxetine reduced pain and improved function in patients with knee osteoarthritis, without causing X-ray abnormalities or altered knee joint mobility. Reduced pain was associated with improved HRQoL. Adverse events were consistent with duloxetine's known safety profile.

Keywords: double-blind; duloxetine; osteoarthritis; placebo-controlled trial; randomized.

Figure 1

Study design.

Figure 2

Patient disposition.

Figure 3

Primary endpoint: change in BPI-Severity average pain. Notes: Values are shown as the adjusted mean changes from baseline for duloxetine and placebo. Error bars indicate 95% CI and values in brackets indicate standard error. Abbreviation: BPI, Brief Pain Inventory.

Figure 4

Changes in WOMAC total (A), pain (B), stiffness (C), and physical function (D) scores. Notes: Values are shown as the adjusted mean changes from baseline for duloxetine and placebo. Error bars indicate 95% CI and values in brackets indicate standard error. Abbreviation: WOMAC, Western Ontario and McMaster Universities osteoarthritis index.