Efficacy and safety of nicoboxil/nonivamide ointment for the treatment of acute pain in the low back - A randomized, controlled trial

Abstract

Background: Until now, nonivamide/nicoboxil ointment has not been tested in a randomized trial for the treatment of acute non-specific low back pain.

Methods: This phase III randomized, double-blind, active- and placebo-controlled, multi-centre trial investigated efficacy, safety and tolerability of topical nicoboxil 2.5%/nonivamide 0.4% for treatment of acute non-specific low back pain [primary endpoint: pain intensity (PI) difference between pre-dose baseline and 8 h after the first application].

Results: Patients (n = 805), 18-74 years of age were treated for up to 4 days with nicoboxil 2.5%/nonivamide 0.4%, nicoboxil 2.5%, nonivamide 0.4% or placebo ointment. Pre-dose baseline pain intensity (6.6 on a 0- to 10-point numerical rating scale) was reduced by 1.049 points with placebo, by 1.428 points with nicoboxil, by 2.252 points with nonivamide and by 2.410 points with nicoboxil/nonivamide after 8 h (p < 0.0001 for nicoboxil/nonivamide vs. placebo, nicoboxil; p = 0.4171 for nicoboxil/nonivamide vs. nonivamide). At the end of treatment, the combination provided more pronounced PI reduction (3.540 points) compared with nicoboxil (2.371, p < 0.0001), nonivamide (3.074, p = 0.0259) and placebo (1.884, p < 0.0001). Low back mobility scores on Day 1 were better for the combination compared with all other treatments (p < 0.044); on Day 2-4, scores were better than for placebo and nicoboxil (p < 0.003). Patients assessed efficacy of the combination as greater than of the comparators (p ≤ 0.0129). All treatments were tolerated well. No treatment-related serious adverse events were reported.

Conclusion: Nicoboxil/nonivamide ointment is an effective, well-tolerated medication for the treatment of acute non-specific low back pain.

Trial registration: ClinicalTrials.gov NCT01708915.

Figure 1

Pain intensity differences (PIDs) up to 8 h after the first application of ointment containing placebo (PLA), nicoboxil, nonivamide or the combination of nicoboxil and nonivamide. Ointment was applied at 0 and 4 h. The combination reduced PID by more than 1 point compared with placebo, and by more than 2 points compared with baseline (BL). Data are shown as adjusted means with 95% confidence intervals (CI). The statistical model included baseline pain intensity, centre, time (0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h), treatment and treatment‐by‐time interaction.

Figure 2

Average pain intensity differences (APIDs) from Day 1 to Day 4. All treatments reduced APID over the treatment period, with the most pronounced effects for nicoboxil/nonivamide. The number of patients with available PI data for the treatment days shows that a relatively high number did not continue treatment over the entire (allowed) 4‐day period. Data are shown as adjusted means with 95% confidence intervals (CI). The statistical model included baseline pain intensity, centre, time (Day 1, Day 2, Day 3, Day 4), treatment and treatment‐by‐time interaction.