SAN DIEGO, CA—Once daily controlled-release (CR) pregabalin significantly improved time to loss of therapeutic response vs. placebo in patients with fibromyalgia, a study presented at the 2013 ACR/ARHP Annual Meeting concluded.
Pregabalin, an alpha2-delta ligand, is currently indicated for the treatment of fibromyalgia as a twice-daily dose over a range of 300mg–450mg/day. A pregabalin CR formulation was developed to enable once-daily dosing.
Lesley M. Arnold, MD, of the University of Cincinnati College of Medicine, Cincinnati, OH, and colleagues conducted a 4-phase study that involved a 1-week baseline, 6-week single-blind, 13-week double-blind treatment, and a 1-week double-blind taper. The single-blind phase starting dose was 165mg/day and was titrated up to 495mg/day over the first 3 weeks based on efficacy and tolerability.
Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase compared to baseline were randomized 1:1 in the double-blind phase to continue pregabalin CR at the optimized dose (330mg–495mg/day) or matching placebo.
The primary end point, time to loss of therapeutic response during the double-blind phase, was defined as <30% pain response relative to baseline or discontinuation due to lack of efficacy or an adverse event (AE).
Patients were primarily white (81%) and female (89%); average age was 48 years and mean duration of fibromyalgia diagnosis was 5–6 years.
A total of 441 patients from the United States, Canada, India, and Taiwan who met ACR 1990 criteria for fibromyalgia were included in the single-blind phase of the study and were treated with pregabalin CR 165–495mg/day for 6 weeks. Compliance rate was 91% (defined as taking the dose within 1 hour of a meal).
Of the 441 patients, 121 (27%) completed the single-blind phase, had a ≥50% pain response, and were treated in the double-blind phase. The pregabalin CR 330–495mg/day arm included 63 patients with a 99% compliance rate and the placebo arm, 58 patients with a 100% compliance rate.
Median time from randomization to loss of therapeutic response was 58 days in the pregabalin CR group and 22 days in the placebo group (P=0.021). During the double-blind phase, 34 of 63 patients (54.0%) in the pregabalin CR group and 41 of 58 (70.7%) in the placebo group met the loss of therapeutic response criteria. Sensitivity analyses confirmed the robustness of the Kaplan-Meier estimates.
“In the single-blind phase, patients treated with pregabalin CR showed improvement on secondary end points related to pain, sleep, tiredness, and functional status,” she noted. “Trends continued in the double-blind phase, generally favoring pregabalin CR, but differences vs. placebo were not statistically significant.”
For example, in the single-blind phase, mean daily pain score decreased from 6.8 at baseline to 4.3 at Week 6. In the double-blind phase, the pregabalin CR group “tended to show better daily pain scores over the course of treatment vs placebo,” she said. However, the treatment groups were not significantly different at study end: pregabalin -3.1 and placebo, -2.5.
Patients treated with pregabalin CR were more likely to report a benefit from treatment during the double-blind phase vs. placebo (OR 2.29; P=0.0296).
In the single-blind phase, 54 (12.2%) discontinued due to an adverse event, as did 3 (4.8%) in the double-blind pregabalin group, 2 of whom had AEs considered related to pregabalin CR, confusional state and feeling abnormal. None of the patients in the placebo group discontinued treatment.
The most commonly reported treatment-emergent AEs were dizziness, somnolence, and peripheral edema.