Corrections to: Once-daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study

This article refers to:

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study

Arnold LM, Arsenault P, Huffman C, Patrick JL, Messig M, Chew ML, Sanin L, Scavone JM, Pauer L, Clair AG. Once-daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study. Curr Med Res Opin. 2014;30(10):2069-83.

This article reported on the results of a phase III clinical study of a once-daily controlled-release (CR) formulation of pregabalin for the treatment of patients with fibromyalgia (ClinicalTrials.gov identifier: NCT01271933). Following publication, amendments were made to the clinical study report. This has necessitated revisions to the article but has not altered the overall interpretation of the study results.

Full details of the revisions are as follows:

1. A correction was made regarding how study centers were pooled in the secondary efficacy analyses reported in Table 3. Minor changes were made to Table 3 (not shown here); all p-values remained non-significant.

2. Previously, adverse events (AEs) occurring in the single-blind (SB) phase and continuing into the double-blind (DB) phase were represented in summary tables of treatment-emergent AEs for both phases. The programming algorithm for treatment-emergent AEs has been revised to correct the double-counting of AEs in the DB phase, i.e. to only count events in the DB phase if they were new or more severe than in the SB phase. The amended data are provided here (see revised Table 5). In addition, the number of patients who permanently discontinued owing to the AE of peripheral edema in the SB phase decreased from 7 to 6.

   Table 5. Summary of treatment-emergent AEs (single-blind analysis set and full analysis set – all causality).

   Summary of AEs	Single-blind analysis set	Double-blind full analysis set
   	Pregabalin CR (n = 441), n (%)	Pregabalin CR (n = 63), n (%)	Placebo^a (n = 58), n (%)
   All AEs	353 (80.0)	34 (54.0)	27 (46.6)
   Serious AE	5 (1.1)	2 (3.2)	0 (0.0)
   Severe AE	28 (6.3)	5 (7.9)	0 (0.0)
   Discontinuation owing to AE	54 (12.2)	3 (4.8)	0 (0.0)
   Dose reduced or temporary discontinuation owing to AE	45 (10.2)	1 (1.6)	0 (0.0)
   All AEs occurring in ≥5% of patients in any treatment group
   Preferred term^b
   Dizziness	161 (36.5)	2 (3.2)	2 (3.4)
   Somnolence	105 (23.8)	0 (0.0)	0 (0.0)
   Headache	43 (9.8)	1 (1.6)	2 (3.4)
   Fatigue	42 (9.5)	1 (1.6)	0 (0.0)
   Nausea	41 (9.3)	5 (7.9)	0 (0.0)
   Weight increase	30 (6.8)	2 (3.2)	1 (1.7)
   Vision blurred	29 (6.6)	1 (1.6)	0 (0.0)
   Peripheral edema	27 (6.1)	6 (9.5)	2 (3.4)
   Dry mouth	25 (5.7)	0 (0.0)	2 (3.4)
   Disturbance in attention	24 (5.4)	0 (0.0)	0 (0.0)
   Insomnia	24 (5.4)	3 (4.8)	1 (1.7)
   Nasopharyngitis	3 (0.7)	1 (1.6)	3 (5.2)

   ^a Includes AEs from 1-week pregabalin taper at beginning of double-blind phase.

   ^b Medical Dictionary for Regulatory Activities, version 18.0 (MedDRA [v18.0]) coding dictionary applied.

3. Mean pain score calculations were corrected to require 4 observations in a 7-day period as per the pre-specified statistical analysis plan. This resulted in changes to both subject numbers and mean pain scores (see revised Figure 4).

   Figure 4. Weekly mean pain scores taken form daily pain diaries (11-point numeric rating scale from 0 [no pain] to 10 [worst possible pain]) during the single-blind and double-blind treatment phases. Single-blind baseline (SBB; n = 441), double-blind baseline (placebo, n = 58; pregabalin controlled-release, n = 63), double-blind endpoint (DBE; placebo, n = 58; pregabalin controlled-release, n = 62). DBE represents the mean of the last 7 day diary scores during the double-blind phase, last observation carried forward. CR, controlled-release; PBO, placebo; PGB, pregabalin.

   

4. The following amendments were made after a quality control check of the clinical study report:

   1. For the primary endpoint, the p-value associated with the time to loss of therapeutic response (LTR) for patients treated with pregabalin CR versus placebo changed from 0.0214 to 0.0186, and the median time to LTR changed from 22 to 23 days for the placebo group (see revised Table 2). The hazard ratio changed from 0.590 to 0.582 and remained statistically significant. There were minor adjustments in 95% confidence intervals.

      Table 2. Summary of Kaplan-Meier estimates of time to LTR by treatment group.

      Treatment	N	Time to LTR (95% CI), days		p Value comparison with placebo^b	Patients with LTR by end of double-blind phase, n (%)
      		First quartile^a	Median
      Placebo	58	10 (9–13)	23 (14–41)		41 (70.7)
      Pregabalin CR (330–495 mg)	63	20 (11–44)	58 (45–NA)	0.0186	34 (54.0)

      ^a One-quarter of patients lost therapeutic response by the day listed.

      ^b Calculated using the log-rank test.

      CI, confidence interval; CR, controlled-release; LTR, loss of therapeutic response; NA, no upper limit available.

   2. The percentage of patients in the SB phase reporting benefit from treatment changed from 83.8% to 83.3%.

   3. The percentage of patients showing clinically significant abnormalities in laboratory tests changed from 19% to 20% in the SB phase; and in the DB phase, decreased from 24% to 23% for pregabalin CR-treated patients and from 21% to 16% for placebo-treated patients.

In summary, these corrections are considered minor and do not affect the overall interpretation of the study results.

Acknowledgments

This study was sponsored by Pfizer Inc. Medical writing support was provided by Diane Hoffman, PhD, of Engage Scientific Solutions and was funded by Pfizer Inc.