Safety and Efficacy of the FLECTOR (Diclofenac Epolamine) Topical System in Children with Minor Soft Tissue Injuries: A Phase IV Non-randomized Clinical Trial

Abstract

Background and objective: A topical formulation of diclofenac (FLECTOR diclofenac epolamine topical system (FDETS)) is approved in adults for the treatment of acute pain due to minor strains, sprains, and contusions; however, its safety and efficacy have not been investigated in a pediatric population. This study assessed the safety and efficacy of the FLECTOR (diclofenac epolamine) topical system in children.

Methods: This was an open-label, single-arm, phase IV study at ten USA-based family medicine or pediatric practices in children aged 6-16 years with a clinically significant minor soft tissue injury sustained within the preceding 96 h and at least moderate spontaneous pain on the Wong-Baker FACES® Pain Rating Scale. The FLECTOR topical system was applied twice daily until pain resolution or Day 14. The primary endpoint was local tolerability and systemic safety. Key secondary endpoints were diclofenac plasma concentrations and analgesic efficacy.

Results: 104 patients were enrolled; 52 were 6-11 years old, and 52 were 12-16 years old (mean age 11.6 years). The maximum tolerability score experienced by any patient was 1 (faint redness). Fourteen adverse events (none serious) in nine patients (8.7%) were considered possibly treatment-related. Reduction in pain during the study was somewhat greater for patients aged 6-11 versus 12-16 years (p < 0.011). The diclofenac plasma concentration tended to be higher in the younger age group compared with older patients: 1.83 versus 1.46 ng/mL at the first assessment and 2.49 versus 1.11 ng/mL at the last assessment (p = 0.002).

Conclusion: The FLECTOR topical system safely and effectively provided pain relief for minor soft tissue injuries in the pediatric population, with minimal systemic nonsteroidal anti-inflammatory drug exposure and low potential risk of local or systemic adverse events.

Clinical trial registration: ClinicalTrials.gov identifier NCT02132247.

Conflict of interest statement

FH is an IBSA consultant. At the time of the study, CAJ and CJ were employees of IBSA Pharma Inc., a wholly-owned subsidiary of IBSA. VF is an employee of IBSA CH. GL and PPW have no financial interests in either FDETS or IBSA CH or its affiliate.

© 2021. The Author(s).

Figures

Fig. 1

Change from baseline in pain scores. Data from the two pediatric cohorts (6–11 years and 12–16 years) were compared with similar data from another study in adults (00GB/Fp05) included in the Flector New Drug Application submission to the US Food and Drug Administration. P values were derived from a generalized estimating equation (GEE) model with factors for treatment and day, and an independent correlation structure for repeated measures

Fig. 2

Plasma levels of diclofenac. Data from children aged 6–11 years and 12–16 years were compared to adults treated with either FDETS (two DETS/day for 4 days) or a single oral dose of 50 mg diclofenac sodium. Adult data were included in the Flector New Drug Application submission to the US Food and Drug Administration (Study CRO-PK-01-72). P values were derived from a generalized estimating equation (GEE) model with a factor for treatment, and an independent correlation structure for repeated measures. Cmax maximum plasma concentration