5% lidocaine medicated plaster versus pregabalin in post-herpetic neuralgia and diabetic polyneuropathy: an open-label, non-inferiority two-stage RCT study

ABSTRACT

Objective: To compare efficacy and safety of 5% lidocaine medicated plaster with pregabalin in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN).

Study design and methods: This was a two-stage adaptive, randomized, open-label, multicentre, non-inferiority study. Data are reported from the initial 4-week comparative phase, in which adults with PHN or painful DPN received either topical 5% lidocaine medicated plaster applied to the most painful skin area or twice-daily pregabalin capsules titrated to effect according to the Summary of Product Characteristics. The primary endpoint was response rate at 4 weeks, defined as reduction averaged over the last three days from baseline of ≥2 points or an absolute value of ≤4 points on the 11-point Numerical Rating Scale (NRS-3). Secondary endpoints included 30% and 50% reductions in NRS-3 scores; change in allodynia severity rating; quality of life (QoL) parameters EQ-5D, CGIC, and PGIC; patient satisfaction with treatment; and evaluation of safety (laboratory parameters, vital signs, physical examinations, adverse events [AEs], drug-related AEs [DRAEs], and withdrawal due to AEs).

Results: Ninety-six patients with PHN and 204 with painful DPN were analysed (full analysis set, FAS). Overall, 66.4% of patients treated with the 5% lidocaine medicated plaster and 61.5% receiving pregabalin were considered responders (corresponding numbers for the per protocol set, PPS: 65.3% vs. 62.0%). In PHN more patients responded to 5% lidocaine medicated plaster treatment than to pregabalin (PPS: 62.2% vs. 46.5%), while response was comparable for patients with painful DPN (PPS: 66.7% vs 69.1%). 30% and 50% reductions in NRS-3 scores were greater with 5% lidocaine medicated plaster than with pregabalin. Both treatments reduced allodynia severity. 5% lidocaine medicated plaster showed greater improvements in QoL based on EQ-5D in both PHN and DPN. PGIC and CGIC scores indicated greater improvement for 5% lidocaine medicated plaster treated patients with PHN. Improvements were comparable between treatments in painful DPN. Fewer patients administering 5% lidocaine medicated plaster experienced AEs (safety set, SAF: 18.7% vs. 46.4%), DRAEs (5.8% vs. 41.2%) and related discontinuations compared to patients taking pregabalin.

Conclusion: 5% lidocaine medicated plaster showed better efficacy compared with pregabalin in patients with PHN. Within DPN, efficacy was comparable for both treatments. 5% lidocaine medicated plaster showed a favourable efficacy/safety profile with greater improvements in patient satisfaction and QoL compared with pregabalin for both indications, supporting its first line position in the treatment of localized neuropathic pain.

Key words: :

• Diabetic neuropathies
• Lidocaine plaster
• Neuralgia
• postherpetic
• Neuropathic pain
• Polyneuropathy
• Pregabalin

Transparency

Declaration of funding

Grünenthal GmbH sponsored this study and provided funding for editorial assistance in the preparation of this manuscript. No honorarium was paid to the authors for the preparation of this article. The authors retain sole responsibility for the views expressed in this article, which may or may not be shared by the sponsors.

Declaration of financial/other relationships

R.B. has disclosed that he has received honoraria from Allergan, Schwarz, Pfizer, Grünenthal, Medtronic, Mundipharma, Eisai, Sanofi-Pasteur and Genzyme and received research funding from Pfizer, Grünenthal and Genzyme. A.B. has disclosed he has received honoraria from Allergan, Schwarz, Pfizer and Grünenthal. V.M. has disclosed that he has received honoraria from Grünenthal. G.L. has disclosed no relevant financial relationships. I.S. has disclosed she is an employee of Grünenthal. M.G.S. has disclosed he has received honoraria from Grünenthal and that his institution received remuneration to cover costs of patient visits and recruitment during the study.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 and Peer Reviewer 2 have disclosed they have no relevant financial relationships.

Acknowledgements

Medical writing assistance was provided by Julian Martins of Wolters Kluwer Health and was funded by Grünenthal GmbH.

The authors would like to thank the following study investigators: Prof. Dr G. Nell, Dr M. De Meulemeester, Dr H. Radovan, Dr M. Petr, Dr V. Stanislav, Dr V. Dana, Dr Z. Šolle, O. Vyšata, Dr B. Steinberg, Minnich J., Dr M. Sanuri, Prof. Dr D. Ziegler, Dr B. Bergtholdt, Laus S., Lehmann R., Dr H.-D. Stahl, Dr S. Mindt-Prüfert, Dr T. Meier, Dr J. Ignacio Calvo, Dr R. Gálvez, Dr L. Miguel Torres, Dr E. Catalá, Dr J. Guitart, Dr M. Blagden, Dr B. Silvert, Dr D. Haworth, Dr S. Ratcliffe, Dr P. D. Rogers, Dr M. Fingler, Dr I. Adanic-Mikloska, Dr A. Barada, Dr M. Persoli, Dr D. Spisic, Dr C. Power, Dr G. Lauria, Dr R. Casale, E. Motta, K. Boczar, M. Koziol, A. Szczepańska-Szerej, J. Pyszkowska, D. Szewczyk-Urgacz, Dr M. Miguel Rosa, Dr R. Duarte, Prof. I. Demidova, Prof. I. Gurieva, G. Požlep, A. Pražnikar, N. Krčevski-Škvarč.