文献： Andrew S C R,et al.EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial.The Lancet, Early Online Publication, 5 February 2014.
帯状疱疹後神経痛患者183人を対象に、高度に選択的なアンジオテンシンIIタイプ１（AT2R）受容体拮抗薬EMA401の有効性を第2相無作為化プラセボ対照試験で検討。EMA401群はプラセボ群に比べ28日間の治療終了時の疼痛が有意に軽減した（疼痛スコアの平均減少−2.29対−1.60）。重篤な有害事象は見られなかった。
EMA401, an orally administered highly selective angiotensin II type 2 receptor antagonist, as a novel treatment for postherpetic neuralgia: a randomised, double-blind, placebo-controlled phase 2 clinical trial
Prof Andrew S C Rice MD a Corresponding AuthorEmail Address, Prof Robert H Dworkin PhD c, Tom D McCarthy PhD d, Prof Praveen Anand FRCP b, Prof Chas Bountra PhD e, Philip I McCloud PhD f, Julie Hill MSc f, Prof Gary Cutter PhD g h, Geoff Kitson BM BS d, Nuket Desem MBA d, Milton Raff FCA [SA] i j, for the EMA401-003 study group†
Summary
Background
Existing treatments for postherpetic neuralgia, and for neuropathic pain in general, are limited by modest efficacy and unfavourable side-effects. The angiotensin II type 2 receptor (AT2R) is a new target for neuropathic pain. EMA401, a highly selective AT2R antagonist, is under development as a novel neuropathic pain therapeutic agent. We assessed the therapeutic potential of EMA401 in patients with postherpetic neuralgia.
Methods
In this multicentre, placebo-controlled, double-blind, randomised, phase 2 clinical trial, we enrolled patients (aged 22—89 years) with postherpetic neuralgia of at least 6 months' duration from 29 centres across six countries. We randomly allocated 183 participants to receive either oral EMA401 (100 mg twice daily) or placebo for 28 days. Randomisation was done according to a centralised randomisation schedule, blocked by study site, which was generated by an independent, unmasked statistician. Patients and staff at each site were masked to treatment assignment. We assessed the efficacy, safety, and pharmacokinetics of EMA401. The primary efficacy endpoint was change in mean pain intensity between baseline and the last week of dosing (days 22—28), measured on an 11-point numerical rating scale. The primary efficacy analysis was intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000822987.
Findings
92 patients were assigned to EMA401 and 91 were assigned to placebo. The patients given EMA401 reported significantly less pain compared with baseline values in the final week of treatment than did those given placebo (mean reductions in pain scores −2·29 [SD 1·75] vs −1·60 [1·66]; difference of adjusted least square means −0·69 [SE 0·25]; 95% CI −1·19 to −0·20; p=0·0066). No serious adverse events related to EMA401 occurred. Overall, 32 patients reported 56 treatment-emergent adverse events in the EMA401 group compared with 45 such events reported by 29 patients given placebo.
Interpretation
EMA401 (100 mg twice daily) provides superior relief of postherpetic neuralgia compared with placebo at the end of 28 days of treatment. EMA401 was well tolerated by patients.
Funding
Spinifex Pharmaceuticals.
a Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
b Peripheral Neuropathy Unit, Division of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK
c School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA
d Spinifex Pharmaceuticals, Melbourne, VIC, Australia
e Structural Genomics Consortium and Department of Clinical Medicine, University of Oxford, Oxford, UK
f McCloud Consulting Group, Sydney, NSW, Australia
g University of Alabama at Birmingham, Birmingham, AL, USA
h Pythagoras, Birmingham, AL, USA
i Christiaan Barnard Memorial Hospital, Cape Town, South Africa
j Department of Anaesthesia, University of Cape Town, South Africa
Corresponding Author Information Correspondence to: Prof Andrew S C Rice, Pain Research, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital campus, London SW10 9NH, UK
† Members listed at end of paper
