Efficacy and safety of EMA401 in peripheral neuropathic pain: results of 2 randomised, double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy.

Abstract

ABSTRACT:

The analgesic efficacy and safety of 2 phase 2b studies of EMA401 (a highly selective angiotensin II type 2 receptor antagonist) in patients with postherpetic neuralgia (EMPHENE) and painful diabetic neuropathy (EMPADINE) were reported. These were multicentre, randomised, double-blind treatment studies conducted in participants with postherpetic neuralgia or type I/II diabetes mellitus with painful distal symmetrical sensorimotor neuropathy. Participants were randomised 1:1:1 to either placebo, EMA401 25 mg, or 100 mg twice daily (b.i.d) in the EMPHENE and 1:1 to placebo or EMA401 100 mg b.i.d. in the EMPADINE. The primary outcome for both the studies was change in weekly mean of the 24-hour average pain score, using a numeric rating scale from baseline to week 12. Both the studies were prematurely terminated due to preclinical hepatotoxicity on long-term dosing, although not observed in these studies. Out of the planned participants, a total of 129/360 (EMPHENE) and 137/400 (EMPADINE) participants were enrolled. The least square mean reduction in numeric rating scale pain score was numerically in favour of EMA401 100 mg arm in both EMPHENE (treatment difference: -0.5 [95% confidence interval: -1.6 to 0.6; P value: 0.35]) and EMPADINE (treatment difference: -0.6 [95% confidence interval: -1.4 to 0.1; P value: 0.10]) at the end of week 12. However, as the studies were terminated prematurely, no firm conclusion could be drawn but the consistent clinical improvement in pain intensity reduction across these 2 studies in 2 different populations is worth noting.

• Authors: Andrew S C Rice, Robert H Dworkin, Nanna B Finnerup, Nadine Attal, Praveen Anand, Roy Freeman, Alessandro Piaia, Francesca Callegari, Christie Doerr, Subhayan Mondal, Nisha Narayanan, Laurent Ecochard, Yanina Flossbach, Shaloo Pandhi
• Journal: Pain (Pain) Vol. 162 Issue 10 Pg. 2578-2589 (10 01 2021) ISSN: 1872-6623 [Electronic] United States
• PMID: 33675631 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 International Association for the Study of Pain.

Chemical References

• Benzhydryl Compounds
• EMA400
• Isoquinolines

Topics

• Benzhydryl Compounds
• Diabetes Mellitus
• Diabetic Neuropathies (drug therapy)
• Double-Blind Method
• Humans
• Isoquinolines
• Neuralgia (drug therapy)
• Neuralgia, Postherpetic (drug therapy)
• Treatment Outcome