E-58425 / Purdue, Mundipharma, Esteve - LARVOL DELTA

Celecoxib-Tramadol Co-Crystal: a Randomized 4-Way Crossover Comparative Bioavailability Study. (PubMed, Clin Ther) - "The aim of this study was to compare the PK profile of the US-marketed tramadol and celecoxib products with CTC to determine their systemic exposure and to validate the dosing regimen for a subsequent pivotal factorial Phase 3study. PK parameters of each active component in CTC were favorably modified by co-crystallization and did not result in higher systemic exposure compared with US-marketed celecoxib, tramadol, and their concomitant administration. (Clin Ther. 2021;43:XXX-XXX)"

Clinical • Journal • Pain

"@ESTEVE_news y #KOWAPharmaceuticalsAmerica firman acuerdo exclusivo licencia y comercializar en #EEUU tratamiento potencial #doloragudo E-58425 nuevo co-cristal celecoxib y tramadol en investigación actualmente en revisión por @US_FDA #salud #PiscisComunicacion @alsoldelacosta" (@Acedotor)

Administration of a co-crystal of tramadol and celecoxib in a 1:1 molecular ratio produces synergistic antinociceptive effects in a postoperative pain model in rats. (PubMed, Eur J Pharmacol) - "Moreover, ctc showed similar efficacy but improved safety ratio (80, measured as gastrointestinal transit vs postoperative pain ED ratios) compared with the strong opioids morphine (2.5) and oxycodone (5.8). The overall in vivo profile of ctc supports the further investigation of CTC in the clinical management of moderate-to-severe acute pain as an alternative to strong opioids."

Journal • Preclinical • Biosimilar • CNS Disorders • Pain

Pharmaceutical and narcotic analgesics (Maekyung Media Group) - "...three pipelines of narcotic analgesics did not receive positive feedback at ADCOM, hosted by the Anesthetic and Analgesic Drug Products Advisory Committee...drug oxycodegol (NKTR-181) of Nektar herapeutics, a chronic low back pain treatment...No clinical trials were conducted, and all 27 consultants declined to approve because of concerns about drug abuse. Esteve pharmaceuticals 'tramadol and celecoxib combination drug E-58425 were found to be equal to 13:13..."

Non-US regulatory

Co-crystals as a new approach to multimodal analgesia and the treatment of pain. (PubMed, J Pain Res) - "In CTC neither of its three active components that have complementary mechanisms of action (ie, the two enantiomers of tramadol and celecoxib) show increased exposure levels versus commercially available single-entity reference products, but rather show a change in their PK profile with potential clinical advantages. CTC is in Phase III clinical development for the treatment of pain."

Journal

Co-crystal of tramadol-celecoxib: preclinical and clinical evaluation of a novel analgesic. (PubMed, Expert Opin Investig Drugs) - "Expert opinion: CTC may provide a relevant addition to pain therapy due to its: i) unique co-crystal structure conferring differentiated intrinsic dissolution profiles on constituent APIs, ii) modified clinical pharmacokinetics (slower absorption of tramadol and faster absorption of celecoxib) compared with commercially available single-entity reference products (in agreement with modified dissolution rates), iii) superior benefit-risk ratio compared with reference products (suggested by preclinical synergistic antinociceptive effects, without potentiation of adverse effects), and iv) efficacy in a phase 2 trial of moderate to severe pain following extraction of ≥2 impacted third molars requiring bone removal, where CTC doses containing low doses of APIs exerted a significant effect. Phase 3 studies are currently ongoing."

Journal • Review