Keynote Presentation: Discovery and Development of a Novel First-in-Class Resuscitative Agent

Centhaquine (previously used names, centhaquin and PMZ-2010; International Non-proprietary Name (INN) recently approved by WHO is centhaquine) is being developed by us as a first-in-class resuscitative agent for treating hypovolemic shock. It acts on the venous α2B-adrenergic receptors and enhances venous return to the heart, in addition, it produces arterial dilatation by acting on central α2A-adrenergic receptors to reduce sympathetic activity and systemic vascular resistance. Enhanced cardiac output and blood flow to the vital organs, prevents organ failure and improves survival and recovery of hypovolemic shock patients. Toxicological studies showed high safety margin in preclinical studies. Its safety and tolerability have been demonstrated in a human phase I study in 25 subjects (NCT02408731). Phase II human studies showed extraordinary efficacy in patients with hypovolemic shock. A prospective, multi-centric, randomized, double-blind, parallel, saline controlled phase II study was carried out with centhaquine as a resuscitative agent for hypovolemic shock (NCT04056065). A total of 50 subjects met inclusion and exclusion criteria and were included in the study. Systolic and diastolic blood pressure in control group improved but in centhaquine group a much more significant increase in systolic and diastolic blood pressure was observed 48 hours after resuscitation. Blood lactate levels decreased from 4.30 ± 0.96 at baseline to 3.19 ± 1.07 (p=0.7729) at day 3 in control and from 4.34 ± 0.78 at baseline to 1.44 ± 0.13 (p=0.0012) at day 3 in centhaquine cohort. Two patients died in control and none in centhaquine cohort. No incidence of drug related adverse event occurred. A phase III multi-centric, randomized, double-blind, parallel, controlled phase-III efficacy clinical study of centhaquine therapy in patients with hypovolemic shock (NCT04045327) has been completed in 105 patients with positive results. Centhaquine is an innovative drug product that is likely to provide significant benefit to an unmet life-threatening medical condition of hypovolemic shock.