The bradykinin-1 receptor antagonist fulmetibant in patients with diabetic neuropathic pain: the randomized, crossover, placebo-controlled, double-blind, phase 2a BRADiNP study

Abstract The BRADiNP study was a multicenter, randomized, double-blind, placebo-controlled, 2-treatment complete crossover study evaluating the efficacy and safety of the bradykinin 1 receptor antagonist fulmetibant in patients with diabetic neuropathic pain (DNP) (ClinicalTrials.gov NCT05219812). To be eligible for enrollment, patients had to be adults with type 1 or type 2 diabetes mellitus with painful distal symmetric sensorimotor neuropathy of >6 months' duration and neuropathic pain. After blinded washout of prior DNP treatment, patients were randomized 1:1 to start with either fulmetibant once daily or placebo in the first 4 weeks' treatment period and vice versa in the second period. The primary endpoint was the change from baseline in weekly mean 24-hour average pain intensity score at week 4. Seventy-nine participants were treated with fulmetibant (450 mg once daily), and 79 participants were treated with placebo; 75 participants completed treatment in both treatment periods. At week 4, the mean treatment difference was 0.07 (−0.170 to 0.314). Adverse events were mostly mild or moderate in severity and occurred in 51.3% of the treated participants (41.8% after treatment with fulmetibant and 32.9% after treatment with placebo). The results of this study show that preclinical efficacy seen with this bradykinin 1 receptor antagonist did not translate into a meaningful therapeutic approach for pain management in patients with DNP.