PAIN+ CPN

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.

Physician rater

Painful diabetic peripheral neuropathy (PDN) is a crippling complication of all forms of diabetes mellitus (except probably gestational diabetes). Although many aspects of the pathobiology of PDN are currently known, highly effective pharmacotherapeutic options are rare. Gabapentanoids and anti-depressants are of some benefit in PDN, but the side effects related to these drugs are often undesirable. Therefore, new drug therapies have been trialled over the past few decades without a great breakthrough in a positive outcome. This BRADiNP Study shows negative results for the inadequate benefit of fulmetibant. As in the case of other drugs for PDN, this agent also showed bad side effects with only marginal improvement of pain. These negative results demand more proactive treatment options for this enigmatic disease.

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