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Concerns about drug\u2013drug interactions (DDIs) have meant patients receiving drugs that inhibit CYP3A4 were ineligible for acumapimod trials. We report on how 2 acumapimod clinical DDI studies and a physiologically\u2010based pharmacokinetic (PBPK) model assessing how co\u2010administration of a weak (azithromycin) and strong (itraconazole) CYP3A4 inhibitor affected acumapimod systemic exposure, informed decision making and supported concomitant use of CYP3A4 and P\u2010gp inhibitors. Studies MBCT102 and MBCT103, respectively, demonstrated that co\u2010administration of azithromycin or itraconazole had no clinically meaningful impact on acumapimod pharmacokinetics. Findings were consistent with PBPK model results. Safety profiles were similar when acumapimod was co\u2010administered with azithromycin or itraconazole. 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