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High NSP levels can be detrimental, particularly in lung tissue, and inhibition of NSPs is therefore an interesting therapeutic opportunity in multiple lung diseases, including chronic obstructive pulmonary disease (COPD) and bronchiectasis. We conducted a randomized, placebo\u2010controlled, first\u2010in\u2010human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of the DPP1 inhibitor AZD7986 in healthy subjects. Pharmacokinetic and pharmacodynamic data were analyzed using nonlinear mixed effects modeling and showed that AZD7986 inhibits whole blood NE activity in an exposure\u2010dependent, indirect manner\u2014consistent with <jats:italic>in vitro<\/jats:italic> and preclinical predictions. Several dose\u2010dependent, possibly DPP1\u2010related, nonserious skin findings were observed, but these were not considered to prevent further clinical development. 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