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Safety and Pharmacokinetics of ReN1869: A First Human Dose Study in Healthy Subjects after Single-Dose Administration

From Clinical Pharmacology (B. K. Skrumsager) and Pharmacokinetics (S. H. Ingwersen), Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark, and Pharma Bio-Research International B.V., Zuidlaren, the Netherlands (M. Gerrits).

ReN1869 (NNC 05-1869) is a novel, selective H₁ receptor antagonist that has been developed for analgesic purposes. In a first human dose administration study, the safety and pharmacokinetics of seven single oral doses in the range of 3.5 to 95 mg ReN1869 were studied. The study was a randomized, double-blind, placebo-controlled, dose-escalating study in 56 healthy subjects. No serious or severe adverse events were reported. After active doses, an average of 0.6 adverse events (AEs) was reported per subject in comparison to 0.5 AEs per subject after placebo, and the frequency of subjects reporting AEs was not related to dose level. The most frequently reported adverse events were dizziness, fatigue, and somnolence, and their occurrence was not proportional to dose. Vital signs, ECG recordings, and clinical laboratory results showed no changes of clinical relevance. During telemetric monitoring at all dose levels until 4 hours after dosing, no clinically relevant abnormalities were observed. A maximally tolerated dose was not identified. ReN1869 was rapidly absorbed after dosing. The overall mean value of t_1/2 and oral clearance was 4.7 hours and 11.7 L/h, respectively. The parameters C_max and AUC increased proportionally with dose level, whereas all other pharmacokinetic parameters were independent of the dose. In conclusion, single-dose administration of ReN1869 in doses up to 95 mg exhibited very few adverse events and no clinically relevant effects on any of the observed safety parameters. The pharmacokinetics points to simple first-order pharmacokinetics for ReN1869. All together, it makes ReN1869 a potential new drug candidate for the treatment of chronic pain and inflammatory conditions of neurogenic origin.

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