Abstract

Purpose: In regard to the current scientific discussion, this analysis aims to broaden the database for a risk evaluation of First-in-Human (FiH) trials with healthy volunteers.
Materials and methods: Study documents of each FiH study conducted between 2006 and 2016 for Bayer Clinical Pharmacology Cardiovascular were reviewed for inclusion. Study types, treatments, dose steps, study population, number, incidence, and intensity of treatment-emergent adverse events (AEs) were cumulatively analyzed using descriptive statistics. A comparison to a previous similar analysis (period 2000 – 2005) was made.
Results: 22 out of 25 studies were included (20 small molecules, 2 biologics) investigating drugs for cardiovascular (9), hematological (7), pulmonary (3), kidney (2), and metabolic (1) diseases. The mean age of subjects was 34.2 years. 1,250 subjects received treatment (950 active, 300 placebo). 952 AEs occurred (0.76 AEs/treatment, 0.85 AEs/active treatment, 0.49 AEs/placebo treatment). 88.2% (840/952) of AEs were mild, 11.3% (108/952) moderate, and 0.4% (4/952) were severe. 0.4% (5/1250) of subjects had active drug- or procedure-related serious AEs. The most frequent AE was headache (12.9% (123/952)), the mostly affected system organ class was CNS (14.4% of all subjects). The relative risk for an AE was significantly higher under active drug compared to placebo (1.24, 95% LCL >1). The incidence of AEs increased with higher dose steps. A higher incidence of AEs (active and placebo) in recent compared to previous studies was observed.
Conclusion: The risk of severe harm for healthy participants was low. The risk to experience any AE was higher under active drug compared to placebo. A trend change towards more frequent reporting of AEs in the recent studies was observed.

Author Details

Authors

• David Jung
• Michael-Friedrich Boettcher
• Georg Wensing


Departments

• Clinical Pharmacology Cardiovascular, Bayer AG, Wuppertal, Germany

Address


Dr. med. David Jung

Clinical Pharmacology Cardiovascular, Bayer AG
Aprather Weg 18a, 42113 Wuppertal, Germany
Email: [email protected]

Citation