M. van den Boer,1 A. Van Peer,2 J. Vandenbossche,2 J. Biewenga,2 J. Bevernage,3 J. Lenz,4 S. Mesens,1 J. Van hove,1 M. Raghoebar1; 1Clinical Pharmacology Unit Janssen R&D, Merksem, Belgium, 2Clinical Pharmacology, Janssen R&D, Beerse, Belgium, 3Pharmaceutical and Material Sciences, Janssen R&D, Beerse, Belgium, 4Department Gastro-enterology, ZNA Hospital Jan Palfijn, Merksem, Belgium
BACKGROUND: The primary objective of this study was to collect duodenal samples in fasted and fed state. Samples will be used as pools for solubility testing and dissolution assessments. Secondary objectives were investigation of the safety, tolerability and evaluation of composition of the fluids.
METHODS: An open-label, methodological study without investigational product. After the placement of a catheter, sampling was performed in fasted and fed state. Subjects were healthy volunteers (16) (men and women, 18 to 45 years of age, BMI between 18 and 30 kg/m², and body weight >50 kg). pH and volume of the samples safety and tolerability were monitored continuously. Further analysis of fluid composition included pH and bile salt concentration. No statistical evaluation was performed.
RESULTS: The median volume collected per 10-minute sampling interval in fasted state was 1.95 mL (0-46.6mL) and in fed state 5.70 mL (0-138mL). Two catheters were located in the stomach. A total amount of 691 mL was collected in the fasted and 1381 ml in the fed state. Median baseline concentrations of total bile acids were approximately 1.6 mg/mL. Between subjects, a large variation was observed in the composition and amount of bile salts present in the duodenal aspirates. Within subjects, however, the relative contribution of each bile salt to the total bile salt content remained fairly constant regardless the nutritional state. The median sample pH in the fasted state was 6.1 (2.2-8.2) and in the fed state 6.0 (1.9-7.7). Only mild AEs were observed (sore throat (3) and headache (2)).
CONCLUSION: The procedure was well-tolerated. 691 mL fluid was collected in fasted and 1381 mL in fed state. Samples will be pooled based on sample characteristics and used for future investigation of solubility and dissolution of drug products.