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Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of a BI 653048 BS H3PO4 Capsule Formulation Administered as Multiple Doses of 25 mg to 200 mg Once Daily (qd) for 3 Days Assessing Pharmacodynamics as Endotoxin-induced Inflammatory Response of a Single Intravenous Bolus Administration of 2 ng/kg Body Weight Lipopolysaccharide (LPS). A Randomised, Double-blind Within Dose Groups, Placebo-controlled, Multiple Rising Dose Phase I Trial With Open-label Active Comparator in Healthy Male Subjects
The general aim of the current study was to investigate the safety and tolerability, and pharmacodynamics (endotoxin-induced inflammatory response of a single intravenous bolus administration of 2 ng/kg body weight Escherichia coli lipopolysaccharide (LPS)) of BI 653048 BS H3PO4 capsules in healthy male subjects following oral administration of multiple rising doses of 25 mg to 200 mg over three days compared to the active comparator prednisolone and placebo. Pharmacodynamics were assessed by investigating the influence of LPS administration on inflammatory parameters. More specifically, it was evaluated whether and to what extent the symptoms induced by LPS challenge can be attenuated by ascending BI 653048 BS H3PO4 doses using prednisolone as positive control and placebo as negative control. A secondary objective was the exploration of pharmacokinetics of BI 653048 BS, the investigation of other pharmacodynamic parameters (biomarker) and of the tolerability of LPS.
Details
| Lead sponsor | Boehringer Ingelheim |
|---|---|
| Phase | Phase 1 |
| Status | COMPLETED |
| Enrolment | 56 |
| Start date | 2010-03 |
Conditions
- Healthy
Interventions
- BI 653048 BS
- Prednisolone low
- Prednisolone high
- Placebo
- sodium chloride infusion
- endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS)
Primary outcomes
- Number of subjects with adverse events — up to 37 days
- Number of subjects with clinically significant findings in vital signs — up to day 15
blood pressure, pulse rate and body temperature - Number of subjects with clinically significant findings in 12-lead electrocardiogram (ECG) — up to day 15
- Number of subjects with clinically significant findings in laboratory tests — up to day 15
- Assessment of tolerability by investigator on a 4-point scale — up to day 15
- Maximum measured concentration of the biomarker level in plasma (Emax) — up to 96 hours after first drug administration