Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of BI 653048 BS H3PO4 Capsule Assessing Endotoxin-induced Inflammatory Response in Healthy Male Subjects

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Prednisolone high; Drug: Placebo; Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS); Drug: Prednisolone low; Drug: BI 653048 BS; Drug: sodium chloride infusion

Study type: Interventional

Funder types: Industry

Identifiers

NCT02224105

1262.9

Details and patient eligibility

About

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.

Enrollment: 56 patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy males according to the following criteria:

   Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate and body temperature), 12-lead ECG, clinical laboratory tests

2. Age ≥18 and Age ≤50 years

3. Body mass index (BMI) ≥18.5 and BMI ≤29.9 kg/m2

4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Exclusion criteria

1. Any finding of the medical examination (including blood pressure, pulse rate, orthostatic test, body temperature and ECG) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. Surgery of the gastrointestinal tract (except appendectomy)
5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
6. History of relevant orthostatic hypotension, fainting spells or blackouts
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
9. Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
10. Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
11. Participation in another trial with an investigational drug within 30 days prior to administration or during the trial
12. Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
13. Inability to refrain from smoking for 1 day prior to first drug administration until discharge from the study site
14. Alcohol abuse (more than 60 g/day)
15. Drug abuse
16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
17. Excessive physical activities (within one week prior to administration or during the trial)
18. Any laboratory value outside the reference range that is of clinical relevance
19. Inability to comply with dietary regimen of trial site

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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56 participants in 4 patient groups, including a placebo group

BI 653048 BS

Experimental group

Description:

escalating doses

Treatment:

Drug: sodium chloride infusion

Drug: BI 653048 BS

Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS)

Prednisolone low

Active Comparator group

Treatment:

Drug: sodium chloride infusion

Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS)

Drug: Prednisolone low

Prednisolone high

Active Comparator group

Treatment:

Drug: sodium chloride infusion

Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS)

Drug: Prednisolone high

Placebo

Placebo Comparator group

Treatment:

Drug: sodium chloride infusion

Drug: Placebo

Drug: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS)