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

NCT ID: NCT02224105

Last Updated: 2014-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31

Brief Summary

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

BI 653048 BS

escalating doses

Group Type: EXPERIMENTAL

BI 653048 BS

Intervention Type: DRUG

sodium chloride infusion

Intervention Type: DRUG

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

Intervention Type: DRUG

Prednisolone low

Group Type: ACTIVE_COMPARATOR

Prednisolone low

Intervention Type: DRUG

sodium chloride infusion

Intervention Type: DRUG

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

Intervention Type: DRUG

Prednisolone high

Group Type: ACTIVE_COMPARATOR

Prednisolone high

Intervention Type: DRUG

sodium chloride infusion

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

sodium chloride infusion

Intervention Type: DRUG

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

Intervention Type: DRUG

Interventions

BI 653048 BS

Intervention Type: DRUG

Prednisolone low

Intervention Type: DRUG

Prednisolone high

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

sodium chloride infusion

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Harcken C, Scholl P, Nabozny G, Thomson D, Bianchi D. Clinical profile of the functionally selective glucocorticoid receptor agonist BI 653048 in healthy male subjects. Expert Opin Investig Drugs. 2019 May;28(5):489-496. doi: 10.1080/13543784.2019.1599859. Epub 2019 Apr 9.

Reference Type: DERIVED

PMID: 30908082 (View on PubMed)

Other Identifiers

1262.9

Identifier Type: -

Identifier Source: org_study_id