Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 137882 in Healthy Male Volunteers

Healthy Clinical Trial

Official title:

Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 137882 in Healthy Male Volunteers (A Randomised, Single-blind, Placebo-controlled Phase I Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01348165
• Other study ID #: 1306.1
• Secondary ID: 2010-023462-52
• Status: Terminated
• Phase: Phase 1
• First received: May 3, 2011
• Last updated: June 18, 2014
• Start date: May 2011

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 137882 in Healthy Male Volunteers

Description:

As a transition from preclinical investigations to clinical development in this first-in-man trial, safety, tolerability, and pharmacokinetics of BI 137882 will be assessed in healthy male volunteers using single rising oral doses in order to provide the basis for a potential ongoing clinical development of BI 137882 in the indication of COPD.

Healthy male subjects aged 21 - 50 years will be recruited for this study. They provide a relatively stable physiological, biochemical and hormonal basis (steady state) for studying drug effects, they show no disease-related variation and they are not taking concomitant medication.

Within each dose group, all actively treated individuals will receive the same BI 137882 dose. The next higher dose will only be administered if the treatment in the preceding dose group was safe and well tolerated.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 21 Years to 50 Years

Eligibility

Inclusion criteria:

1. Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests

2. Age 21 to 50 years

3. BMI 18.5 to 29.9 kg/m2 (Body Mass Index)

4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

Exclusion criteria:

1. Any finding of the medical examination (including BP, PR 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 two months prior to administration or during the trial

12. Smoker (more than 10 cigarettes /day)

13. Inability to refrain from smoking on trial days

14. Alcohol abuse (more than 20 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

20. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms);

21. A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• BI 137882
Medium dose powder for oral solution
• BI 137882
High dose powder for oral solution
• Placebo
Powder for oral solution
• BI 137882
Low dose powder for oral solution

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Drug Related Adverse Events	Number of subjects with drug related adverse events (AEs)	From baseline up to 28 days	No
Primary	Blood Pressure	Change from baseline for systolic blood pressure (SBP) and diastolic blood pressure (DBP)	Baseline and 28 days	No
Primary	Pulse Rate (PR)	Change from Baseline to 28 Days in Pulse Rate	Baseline and 28 days	No
Primary	Respiratory Rate (RR)	Change from Baseline to 28 Days in Respiratory rate (RR)	Baseline and 28 days	No
Primary	Body Temperature	Change from baseline to 28 Days in Body temperature	Baseline and 28 days	No
Primary	Assessment of Tolerability by Investigator	The investigator assessed tolerability based on adverse events and the laboratory evaluation according to the categories 'good', 'satisfactory', 'not satisfactory', and 'bad'.	28 days	No
Secondary	Maximum Measured Concentration (Cmax)	Maximum measured concentration of BI 137882 in plasma.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Time to Maximum Measured Concentration (Tmax)	Time from dosing to maximum measured concentration of the analyte in plasma.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Area Under the Curve 0 to Infinity (AUC0-infinity)	Area under the concentration-time curve of BI 137882 in plasma over the time interval from 0 extrapolated to infinity.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Terminal Half-life (t1/2)	Terminal half-life of BI 137882 in plasma.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)	Area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Terminal Rate Constant (?z)	Terminal rate constant in plasma.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Mean Residence Time (MRTpo)	Mean residence time of the analyte in the body after oral administration.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Apparent Clearance (CL/F)	Apparent clearance of the analyte in plasma after extravascular administration.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Apparent Volume of Distribution (Vz/F)	Apparent volume of distribution of the analyte during the terminal phase.	30 minutes (min) before drug administration and 30min, 1 hour (h), 2h, 4h, 6h, 8h, 12h, 24h, 34h, 48h, 72h, 96h, 144h, 192h, 264h, 336h and 480h after drug administration	No
Secondary	Amount of BI 137882 Eliminated in Urine From the Time Point t1 to Time Point t2	Amount of BI 137882 eliminated in urine from the time point t1 to time point t2 (Aet1-t2)	0-4, 4-8, 8-12, and 12-24 hours after drug administration	No
Secondary	Fraction of BI 137882 Eliminated in Urine From Time Point t1 to Time Point t2	Fraction of BI 137882 eliminated in urine from time point t1 to time point t2 (fet1-t2)	0-4, 4-8, 8-12, and 12-24 hours after drug administration	No
Secondary	Renal Clearance of BI 137882 From the Time Point t1 Until the Time Point t2	Renal clearance of BI 137882 from the time point t1 until the time point t2 (CLR,t1-t2)	0-4, 4-8, 8-12, and 12-24 hours after drug administration	No
Secondary	Concentration of Tumour Necrosis Factor-alpha (TNF-a) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo	Concentrations of TNF-a in plasma were determined by an enzyme-linked immunosorbent assay (ELISA). Concentrations of TNF-a in blood drawn after treatment with BI 137882 were compared with those in pre-dose samples to calculate the percent of inhibition of LPS induction of TNF-a production. Results indicate percent change from baseline of LPS-induced TNF-a production. A positive value indicates inhibition of the production.	0.5 hours (h) before drug administration and 2h, 6h, 24h and 48h after drug administration	No
Secondary	Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo.	Percent of inhibition of fMLP induction of LTB4 production. Concentrations of LTB4 in plasma were determined by an enzyme-linked immunosorbent assay (ELISA). Results indicate percent change from baseline of fMLP induction of LTB4 production. A positive value indicates inhibition of the production.	0.5 hours (h) before drug administration and 2h, 6h, 24h and 48h after drug administration	No
Secondary	Area Under the Effect Curve (AUEC)	Area under the effect curve for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-a/LTB4 production. A positive value indicates inhibition of the production.	30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration	No
Secondary	Maximum Effect (Emax)	Maximum effect for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-a/LTB4 production. A positive value indicates inhibition of the production.	30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration	No
Secondary	Minimum Effect (Emin)	Minimum effect for TNF-alpha induced by LPS and LTB4 induced by fMLP. Results indicate percent change from baseline of TNF-a/LTB4 production. A positive value indicates inhibition of the production.	30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration	No

External Links

•   Link