Clinical trial NCT01348165: Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 137882 in Healthy Male Volunteers
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-05-05
Enrollment: 40
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

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 (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)

Primary outcomes:
measure: Number of Subjects With Drug Related Adverse Events
timeFrame: From baseline up to 28 days
measure: Blood Pressure
timeFrame: Baseline and 28 days
measure: Pulse Rate (PR)
timeFrame: Baseline and 28 days
measure: Respiratory Rate (RR)
timeFrame: Baseline and 28 days
measure: Body Temperature
timeFrame: Baseline and 28 days
measure: Assessment of Tolerability by Investigator
timeFrame: 28 days
Secondary outcomes:
measure: Maximum Measured Concentration (Cmax)
timeFrame: 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
measure: Time to Maximum Measured Concentration (Tmax)
timeFrame: 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
measure: Area Under the Curve 0 to Infinity (AUC0-infinity)
timeFrame: 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
measure: Terminal Half-life (t1/2)
timeFrame: 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
measure: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
timeFrame: 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
measure: Terminal Rate Constant (λz)
timeFrame: 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
measure: Mean Residence Time (MRTpo)
timeFrame: 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
measure: Apparent Clearance (CL/F)
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: 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
measure: Amount of BI 137882 Eliminated in Urine From the Time Point t1 to Time Point t2
timeFrame: 0-4, 4-8, 8-12, and 12-24 hours after drug administration
measure: Fraction of BI 137882 Eliminated in Urine From Time Point t1 to Time Point t2
timeFrame: 0-4, 4-8, 8-12, and 12-24 hours after drug administration
measure: Renal Clearance of BI 137882 From the Time Point t1 Until the Time Point t2
timeFrame: 0-4, 4-8, 8-12, and 12-24 hours after drug administration
measure: Concentration of Tumour Necrosis Factor-alpha (TNF-α) Induced by Lipopolysaccharide (LPS) in Whole Blood ex Vivo
timeFrame: 0.5 hours (h) before drug administration and 2h, 6h, 24h and 48h after drug administration
measure: Concentration of Leukotriene B4 (LTB4) Induced by N-formyl-methionine-leucine-phenylalanine (fMLP) in Whole Blood ex Vivo.
timeFrame: 0.5 hours (h) before drug administration and 2h, 6h, 24h and 48h after drug administration
measure: Area Under the Effect Curve (AUEC)
timeFrame: 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration
measure: Maximum Effect (Emax)
timeFrame: 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration
measure: Minimum Effect (Emin)
timeFrame: 30 minutes (min) before drug administration and 2 hours (h), 6h, 24h and 48h after drug administration
Other outcomes:
Locations:
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: