Clinical trial NCT02057835: Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 691751 in Healthy Asian Male Volunteers
Official title: Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 691751 in Healthy Asian Male Volunteers in a Randomised, Double-blind, Placebo-controlled Design.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-02-07
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: BI 691751 is currently being developed to inhibit growth and prevent rupture of atherosclerotic plaques and to consequently reduce the risk of major cardiovascular events in patients with established atherosclerotic disease. 1334.5 is a Pan Asian Phase 1 study to investigate safety, tolerability and pharmacokinetics of BI 691751 in healthy Chinese and Japanese male volunteers.


Eligibility criteria: Inclusion criteria:

1. Healthy males based upon a complete medical history, including a physical examination, vital signs (blood pressure, pulse rate), 12-lead ECG, and clinical laboratory tests
2. Chinese ethnicity, Japanese ethnicity according to the following criteria:

   Chinese; born in China or ethnic Chinese born outside of China, and a descendent of 4 ethnic Chinese grandparents who were all born in China Japanese; born in Japan and holding Japanese passport, have lived outside of Japan \<10 years, and have parents and grandparents who were all born in Japan
3. Age within the range of 20 to 45 years
4. Body mass index within the range of 18.5 and 25 kg/m2
5. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation.

Exclusion criteria:

1. Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator. Pulse rate outside the range of 50-90 bpm or blood pressure outside the ranges of 90-140 for systolic and 50-90 mmHg for diastolic blood pressure if confirmed by repeat measurement.
2. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
3. Any evidence of a concomitant disease judged clinically relevant by the investigator
4. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
5. Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug
6. Diseases of the central nervous system (such as epilepsy), central neurological disorders or psychiatric disorders
7. History of relevant orthostatic hypotension, fainting spells, or blackouts
8. Relevant chronic or acute infections
9. History of relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients)
10. Intake of drugs with a long half-life (greater than 24 hours) within 30 days or less than 10 half-lives of the respective drug prior to study drug administration
11. Use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTc interval within 14 days prior to study drug administration
12. Participation in another trial with investigational drug administration within 60 days prior to administration of trial medication
13. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day)
14. Inability to refrain from smoking on specified trial days
15. Alcohol abuse (consumption of more than30 g/day)
16. Drug abuse or positive drug screen
17. Blood donation (more than 100 mL within 30 days prior to administration of trial medication or intended during the trial)
18. Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
19. Inability to comply with dietary regimen of trial site
20. A marked baseline prolongation of QT/QTc interval (such as repeated demonstration of a QTc interval greater than 450 ms) or any other relevant ECG finding
21. A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
22. Subject is assessed by the investigator as unsuitable for inclusion, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study.

Primary outcomes:
measure: Percentage of Participants With Drug Related Adverse Events
timeFrame: From drug administration until 31 days after drug administration, 31 days
Secondary outcomes:
measure: Maximum Measured Concentration of the Analyte (Cmax)
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Maximum Measured Concentration of the Analyte (Cmax) - Overall
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax)
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz)
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz) - Overall
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Terminal Half-life of the Analyte (T1/2)
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
measure: Terminal Half-life of the Analyte (T1/2) - Overall
timeFrame: 1 hour (h) before drug administration and 20minutes (min), 40min, 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 192h, 240h, 288h and 336h after drug administration
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: 1334.5.82001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: