Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses of BI 691751 in Healthy Asian Male Volunteers

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo to BI 691751; Drug: BI 691751 low dose 1; Drug: BI 691751 low dose 2; Drug: BI 691751 middle dose; Drug: BI 691751 high dose

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • 1334.5.82001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 691751 low dose 1	Drug: Placebo to BI 691751; Placebo to BI 691751; Drug: BI 691751 low dose 1; BI 691751 low dose 1
Experimental: BI 691751 low dose 2	Drug: Placebo to BI 691751; Placebo to BI 691751; Drug: BI 691751 low dose 2; BI 691751 low dose 2
Experimental: BI 691751 middle dose	Drug: Placebo to BI 691751; Placebo to BI 691751; Drug: BI 691751 middle dose; BI 691751 middle dose
Experimental: BI 691751 high dose	Drug: Placebo to BI 691751; Placebo to BI 691751; Drug: BI 691751 high dose; BI 691751 high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Drug Related Adverse Events	Percentage of participants with drug related adverse events (AEs)	From drug administration until 31 days after drug administration, 31 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Measured Concentration of the Analyte (Cmax)	Maximum measured concentration of the analyte in plasma/whole blood	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
Maximum Measured Concentration of the Analyte (Cmax) - Overall	Maximum measured concentration of the analyte in plasma/whole blood for all participants (Chinese and Japanese)	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
Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax)	Time from (last) dosing to the maximum measured concentration of the analyte in plasma/whole blood	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
Time From Dosing to the Maximum Measured Concentration of the Analyte (Tmax) - Overall	Time from (last) dosing to the maximum measured concentration of the analyte in plasma/whole blood for all participants (Chinese and Japanese)	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
Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)	Area under the concentration-time curve of the analyte in plasma/whole blood over the time interval from 0 extrapolated to infinity (AUC0-infinity)	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
Area Under the Concentration-time Curve of the Analyte Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) - Overall	Area under the concentration-time curve of the analyte in plasma/whole blood over the time interval from 0 extrapolated to infinity for all participants (Chinese and Japanese)	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
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)	Area under the concentration-time curve of the analyte in plasma/whole blood over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz)	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
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	Area under the concentration-time curve of the analyte in plasma/whole blood over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz) for all participants (Chinese and Japanese)	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
Terminal Half-life of the Analyte (T1/2)	Terminal half-life (T1/2) of the analyte in plasma/whole blood	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
Terminal Half-life of the Analyte (T1/2) - Overall	Terminal half-life (T1/2) of the analyte in plasma/whole blood for all participants (Chinese and Japanese)	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: February 6, 2014
• First Submitted That Met QC Criteria: February 6, 2014
• First Posted (Estimate): February 7, 2014

Study Record Updates

• Last Update Posted (Estimate): December 16, 2015
• Last Update Submitted That Met QC Criteria: November 11, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: 1334.5