Healthy
Conditions
Brief summary
The primary objective of this trial is to investigate the safety and tolerability of multiple doses of BI 655064 following weekly subcutaneous injection for 4 weeks in healthy Chinese male volunteers. The secondary objective is the exploratory evaluation of the pharmacokinetics and pharmacodynamics of multiple doses of BI 655064 following weekly subcutaneous injection for 4 weeks in healthy Chinese male volunteers.
Interventions
DRUGBI 655064
subcutaneous injection
DRUGPlacebo
Placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males according to the investigator's assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (Blood pressure, Pulse rate), 12-lead Echocardiogram, and clinical laboratory tests 2. Chinese ethnicity according to the following criteria: Ethnic 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 3. Age within the range of 20 to 45 years inclusive 4. Body Mass Index within the range of 18.5 and 25 kg/m2 inclusive 5. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation 6. Male subjects who * are documented to be sterile or consistently and correctly use a condom while their female partners (if of childbearing potential) agree to use any of the following adequate contraception methods: implants, injectables, combined oral contraceptives, intrauterine device (IUD) from the date of screening until at least 6 months after the last dose of BI 655064 taken in the current trial. * do not donate any sperm sample for procreation purposes, from the date of screening until at least 6 months after last dose of BI 655064 taken in the current trial. It is the responsibility of the male subject to ensure that his partner does not become pregnant during all the study duration.
Exclusion criteria
1. Any finding in the medical examination (including Blood pressure, Pulse rate or Echocardiogram) deviating from normal and judged clinically relevant by the investigator 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. Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders 6. History of relevant orthostatic hypotension, fainting spells, or blackouts 7. History of relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients) 8. Intake of drugs with a long half-life (\>24 hours) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication 9. Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial 10. Participation in another trial with investigational drug administration within 60 days prior to administration of trial medication 11. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day) 12. Inability to refrain from smoking on trial days 13. Alcohol abuse (consumption of more than 20 g/day) 14. Drug abuse or positive drug screen 15. Blood donation (more than 100 mL within 30 days prior to administration of trial medication or intended during the trial) 16. Intention to commence new exercise regimen or excessive physical activities within one week prior to administration of trial medication or during the trial 17. Inability to comply with protocol requirements (including dietary regimen of trial site) as assessed by the investigator 18. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of QTc interval \> 450 ms) at screening examination 19. Positive results of infectious serology (Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody or Human Immunodeficiency Virus) at screening examination 20. History of tuberculosis infection and/or positive Quantiferon Tuberculosis-Gold test at screening examination 21. Abnormal results of coagulation values indicating an increased risk for bleeding or thromboembolism or complicating the safety evaluation during the study as determined by the investigator at screening examination 22. Subjects who in the investigator's judgement are perceived as having an excessive risk of thromboembolism for example because of a personal history and/or a first degree relative with a personal history with onset under the age of 55 of significant thromboembolism, including but not limited to deep vein thrombosis, pulmonary embolism, cortical sinus thrombosis, coronary and cerebrovascular events, and peripheral arterial insufficiency. 23. Deficiency of antithrombin III or protein S or protein C at screening examination 24. Prolongation of bleeding time out of reference range at screening examination 25. Subject is assessed by the investigator as unsuitable for inclusion e.g. considered not able to understand and comply with study requirements or has a condition that would not allow safe participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Drug-related Adverse Events. | From the first drug administration until 126 days after last drug administration, up to 148 days. | Percentage of subjects with drug-related adverse events (AEs). Medical judgment was used to determine the relationship between study medication and AEs, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Dosing to Maximum Measured Concentration of BI 655064 in Plasma After the 1st Dose (Tmax) | Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h after first drug administration on day 1. | Time from dosing to maximum measured concentration of BI 655064 in plasma after the 1st dose (tmax). |
| Area Under the Concentration-time Curve of BI 655064 in Plasma After the 1st Dose Over a Uniform Dosing Interval τ (AUCτ,1) | Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h after first drug administration on day 1. | Area under the concentration-time curve of BI 655064 in plasma after the 1st dose over a uniform dosing interval τ (= 1 week) (AUCτ,1). |
| Maximum Measured Concentration of BI 655064 in Plasma After the 4th Dose (Cmax,4) | Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22. | Maximum measured concentration of BI 655064 in plasma after the 4th dose (Cmax,4). |
| Maximum Measured Concentration of BI 655064 in Plasma After the 1st Dose (Cmax) | Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 hours (h) after first drug administration on day 1. | Maximum measured concentration of BI 655064 in plasma after the 1st dose (Cmax). |
| Area Under the Concentration-time Curve of BI 655064 in Plasma After the 4th Dose Over a Uniform Dosing Interval τ (AUCτ,4) | Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22. | Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval τ (= 1 week) (AUCτ,4). |
| Accumulation Ratio of BI 655064 in Plasma After Administration of the 4th Dose Over the Dosing Interval τ, Expressed as Ratio of Cmax After the 4th Dose and After the 1st Dose (RA,Cmax,4) | Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h for Cmax and 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520, 3192 and 5880 h for Cmax,4. | Accumulation ratio of BI 655064 in plasma after administration of the 4th dose over the dosing interval τ (= 1 week), expressed as ratio of Cmax after the 4th dose and after the 1st dose (RA,Cmax,4). |
| Accumulation Ratio of BI 655064 in Plasma After Administration of the 4th Dose Over the Dosing Interval τ, Expressed as Ratio of AUC After the 4th Dose and After the 1st Dose (RA,AUC,4) | Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h for AUCτ,1 and 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520, 3192 and 5880 h for AUCτ,4. | Accumulation ratio of BI 655064 in plasma after administration of the 4th dose over the dosing interval τ (= 1 week), expressed as ratio of AUC after the 4th dose and after the 1st dose (RA,AUC,4). |
| Time From Dosing to Maximum Measured Concentration of BI 655064 in Plasma After the 4th Dose (Tmax,4) | Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22. | Time from dosing to maximum measured concentration of BI 655064 in plasma after the 4th dose (tmax,4). |
Countries
South Korea
Participant flow
Recruitment details
This was a randomised, double-blind, placebo-controlled, multiple dose trial.
Pre-assignment details
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks. | 3 |
| BI 655064 Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks. | 9 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | BI 655064 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 25.1 Years STANDARD_DEVIATION 3.41 | 26.1 Years STANDARD_DEVIATION 3.87 | 29.0 Years STANDARD_DEVIATION 4.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 12 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 12 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 12 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 9 |
| other Total, other adverse events | 3 / 3 | 6 / 9 |
| serious Total, serious adverse events | 0 / 3 | 0 / 9 |
Outcome results
Primary
Percentage of Subjects With Drug-related Adverse Events.
Percentage of subjects with drug-related adverse events (AEs). Medical judgment was used to determine the relationship between study medication and AEs, considering all relevant factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, confounding factors such as concomitant medication, concomitant diseases and relevant history.
Time frame: From the first drug administration until 126 days after last drug administration, up to 148 days.
Population: Treated set (TS): This set included all subjects who were dispensed study medication and were documented to have received at least 1 dose of investigational treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Subjects With Drug-related Adverse Events. | 66.7 Percentage of subjects |
| BI 655064 | Percentage of Subjects With Drug-related Adverse Events. | 55.6 Percentage of subjects |
Secondary
Accumulation Ratio of BI 655064 in Plasma After Administration of the 4th Dose Over the Dosing Interval τ, Expressed as Ratio of AUC After the 4th Dose and After the 1st Dose (RA,AUC,4)
Accumulation ratio of BI 655064 in plasma after administration of the 4th dose over the dosing interval τ (= 1 week), expressed as ratio of AUC after the 4th dose and after the 1st dose (RA,AUC,4).
Time frame: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h for AUCτ,1 and 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520, 3192 and 5880 h for AUCτ,4.
Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Accumulation Ratio of BI 655064 in Plasma After Administration of the 4th Dose Over the Dosing Interval τ, Expressed as Ratio of AUC After the 4th Dose and After the 1st Dose (RA,AUC,4) | 4.19 Ratio of AUC after the 4th and 1st dose | Geometric Coefficient of Variation 32.9 |
Secondary
Accumulation Ratio of BI 655064 in Plasma After Administration of the 4th Dose Over the Dosing Interval τ, Expressed as Ratio of Cmax After the 4th Dose and After the 1st Dose (RA,Cmax,4)
Accumulation ratio of BI 655064 in plasma after administration of the 4th dose over the dosing interval τ (= 1 week), expressed as ratio of Cmax after the 4th dose and after the 1st dose (RA,Cmax,4).
Time frame: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h for Cmax and 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520, 3192 and 5880 h for Cmax,4.
Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Accumulation Ratio of BI 655064 in Plasma After Administration of the 4th Dose Over the Dosing Interval τ, Expressed as Ratio of Cmax After the 4th Dose and After the 1st Dose (RA,Cmax,4) | 3.24 Ratio of Cmax after the 4th and 1st dose | Geometric Coefficient of Variation 24.8 |
Secondary
Area Under the Concentration-time Curve of BI 655064 in Plasma After the 1st Dose Over a Uniform Dosing Interval τ (AUCτ,1)
Area under the concentration-time curve of BI 655064 in plasma after the 1st dose over a uniform dosing interval τ (= 1 week) (AUCτ,1).
Time frame: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h after first drug administration on day 1.
Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 655064 in Plasma After the 1st Dose Over a Uniform Dosing Interval τ (AUCτ,1) | 2610 μg*h/mL | Geometric Coefficient of Variation 79 |
Secondary
Area Under the Concentration-time Curve of BI 655064 in Plasma After the 4th Dose Over a Uniform Dosing Interval τ (AUCτ,4)
Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval τ (= 1 week) (AUCτ,4).
Time frame: Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22.
Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve of BI 655064 in Plasma After the 4th Dose Over a Uniform Dosing Interval τ (AUCτ,4) | 10900 μg*h/mL | Geometric Coefficient of Variation 49.9 |
Secondary
Maximum Measured Concentration of BI 655064 in Plasma After the 1st Dose (Cmax)
Maximum measured concentration of BI 655064 in plasma after the 1st dose (Cmax).
Time frame: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 hours (h) after first drug administration on day 1.
Population: The pharmacokinetic (PK) set (PKS): This set included all evaluable subjects in TS who provided at least 1 PK parameter. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 655064 in Plasma After the 1st Dose (Cmax) | 22.9 microgram (μg) / milliLitre (mL) | Geometric Coefficient of Variation 72.3 |
Secondary
Maximum Measured Concentration of BI 655064 in Plasma After the 4th Dose (Cmax,4)
Maximum measured concentration of BI 655064 in plasma after the 4th dose (Cmax,4).
Time frame: Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22.
Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Measured Concentration of BI 655064 in Plasma After the 4th Dose (Cmax,4) | 74.1 μg/mL | Geometric Coefficient of Variation 50.4 |
Secondary
Time From Dosing to Maximum Measured Concentration of BI 655064 in Plasma After the 1st Dose (Tmax)
Time from dosing to maximum measured concentration of BI 655064 in plasma after the 1st dose (tmax).
Time frame: Pharmacokinetic samples were collected at -3, 8, 12, 24, 48, 72, 84, 96, 108, 120, 144 and 167.5 h after first drug administration on day 1.
Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time From Dosing to Maximum Measured Concentration of BI 655064 in Plasma After the 1st Dose (Tmax) | 132 hours (h) |
Secondary
Time From Dosing to Maximum Measured Concentration of BI 655064 in Plasma After the 4th Dose (Tmax,4)
Time from dosing to maximum measured concentration of BI 655064 in plasma after the 4th dose (tmax,4).
Time frame: Pharmacokinetic samples were collected at 505, 516, 528, 552, 576, 600, 624, 648, 672, 696, 744, 816, 912, 1008, 1176, 1344, 1512, 1848, 2520 and 3192 h after fourth drug administration on day 22.
Population: PKS. One subject was excluded from the PKS as he developed a positive anti-BI 655064 antibodies response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time From Dosing to Maximum Measured Concentration of BI 655064 in Plasma After the 4th Dose (Tmax,4) | 84.2 h |