Safety and Pharmacokinetics of Multiple Doses of BI 655064 in Healthy Chinese Male Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Subcutaneous Doses of BI 655064 in Healthy Chinese Male Volunteers (Randomised, Double-blind, Placebo-controlled, Clinical Phase I Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 655064
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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 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 Age within the range of 20 to 45 years inclusive Body Mass Index within the range of 18.5 and 25 kg/m2 inclusive Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation 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: Any finding in the medical examination (including Blood pressure, Pulse rate or Echocardiogram) deviating from normal and judged clinically relevant by the investigator Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease judged clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders History of relevant orthostatic hypotension, fainting spells, or blackouts History of relevant allergy/hypersensitivity (including allergy to the trial medication or its excipients) 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 Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial Participation in another trial with investigational drug administration within 60 days prior to administration of trial medication Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (consumption of more than 20 g/day) Drug abuse or positive drug screen Blood donation (more than 100 mL within 30 days prior to administration of trial medication or intended during the trial) Intention to commence new exercise regimen or excessive physical activities within one week prior to administration of trial medication or during the trial Inability to comply with protocol requirements (including dietary regimen of trial site) as assessed by the investigator A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of QTc interval > 450 ms) at screening examination Positive results of infectious serology (Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody or Human Immunodeficiency Virus) at screening examination History of tuberculosis infection and/or positive Quantiferon Tuberculosis-Gold test at screening examination 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 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. Deficiency of antithrombin III or protein S or protein C at screening examination Prolongation of bleeding time out of reference range at screening examination 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 655064<br>Subjects received BI 655064 240 milligram (mg) via subcutaneous injection every week, until 4 weeks. | Drug: BI 655064<br>* subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>Subjects received placebo matching to BI 655064 via subcutaneous injection every week, until 4 weeks. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From the first drug administration until 126 days after last drug administration, up to 148 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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. | 
| 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). | 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 (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). | 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. | 
| 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). | 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) | 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. | 
| 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). | 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. | 
| 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). | 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, 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). | 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. |