Safety, Pharmacokinetics, and Pharmacodynamics of BIRT 2584 XX Administered as Multiple Doses and Safety and Pharmacokinetics of BIRT 2584 XX Administered With and Without Food as Single Dose to Healthy Male Volunteers

Study Overview
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Brief Summary
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The study comprised two parts. The objective of the first study period was to assess the safety and pharmacokinetics of 500 mg of BIRT 2584 XX tablets administered with and without food in male healthy volunteers and to determine the relative bioavailability of the BIRT 2584 XX tablet formulation compared by historical comparison to BIRT 2584 XX powder in PEG 400 (U05-2074) (part 1). The second and major phase of the trial was aimed at evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of BIRT 2584 XX (100 mg, 250 mg, and 500 mg bid on the first 2 days and qd on the following 12 days, or 750 mg qd for 28 days) in healthy male subjects (part 2)

Official Title
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Safety, Pharmacokinetics, and Pharmacodynamics of BIRT 2584 XX Administered as Multiple Doses of 100 mg to 750 mg qd for 14 or 28 Days (Randomised, Double-blind Placebo Controlled Design), and Safety and Pharmacokinetics of 500 mg of BIRT 2584 XX Administered With and Without Food as Single Dose (Open, Intra-individual Comparison) to Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIRT 2584 XX - multiple escalating dose
* Drug: Placebo
* Drug: BIRT 2584 XX - single dose
* Other: high caloric meal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects as determined by results of the screening Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Age ≥ 18 and ≤ 63 years BMI ≥ 18.5 and ≤ 29.9 kg/m2 Exclusion Criteria: Any finding during the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hematological, oncological, or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders Relevant history of orthostatic hypotension, fainting spells, or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) considered relevant to the trial as judged by the investigator Intake of drugs with a long half-life (greater than 24 hours) (less than 1 month prior to administration or during the trial) Use of any drugs, which might influence the results of the trial (less than 10 days prior to study drug administration or expected during the trial) Participation in another trial with an investigational drug (less than 2 months prior to administration or expected during trial) Smoker (more than 10 cigarettes/day or more than 3 cigars/day or more than 3 pipes/day) Alcohol abuse (more than 60 g of ethanol per day) Drug abuse Blood donation or loss greater than 400 mL (less than 1 month prior to administration or expected during the trial) Clinically relevant laboratory abnormalities

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 63 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIRT 2584 XX - single dose<br>Part 1 - bioavailability/food effect two single doses, 30 minutes prior to the second drug administration after a one week wash-out period, a standardised high fat, high caloric meal was served | Drug: BIRT 2584 XX - single dose<br> <br> Other: high caloric meal<br>* 30 minutes prior to the second drug administration after a one week wash-out period, a standardised high fat, high caloric meal was served<br>|
| Placebo Comparator: Placebo<br>Part 2 | Drug: Placebo<br> <br> |
| Experimental: BIRT 2584 XX - multiple escalating dose<br>Part 2 - multiple escalating dose, 14 days and 28 days | Drug: BIRT 2584 XX - multiple escalating dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with abnormal findings in physical examination |  | up to 45 days | 
| Number of subjects with abnormal changes in laboratory parameters |  | up to 45 days | 
| Number of subjects with clinically significant changes in vital signs | Pulse rate, systolic, and diastolic blood pressure | up to 45 days | 
| Number of subjects with adverse events |  | up to 59 days | 
| Number of subjects with clinically significant changes in 12-lead ECG |  | up to 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf (area under the concentration-time curve of BIRT 2584 XX in plasma over the time interval from 0 to infinity) | bioavailability/food effect part | up to 72 hours | 
| Cmax (maximum concentration of BIRT 2584 XX in plasma) | bioavailability/food effect part | up to 72 hours | 
| tmax (time from dosing to maximum concentration of BIRT 2584 XX and BI 610100, its major metabolite in humans) | bioavailability/food effect part | up to 72 hours | 
| Cmax (maximum concentration of BIRT 2584 XX and BI 610100 in plasma) | multiple rising dose part | up to 42 days | 
| tmax (time from dosing to maximum concentration of BIRT 2584 XX and BI 610100) | multiple rising dose part | up to 42 days | 
| AUC0-12 (area under the concentration-time curve of BIRT 2584 XX and BI 610100 in plasma over the time interval from 0 to 12 hours after the first dose | multiple rising dose part | up to 14 hours after first drug administration | 
| AUCtau,l (area under the concentration-time curve of BIRT 2584 XX and BI 610100 in plasma over a uniform dose interval tau after administration of the last dose) | multiple rising dose part | up to 42 days | 
| Cmin,ss (minimum concentration of BIRT 2584 XX and BI 610100 in plasma at steady state over a uniform dosing interval tau) | multiple rising dose part | up to 42 days | 
| AUCtau,ss (area under the concentration-time curve of BIRT 2584 XX and BI 610100 in plasma at steady state over a uniform dosing interval tau) | multiple rising dose part | up to 42 days | 
| λz,ss (terminal rate constant of BIRT 2584 XX and BI 610100 in plasma at steady state) | multiple rising dose part | up to 42 days | 
| t1/2,ss (terminal half-life of BIRT 2584 XX and BI 610100 in plasma at steady state) | multiple rising dose part | up to 42 days | 
| MRTpo,ss (mean residence time of BIRT 2584 XX and BI 610100 in the body at steady state after po administration) | multiple rising dose part | up to 42 days | 
| CL/F,ss (apparent clearance of BIRT 2584 XX from plasma at steady state after extravascular multiple dose administration) | multiple rising dose part | up to 42 days | 
| Vz/F,ss (apparent volume of distribution of BIRT XX 2584 during the terminal phase λz at steady state following extravascular administration) | multiple rising dose part | up to 42 days | 
| Aet1-t2,ss (amount of BIRT 2584 XX and BI 610100 that is eliminated in urine at steady state from the time point t1 to time point t2) | multiple rising dose part | up to 30 days | 
| fet1-t2,ss (fraction of BIRT 2584 XX and BI 610100 eliminated in urine at steady state from time point t1 to the time point t2) | multiple rising dose part | up to 30 days | 
| Accumulation ratio of the analyte in plasma at steady state at the end of dosing expressed as a ratio of Cmax after the last dose to Cmax after the first dose (RA,Cmax) | multiple rising dose part | up to 42 days | 
| Accumulation ratio of the analyte in plasma at steady state at the end of dosing expressed as a ratio of AUCtau after the last dose to AUCtau after the first dose (RA,AUC) | multiple rising dose part | up to 42 days | 
| Assessment of receptor occupancy | determined by a competitive binding assay using anti-Lymphocyte function associated antigen-1 (LFA-1) antibody fragment as competitor | up to 42 days | 
| Assessment of ex vivo suppression of superantigen (SEB)-induced Interleukin (IL)-2 production |  | up to 42 days | 
| Total number of white blood cells and leukocyte differential cell count |  | up to 42 days |