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
Overview
- Phase
- Phase 1
- Intervention
- BIRT 2584 XX - single dose
- Conditions
- Healthy
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 74
- Primary Endpoint
- Number of subjects with clinically significant changes in 12-lead ECG
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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)
Investigators
Eligibility Criteria
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)
Arms & Interventions
BIRT 2584 XX - single dose
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
Intervention: BIRT 2584 XX - single dose
BIRT 2584 XX - single dose
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
Intervention: high caloric meal
Placebo
Part 2
Intervention: Placebo
BIRT 2584 XX - multiple escalating dose
Part 2 - multiple escalating dose, 14 days and 28 days
Intervention: BIRT 2584 XX - multiple escalating dose
Outcomes
Primary Outcomes
Number of subjects with clinically significant changes in 12-lead ECG
Time Frame: up to 45 days
Number of subjects with abnormal findings in physical examination
Time Frame: up to 45 days
Number of subjects with abnormal changes in laboratory parameters
Time Frame: up to 45 days
Number of subjects with clinically significant changes in vital signs
Time Frame: up to 45 days
Pulse rate, systolic, and diastolic blood pressure
Number of subjects with adverse events
Time Frame: up to 59 days
Secondary Outcomes
- Cmax (maximum concentration of BIRT 2584 XX and BI 610100 in plasma)(up to 42 days)
- CL/F,ss (apparent clearance of BIRT 2584 XX from plasma at steady state after extravascular multiple dose administration)(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)(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)(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)(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)(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)(up to 42 days)
- tmax (time from dosing to maximum concentration of BIRT 2584 XX and BI 610100, its major metabolite in humans)(up to 72 hours)
- tmax (time from dosing to maximum concentration of BIRT 2584 XX and BI 610100)(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(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)(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)(up to 42 days)
- AUC0-inf (area under the concentration-time curve of BIRT 2584 XX in plasma over the time interval from 0 to infinity)(up to 72 hours)
- Cmax (maximum concentration of BIRT 2584 XX in plasma)(up to 72 hours)
- Assessment of receptor occupancy(up to 42 days)
- Assessment of ex vivo suppression of superantigen (SEB)-induced Interleukin (IL)-2 production(up to 42 days)
- t1/2,ss (terminal half-life of BIRT 2584 XX and BI 610100 in plasma at steady state)(up to 42 days)
- Total number of white blood cells and leukocyte differential cell count(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)(up to 42 days)
- λz,ss (terminal rate constant of BIRT 2584 XX and BI 610100 in plasma at steady state)(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)(up to 42 days)