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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: BIRT 2584 XX - single dose; Drug: BIRT 2584 XX - multiple escalating dose; Drug: Placebo; Other: high caloric meal

• Registration Number: NCT02256761
• Lead Sponsor: Boehringer Ingelheim

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)

Detailed Description

Not available

Study Timeline

• Study Start: 2005-01
• Primary Completion: 2005-07
• Status Verified: 2014-10
• Study First Submitted: 2014-10-02
• Study First Submitted QC: 2014-10-02
• Last Update Submitted: 2014-10-02
• Study First Posted: 2014-10-06
• Last Update Posted: 2014-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 74

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
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
BIRT 2584 XX - single dose	high caloric meal	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
BIRT 2584 XX - multiple escalating dose	BIRT 2584 XX - multiple escalating dose	Part 2 - multiple escalating dose, 14 days and 28 days
Placebo	Placebo	Part 2

Primary Outcome Measures

Name	Time	Method
Number of subjects with clinically significant changes in 12-lead ECG	up to 45 days
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	up to 45 days	Pulse rate, systolic, and diastolic blood pressure
Number of subjects with adverse events	up to 59 days

Secondary Outcome Measures

Name	Time	Method
Cmax (maximum concentration of BIRT 2584 XX and BI 610100 in plasma)	up to 42 days	multiple rising dose part
CL/F,ss (apparent clearance of BIRT 2584 XX from plasma at steady state after extravascular multiple dose administration)	up to 42 days	multiple rising dose part
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	multiple rising dose part
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	multiple rising dose part
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	multiple rising dose part
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	multiple rising dose part
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	multiple rising dose part
tmax (time from dosing to maximum concentration of BIRT 2584 XX and BI 610100, its major metabolite in humans)	up to 72 hours	bioavailability/food effect part
tmax (time from dosing to maximum concentration of BIRT 2584 XX and BI 610100)	up to 42 days	multiple rising dose part
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	multiple rising dose part
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	multiple rising dose part
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	multiple rising dose part
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	bioavailability/food effect part
Cmax (maximum concentration of BIRT 2584 XX in plasma)	up to 72 hours	bioavailability/food effect part
Assessment of receptor occupancy	up to 42 days	determined by a competitive binding assay using anti-Lymphocyte function associated antigen-1 (LFA-1) antibody fragment as competitor
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
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	multiple rising dose part
λz,ss (terminal rate constant of BIRT 2584 XX and BI 610100 in plasma at steady state)	up to 42 days	multiple rising dose part
t1/2,ss (terminal half-life of BIRT 2584 XX and BI 610100 in plasma at steady state)	up to 42 days	multiple rising dose part
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	multiple rising dose part