Metabolism and Pharmacokinetics of Oral Solution of [14C]-BI 201335 in Healthy Male Volunteers

NCT02182349 | Completed Phase 1

• 1 other identifier: 1220.33
• Study Type: interventional
• Target: 8
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study to determine the pharmacokinetics (PK) of BI 201335 and total radioactivity including excretion mass balance, excretion pathways and metabolism following the oral administration of \[14C\]-BI 201335 at steady state.

Conditions

Healthy

Outcome Measures

Primary Outcomes (20)

• Individual concentration-time profiles of [14C]-radioactivity in whole blood, plasma, saliva, urine, and faeces

  up to 28 days

• Individual concentration-time profiles of BI 201335 ZW in plasma and urine

  up to 28 days

• Rate and extent of excretion mass balance based on the total radioactivity in urine and faeces

  up to 28 days

• Elucidation of metabolite structures and identification of major metabolites in urine, faeces, and plasma in comparison with various animal species

  up to 28 days

• Cblood cell/Cplasma ratio of [14C]-radioactivity

  up to 28 days

• Measurement of the plasma protein binding of total [14C]-radioactivity in human plasma samples ex vivo

  up to day 28

• Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)

  up to day 28

• tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state)

  up to day 28

• Cmin,ss (minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ)

  up to day 28

• AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ)

  up to day 28

• λz,ss (terminal rate constant of the analyte in plasma at steady state)

  up to day 28

• t1/2,ss (terminal half-life of the analyte in plasma at steady state)

  up to day 28

• MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)

  up to day 28

• CL/F,ss (apparent clearance of the analyte in the plasma at steady state following multiple oral dose administration)

  up to day 28

• Vz/F,ss (apparent volume of distribution of the analyte during the terminal phase λz at steady state following oral administration)

  up to day 28

• Ae,urine,0-tz,ss (amount of analyte that is eliminated in urine at steady state from the time point 0 to time point tz)

  up to day 28

• fe,urine,t1-t2,ss (fraction of the analyte in % of dose that is eliminated in urine at steady state from the time point 0 to time point tz)

  up to day 28

• Ae,feces,t1-t2,ss (fraction of the analyte that is eliminated in faeces at steady state from time point 0 to time point tz)

  up to day 28

• fe,feces,0-tz,ss (fraction of the analyte eliminated in faeces at steady state from time point 0 to time point tz)

  up to day 28

• CLR,t1-t2,ss (renal clearance of the analyte at steady state from the time point 0 to time point tz)

  up to day 28

Secondary Outcomes (6)

• Number of patients with abnormal findings in physical examination

  Baseline and day 28

• Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate)

  Baseline, day 1, 10, 16 and 28

• Number of patients with clinically significant changes in 12-lead electrocardiogram (ECG)

  Baseline, day 1, 10, 16 and 28

• Number of patients with clinically significant changes in clinical laboratory tests (haematology, clinical chemistry, urinalysis)

  Baseline, day 10 and 28

• Number of patients with adverse events

  up to 28 days

Study Arms (1)

BI 201335 NA

EXPERIMENTAL

multiple doses of BI 201335 NA soft gelatin capsule on days 1-8 and 11-15 and one single dose of \[14C\]-BI 201335 NA radiolabelled drug on day 9

Drug: BI 201335 NA soft gelatin capsule; Drug: [14C]-BI 201335 NA radiolabelled drug

Interventions

BI 201335 NA soft gelatin capsule DRUG

BI 201335 NA

[14C]-BI 201335 NA radiolabelled drug DRUG

BI 201335 NA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males according to a complete medical history, including a physical examination, vital signs (blood pressure, pulse rate), 12-lead ECG (electrocardiogram), and clinical laboratory tests
• Age 18 to 55 years, inclusive
• Body mass index 18.5 to 29.9 kg/m2, inclusive
• Nonsmoker
• Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation

You may not qualify if:

• Any finding in the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal, psychiatric or neurological disorders (including all forms of epilepsy)
• Surgery of the gastrointestinal tract (except appendectomy)
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Subjects with Gilbert's Syndrome
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs with a long half-life (\>24 hours) within one month prior to administration of the trial drug
• Use of prescription medication, over-the-counter drugs or herbal preparations within 14 days prior to administration of the trial drug
• Participation in another trial with an investigational drug within two months prior to administration of the trial drug or during the trial
• History or evidence of habitual tobacco or nicotine use within six months prior to administration of the trial drug
• Alcohol abuse (more than 2 ounces of alcohol/day)
• Drug abuse in opinion of investigator
• Blood donation (more than 100 mL within four weeks prior to administration of trial drug or during the trial)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 8, 2014
• Study Start: June 1, 2009
• Primary Completion: July 1, 2009
• Last Updated: July 18, 2014

Record last verified: 2014-07