Single Rising Dose Study of BI 201335 ZW in Healthy Male Subjects

Safety, Tolerance, and Pharmacokinetics of Single Oral Doses of 5 mg, 20 mg, 60 mg, 150 mg, 300 mg, 600 mg, 1000 mg, and 1500 mg BI 201335 ZW (PEG 400/TRIS/Water Solution) in Healthy Male Subjects, in a Randomised Double Blind, Placebo Controlled Rising Dose Study, Followed With an Open-label Intra-subject Two-stage Crossover Pilot Bioavailability Comparison of 600 mg BI 201335 ZW in a PEG 400/TRIS/Water Solution Co-administered With Food

The objective of the current study is to investigate safety, tolerability, and pharmacokinetics of BI 201335 ZW following administration of single rising doses from 5 mg to 1500 mg. In addition Two stage intra-subject bioavailability comparison of 600 mg BI 201335 ZW as a liquid formulation given with and without food.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 201335 ZW - single rising dose

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males according to the following criteria based upon a complete medical history, including the physical examination, vital signs ((blood pressure (BP), pulse rate (HR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
• Age ≥18 and Age ≤55 years
• BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation
• Willingness to abstain from alcohol from screening period until conclusion visit

Exclusion Criteria:

• Any finding of 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
• History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders, including a clinical history of viral hepatitis, or serological evidence of active Hepatitis B or Hepatitis C infection
• History of orthostatic hypotension, fainting spells and blackouts
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Intake of drugs with a long half-life (> 24 hours) within 1 month prior to administration
• Use of any drugs which might influence the results of the trial within 10 days prior to administration or during the trial
• Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
• Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on trial days
• Alcohol abuse (> 60 g/day)
• Drug abuse
• Blood donation within 1 month prior to administration or during the trial
• Excessive physical activities within 5 days prior to administration or during the trial
• Any laboratory value outside the clinically accepted reference range and of clinical relevance
• History of any familial bleeding disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: BI 201335 ZW - single rising dose	Drug: BI 201335 ZW - single rising dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with abnormal findings in physical examination	Baseline, day 3 of each treatment period, within 8 days after last administration
Number of patients with clinically significant changes in vital signs	Baseline, day 1-3 of each treatment period, within 8 days after last administration
Number of patients with clinically significant changes in 12-lead ECG (electrocardiogram)	Baseline, day 1, 2 in treatment period, within 8 days after last administration
Number of patients with abnormal changes in laboratory parameters	Baseline, day 1-3 of each treatment period, within 8 days after last administration
Number of patients with adverse events	up to 13 days
Assessment of tolerability by investigator on a 4-point scale	on day 3 of each treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum concentration of the analyte in plasma)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose
tmax (time from dosing to maximum concentration)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose
AUC0-∞ (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose
λz (terminal elimination rate constant in plasma)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose
t1/2 (terminal half-life of the analyte in plasma)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose
MRTpo (Mean residence time of the analyte in the body after oral administration)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose
CL/F (apparent clearance of the analyte in the plasma after oral administration)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose
Vz/F (apparent volume of distribution during the terminal phase λz following an oral dose)	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): October 1, 2004
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: July 2, 2014
• First Submitted That Met QC Criteria: July 7, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 1220.1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No