Safety and Tolerability of 4 Different Dosage Strengths of BIBW 2992 Tablets to Healthy Male Volunteers

Pharmacokinetics, Safety and Tolerability of BIBW 2992 Administered Orally as 20 mg, 30 mg, 40 mg, and 50 mg Tablets (Final Formulation) to Healthy Male Volunteers in an Open-label, Single Rising Dose, Phase I Trial

Study to assess pharmacokinetics incl. dose proportionality, safety and tolerability of 4 different dosage strengths of BIBW 2992 tablets (final formulation of 20 mg, 30 mg, 40 mg, 50 mg) administered as single doses to healthy male volunteers

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BIBW 2992 MA2 - single rising dose

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males according to a complete medical history, including a physical examination, vital signs (blood pressure, pulse rate), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
• Age 21 to 55 years, inclusive
• Body mass index 18.5 to 29.9 kg/m2, inclusive
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Exclusion Criteria:

• Any finding of the medical examination (including Blood Pressure (BP), Puse Rate (PR) and Electrocardiogram (ECG)) deviating from normal and of clinical relevance
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including drug allergy or its excipients)
• Intake of drugs with a long half-life (>24 hours) within 1 month prior to administration of the trial drug or during the trial
• Use of any drugs (including herbal preparations, vitamins and nutrient supplements) within 10 days prior to administration of the trial drug 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)
• Inability to refrain from smoking within the in-house periods from 12 hours before until 25 hours after each administration of the trial drug
• Alcohol abuse (more than 30 g/day)
• Drug abuse
• Blood donation (more than 100 mL within 4 weeks prior to administration of the trial drug or during the trial)
• Excessive physical activities (within 1 week prior to administration of the trial drug or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
• A history of additional risk factors for Torsades de Points, e.g., heart failure, hypokalemia, family history of Long QT Syndrome

Exclusion criteria specific for this study:

• History of clinically relevant skin diseases, psoriasis or moderate/severe acne
• History or evidence of interstitial lung disease
• Males who are unwilling to use a medically acceptable method of contraception during the first 3 months after administration of the trial drug. Acceptable methods of contraception for use by male volunteers include sexual abstinence, a vasectomy performed at least 1 year prior to dosing, barrier contraception or another medically accepted contraceptive method

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIBW 2992 MA2 - single rising dose	Drug: BIBW 2992 MA2 - single rising dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum measured concentration of the analyte in plasma)	predose, up to120 h after drug administration
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)	predose, up to 120 h after drug administration
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)	predose, up to 120 h after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
%AUCtz-∞ (percentage of the AUCtz-∞ obtained by extrapolation from the last quantifiable data point to infinity)	predose, up to 120 h after drug administration
AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 [predose] to 24 h)	predose, up to 120 h after drug administration
tmax (time from dosing to the maximum concentration of the analyte in plasma)	predose, up to 120 h after drug administration
λz (terminal rate constant of the analyte in plasma)	predose, up to 120 h after drug administration
t1/2 (terminal half-life of the analyte in plasma)	predose, up to 120 h days after drug administration
MRTpo (mean residence time of the analyte in the body after oral administration)	predose, up to 120 h after drug administration
CL/F (apparent clearance of the analyte in plasma after extravascular administration)	predose, up to 120 h after drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)	predose, up to 120 h after drug administration
Number of patients with abnormal findings in physical examination	Screening, up to 20 days after drug administration
Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate)	Screening, up to 20 days after drug administration
Number of patients with abnormal changes in laboratory parameters	Screening, up to 20 days after drug administration
Number of patients with adverse events	up to 41 days
Assessment of tolerability by investigator on a 4-point scale	up to 20 days after drug administration
Number of patients with abnormal changes in 12-lead electrocardiogram (ECG)	Screening, up to 20 days after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Estimate): June 24, 2014
• Last Update Submitted That Met QC Criteria: June 20, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: 1200.80