Clinical trial NCT02171767: Safety and Tolerability of 4 Different Dosage Strengths of BIBW 2992 Tablets to Healthy Male Volunteers
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 48
Sex: MALE
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: predose, up to120 h after drug administration
measure: 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)
timeFrame: predose, up to 120 h after drug administration
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: predose, up to 120 h after drug administration
Secondary outcomes:
measure: %AUCtz-∞ (percentage of the AUCtz-∞ obtained by extrapolation from the last quantifiable data point to infinity)
timeFrame: predose, up to 120 h after drug administration
measure: AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 [predose] to 24 h)
timeFrame: predose, up to 120 h after drug administration
measure: tmax (time from dosing to the maximum concentration of the analyte in plasma)
timeFrame: predose, up to 120 h after drug administration
measure: λz (terminal rate constant of the analyte in plasma)
timeFrame: predose, up to 120 h after drug administration
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: predose, up to 120 h days after drug administration
measure: MRTpo (mean residence time of the analyte in the body after oral administration)
timeFrame: predose, up to 120 h after drug administration
measure: CL/F (apparent clearance of the analyte in plasma after extravascular administration)
timeFrame: predose, up to 120 h after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
timeFrame: predose, up to 120 h after drug administration
measure: Number of patients with abnormal findings in physical examination
timeFrame: Screening, up to 20 days after drug administration
measure: Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate)
timeFrame: Screening, up to 20 days after drug administration
measure: Number of patients with abnormal changes in laboratory parameters
timeFrame: Screening, up to 20 days after drug administration
measure: Number of patients with adverse events
timeFrame: up to 41 days
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: up to 20 days after drug administration
measure: Number of patients with abnormal changes in 12-lead electrocardiogram (ECG)
timeFrame: Screening, up to 20 days after drug administration
Other outcomes:
Locations:
Study officials:
References: