Safety, Tolerability and Pharmacokinetics of BIBW 2948 BS in Healthy Male Volunteers

A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Study to Evaluate Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses BIBW 2948 BS (0.75 to 150 mg Inhalation Powder, Hard Capsule for HandiHaler®) in Healthy Male Volunteers

Study to investigate safety, tolerability, and pharmacokinetics of BIBW 2948 BS

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BIBW 2948 BS for oral inhalation

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males based on a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests:

  • No finding deviating from normal and of clinical relevance
  • No evidence of a clinically relevant concomitant disease
• Aged between ≥21 and ≤50 years
• BMI (Body Mass Index) between ≥18.5 and ≤30 kg/m2
• Provision of written informed consent signed and dated prior to admission to the study in accordance with good clinical practice (GCP) and local legislation

Exclusion Criteria:

• Any finding during the medical examination (including BP, PR and 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
• 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 allergy to the drug or its excipients)
• Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (more than 60 g/day)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one week prior to administration or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of study centre

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: BIBW 2948 BS in single rising doses	Drug: BIBW 2948 BS for oral inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in vital signs (blood pressure, pulse rate, respiratory rate, orthostasis test, oral body temperature)		Up to 8 days after start of treatment
Changes from baseline in clinical laboratory tests		Up to 8 days after start of treatment
Changes from baseline in 12-lead electrocardiogram (ECG)		Up to 8 days after start of treatment
Number of patients with adverse events		Up to day 29
Changes from baseline in airway resistance (Raw)	measured via plethysmography	Pre-dose, up to 24 hours after start of treatment
Assessment of tolerability by investigator, a 4-point scale		Up to 8 days after start of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve of the analytes in plasma at different time points (AUCt1-t2)	Pre-dose, up to 48 hours after start of treatment
Maximum concentration of BIBW 3056 ZW in plasma (Cmax)	Pre-dose, up to 48 hours after start of treatment
Time from dosing to maximum concentration of the analytes in plasma (tmax)	Pre-dose, up to 48 hours after start of treatment
Amount of BIBW 3056 ZW eliminated in urine at different time points (Aet1-t2)	Pre-dose, up to 48 hours after start of treatment
Fraction of BIBW 3065 ZW eliminated in urine at different time points (fet1-t2)	Pre-dose, up to 48 hours after start of treatment
Renal clearance of BIBW 3056 ZW from 0 to 24 hours (CLR,0-24)	Pre-dose, up to 48 hours after start of treatment
Terminal rate constant of BIBW 3056 ZW in plasma (λz)	Pre-dose, up to 48 hours after start of treatment
Terminal half life of BIBW 3056 ZW in plasma (t½)	Pre-dose, up to 48 hours after start of treatment
Mean residence time of BIBW 3056 ZW in the body after inhalation (MRTih)	Pre-dose, up to 48 hours after start of treatment
Apparent clearance of BIBW 3056 ZW in the plasma after extravascular administration (CL/F)	Pre-dose, up to 48 hours after start of treatment
Apparent volume of distribution of BIBW 3056 ZW during the terminal phase λz following an extravascular dose (Vz/F)	Pre-dose, up to 48 hours after start of treatment
The percentage of the AUC 0-∞ that is obtained by extrapolation (%AUCtz-∞)	Pre-dose, up to 48 hours after start of treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): July 1, 2005

Study Registration Dates

• First Submitted: August 12, 2014
• First Submitted That Met QC Criteria: August 12, 2014
• First Posted (Estimate): August 13, 2014

Study Record Updates

• Last Update Posted (Estimate): August 13, 2014
• Last Update Submitted That Met QC Criteria: August 12, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 1219.1