Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses of BI 1744 CL in Fixed Dose Combination With Tiotropium Bromide in Healthy Male Volunteers

October 7, 2014 updated by: Boehringer Ingelheim

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses (2 μg/5 μg, 10 μg/5 μg, and 40 μg/10 μg) of BI 1744 CL in Fixed Dose Combination With Tiotropium Bromide for 14 Days in Healthy Male Volunteers (Double-blind, Randomised, Placebo Controlled [at Each Dose Level] Study)

To investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 1744 CL and Tiotropium Bromide when given as fixed dose combination

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Healthy male based upon a complete medical history, including physical examination, regarding vital signs (BP, PR), 12-lead ECG measurement, and clinical laboratory tests. There is no finding deviating from normal and of clinical relevance. There is no evidence of a clinically relevant concomitant disease
  • Age ≥21 and ≤45 years
  • BMI ≥18.5 and <30 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

Exclusion Criteria:

  • Any finding of the medical examination (including BP, PR, and ECG measurements) deviating from normal and of clinical relevance
  • 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) as judged clinically relevant by the investigator
  • Intake of drugs with a long half-life (>24 hours) within at least 1 month or less than 10 half-lives of the respective drug prior to randomization
  • 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 randomisation
  • Participation in another trial with an investigational drug within 2 months prior to randomisation
  • Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
  • Inability to refrain from smoking on trial days as judged by the investigator
  • Alcohol abuse (more than 40 g alcohol a day)
  • Drug abuse
  • Blood donation (more than 100 mL blood within 4 weeks prior to randomisation or during the trial)
  • Excessive physical activities within 1 week prior to randomisation or during the trial
  • Any laboratory value outside the reference range that is of clinical relevance
  • Inability to comply with dietary regimen of the study centre

The following exclusion criteria are specific for this study due to the known class side effect profile of ß2-mimetics:

  • Asthma or history of pulmonary hyperreactivity
  • Hyperthyrosis
  • Allergic rhinitis in need of treatment
  • Clinically relevant cardiac arrhythmia
  • Paroxysmal tachycardia (>100 beats per minute)

The following exclusion criteria are specific for this study due to the known class side effect profile of Tiotropium:

  • Hypersensitivity to tiotropium and/or related drugs of these classes
  • History of narrow-angle glaucoma
  • History of prostatic hyperplasia
  • History of bladder-neck obstruction

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo
Experimental: BI 1744 CL in combination with Tiotropium
Drug: Single rising doses of BI 1744 CL, solution for oral inhalation
Drug: Tiotropium, fixed dose, solution for oral inhalation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of subjects with clinically relevant findings in physical examination
Time Frame: Up to day 32
Up to day 32
Number of subjects with clinically relevant findings in vital signs
Time Frame: Up to day 32
blood pressure, pulse rate
Up to day 32
Number of subjects with clinically relevant findings in 12-lead ECG
Time Frame: Up to day 32
Up to day 32
Number of subjects with clinically relevant findings in laboratory tests
Time Frame: Up to day 32
Up to day 32
Number of subjects witch clinically relevant changes in additional safety laboratory test parameters
Time Frame: up to 318 hours after start of treatment
Systemic metabolic parameters: cyclic adenosine mono phosphate (cAMP) and potassium
up to 318 hours after start of treatment
Number of subjects with clinically relevant changes in airway resistance (Raw) measured by body plethysmography
Time Frame: Pre-dose, up to 408 hours after start of treatment
Pre-dose, up to 408 hours after start of treatment
Number of subjects with adverse events
Time Frame: Up to day 32
Up to day 32
Global assessment of tolerability by investigator on a 4-point scale
Time Frame: Up to day 32
Up to day 32

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Maximum concentration in plasma (Cmax)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Time from dosing to maximum concentration in plasma (tmax)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Area under the concentration-time curve in plasma (AUC)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Percentage of AUC 0-∞ that is obtained by extrapolation (%AUCtz-∞)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Terminal rate constant in plasma (λz)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Terminal half-life in plasma (t½)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Mean residence time in the body after inhalation (MRTih)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Apparent clearance after extravascular administration (CL/F)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Amount eliminated in urine from the time point t1 to t2 (Aet1-t2)
Time Frame: up to 336 hours after start of treatment
up to 336 hours after start of treatment
Fraction excreted in urine from time point t1 to t2 (fet1-t2)
Time Frame: up to 336 hours after start of treatment
up to 336 hours after start of treatment
Renal clearance from the time point t1 until the time point t2 (CLR,t1-t2)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Minimum measured concentration in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Predose concentration of the analytes in plasma at steady state immediately before administration of the next dose (Cpre,ss)
Time Frame: Pre-dose every 24 hours
Pre-dose every 24 hours
Time of last measurable concentration in plasma (tz)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Linearity index (LI)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Accumulation ratio based on Cmax (RA,Cmax)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment
Accumulation ratio based on AUCτ (RA,AUC)
Time Frame: up to 504 hours after start of treatment
up to 504 hours after start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2007

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 7, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 9, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 9, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1237.2

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