Back to resultsRelative Bioavailability of Tiotropium and Salmeterol After Inhalation of a Fixed Combined Dose Compared to Monocomponents in Healthy Male Volunteers
Primary Purpose
Healthy
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Tiotropium/Salmeterol
Serevent® Diskus®
Spiriva®
Sponsored by
About this trial
This is an interventional treatment trial for Healthy
Eligibility Criteria
Inclusion Criteria:
Healthy male based upon a complete medical history, including the physical examination, regarding vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG (electrocardiogram) 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 ≤50 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 GCP (Good Clinical Practice) 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 randomisation
- 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 enrolment in the study or during the study
- 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 this class
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Active Comparator
Active Comparator
Arm Label
Tiotropium/Salmeterol
Serevent® Diskus®
Spiriva®
Spiriva® and Serevent® Diskus®
Arm Description
Outcomes
Primary Outcome Measures
AUC0-∞ (area under the concentration-time curve of salmeterol in blood plasma over the time interval from 0 extrapolated to infinity);
Cmax (maximum measured concentration of salmeterol in blood plasma)
Ae0-8 (urinary excretion of tiotropium over an 8 hour interval)
Secondary Outcome Measures
AUC0-tz (area under the concentration-time curve in plasma over the time interval from 0 to the time of the last quantifiable data point)
AUC0-∞ (area under the concentration-time curve of tiotropium in blood plasma over the time interval from 0 extrapolated to infinity)
Cmax (maximum measured concentration of tiotropium in blood plasma)
AUCt1-t2 (area under the concentration time curve in plasma over the time interval t1 to t2)
tmax (time from dosing to the maximum concentration of in plasma)
λz (terminal rate constant in plasma)
t½ (terminal half-life of in plasma)
MRTih (mean residence time in the body after inhalational administration)
CL/F (apparent clearance of in the plasma after extravascular administration)
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2
fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)
CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)
Number of participants with abnormal findings in physical examination
Number of participants with clinically significant changes in vital signs
Number of participants with abnormal findings in 12-lead ECG
Number of participants with abnormal changes in clinical laboratory parameters
Number of participants with adverse events
Tolerability assessed by investigator on a 4-point scale
Full Information
NCT ID
NCT02254174
First Posted
September 29, 2014
Last Updated
September 30, 2014
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT02254174
Brief Title
Relative Bioavailability of Tiotropium and Salmeterol After Inhalation of a Fixed Combined Dose Compared to Monocomponents in Healthy Male Volunteers
Official Title
A Randomised, Open-label Four-way Crossover Study to Evaluate Relative Bioavailability of Tiotropium and Salmeterol After Inhalation of a Fixed Combined Single Dose (7.5 μg Tiotropium, 25 μg Salmeterol, Inhalation Powder, Hard Capsule, HandiHaler®2), a Free Combined Single Dose of 18 μg Tiotropium [Spiriva® HandiHaler®] and 50 μg Salmeterol [Serevent® Diskus®], a Single Dose of 50μg Salmeterol (Serevent® Diskus®) and a Single Dose of 18 μg Tiotropium (Spiriva® HandiHaler®) in Healthy Male Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
July 2006 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
Assessment of the relative bioavailability of a fixed dose combination of tiotropium and salmeterol compared to a free dose combination of the marketed products of tiotropium and salmeterol (Spiriva® and Serevent® Diskus®).
Assessment of the relative bioavailability of a fixed dose combination of tiotropium and salmeterol compared to tiotropium and salmeterol administered as individual mono substances from the marketed products.
Assessment of safety and tolerability of the fixed combination of tiotropium and salmeterol in a PE (Polyethylene) capsule administered via the HandiHaler® 2
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tiotropium/Salmeterol
Arm Type
Experimental
Arm Title
Serevent® Diskus®
Arm Type
Active Comparator
Arm Title
Spiriva®
Arm Type
Active Comparator
Arm Title
Spiriva® and Serevent® Diskus®
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Tiotropium/Salmeterol
Intervention Description
Fixed dose combination of tiotropium 7.5 μg and salmeterol 25 μg inhalation powder, PE capsule via HandiHaler®
Intervention Type
Drug
Intervention Name(s)
Serevent® Diskus®
Intervention Type
Drug
Intervention Name(s)
Spiriva®
Primary Outcome Measure Information:
Title
AUC0-∞ (area under the concentration-time curve of salmeterol in blood plasma over the time interval from 0 extrapolated to infinity);
Time Frame
Up to 8 hours after drug administration
Title
Cmax (maximum measured concentration of salmeterol in blood plasma)
Time Frame
Up to 8 hours after drug administration
Title
Ae0-8 (urinary excretion of tiotropium over an 8 hour interval)
Time Frame
Up to 8 hours after drug administration
Secondary Outcome Measure Information:
Title
AUC0-tz (area under the concentration-time curve in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time Frame
Up to 8 hours after drug administration
Title
AUC0-∞ (area under the concentration-time curve of tiotropium in blood plasma over the time interval from 0 extrapolated to infinity)
Time Frame
Up to 8 hours after drug administration
Title
Cmax (maximum measured concentration of tiotropium in blood plasma)
Time Frame
Up to 8 hours after drug administration
Title
AUCt1-t2 (area under the concentration time curve in plasma over the time interval t1 to t2)
Time Frame
up to 8 hours after inhalation
Title
tmax (time from dosing to the maximum concentration of in plasma)
Time Frame
Up to 8 hours after drug administration
Title
λz (terminal rate constant in plasma)
Time Frame
Up to 8 hours after drug administration
Title
t½ (terminal half-life of in plasma)
Time Frame
Up to 8 hours after drug administration
Title
MRTih (mean residence time in the body after inhalational administration)
Time Frame
Up to 8 hours after drug administration
Title
CL/F (apparent clearance of in the plasma after extravascular administration)
Time Frame
Up to 8 hours after drug administration
Title
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time Frame
Up to 8 hours after drug administration
Title
Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2
Time Frame
up to 8 hours after inhalation
Title
fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)
Time Frame
up to 8 hours after inhalation
Title
CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)
Time Frame
up to 8 hours after inhalation
Title
Number of participants with abnormal findings in physical examination
Time Frame
up to 90 days after first drug administration
Title
Number of participants with clinically significant changes in vital signs
Time Frame
up to 90 days after first drug administration
Title
Number of participants with abnormal findings in 12-lead ECG
Time Frame
up to 90 days after first drug administration
Title
Number of participants with abnormal changes in clinical laboratory parameters
Time Frame
up to 90 days after first drug administration
Title
Number of participants with adverse events
Time Frame
up to 90 days after first drug administration
Title
Tolerability assessed by investigator on a 4-point scale
Time Frame
up to 90 days after first drug administration
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy male based upon a complete medical history, including the physical examination, regarding vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG (electrocardiogram) 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 ≤50 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 GCP (Good Clinical Practice) 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 randomisation
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 enrolment in the study or during the study
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 this class
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
Learn more about this trial
Relative Bioavailability of Tiotropium and Salmeterol After Inhalation of a Fixed Combined Dose Compared to Monocomponents in Healthy Male Volunteers
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