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Relative Bioavailability of Tiotropium and Salmeterol After Inhalation of a Fixed Combined Dose Compared to Monocomponents in Healthy Male Volunteers

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ClinicalTrials.gov Identifier: NCT02254174
Recruitment Status : Completed
First Posted : October 1, 2014
Last Update Posted : October 1, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

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


Condition or disease Intervention/treatment Phase
Healthy Drug: Tiotropium/Salmeterol Drug: Serevent® Diskus® Drug: Spiriva® Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : March 2006
Actual Primary Completion Date : July 2006

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tiotropium/Salmeterol Drug: Tiotropium/Salmeterol
Fixed dose combination of tiotropium 7.5 μg and salmeterol 25 μg inhalation powder, PE capsule via HandiHaler®

Active Comparator: Serevent® Diskus® Drug: Serevent® Diskus®
Active Comparator: Spiriva® Drug: Spiriva®
Active Comparator: Spiriva® and Serevent® Diskus® Drug: Serevent® Diskus®
Drug: Spiriva®



Primary Outcome Measures :
  1. 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 ]
  2. Cmax (maximum measured concentration of salmeterol in blood plasma) [ Time Frame: Up to 8 hours after drug administration ]
  3. Ae0-8 (urinary excretion of tiotropium over an 8 hour interval) [ Time Frame: Up to 8 hours after drug administration ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Cmax (maximum measured concentration of tiotropium in blood plasma) [ Time Frame: Up to 8 hours after drug administration ]
  4. 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 ]
  5. tmax (time from dosing to the maximum concentration of in plasma) [ Time Frame: Up to 8 hours after drug administration ]
  6. λz (terminal rate constant in plasma) [ Time Frame: Up to 8 hours after drug administration ]
  7. t½ (terminal half-life of in plasma) [ Time Frame: Up to 8 hours after drug administration ]
  8. MRTih (mean residence time in the body after inhalational administration) [ Time Frame: Up to 8 hours after drug administration ]
  9. CL/F (apparent clearance of in the plasma after extravascular administration) [ Time Frame: Up to 8 hours after drug administration ]
  10. Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) [ Time Frame: Up to 8 hours after drug administration ]
  11. 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 ]
  12. fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) [ Time Frame: up to 8 hours after inhalation ]
  13. 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 ]
  14. Number of participants with abnormal findings in physical examination [ Time Frame: up to 90 days after first drug administration ]
  15. Number of participants with clinically significant changes in vital signs [ Time Frame: up to 90 days after first drug administration ]
  16. Number of participants with abnormal findings in 12-lead ECG [ Time Frame: up to 90 days after first drug administration ]
  17. Number of participants with abnormal changes in clinical laboratory parameters [ Time Frame: up to 90 days after first drug administration ]
  18. Number of participants with adverse events [ Time Frame: up to 90 days after first drug administration ]
  19. Tolerability assessed by investigator on a 4-point scale [ Time Frame: up to 90 days after first drug administration ]


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Ages Eligible for Study:   21 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 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

  2. Age ≥21 and ≤50 years
  3. BMI ≥18.5 and <30 kg/m2 (Body Mass Index)
  4. 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:

  1. Any finding of the medical examination (including BP, PR, and ECG measurements) deviating from normal and of clinical relevance
  2. Evidence of a clinically relevant concomitant disease
  3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
  5. History of relevant orthostatic hypotension, fainting spells or blackouts
  6. Chronic or relevant acute infections
  7. History of relevant allergy/hypersensitivity (including allergy to the drug or its excipients) as judged clinically relevant by the investigator
  8. 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
  9. 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
  10. Participation in another trial with an investigational drug within 2 months prior to randomisation
  11. Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
  12. Inability to refrain from smoking on trial days as judged by the investigator
  13. Alcohol abuse (more than 40 g alcohol a day)
  14. Drug abuse
  15. Blood donation (more than 100 mL blood within 4 weeks prior to randomisation or during the trial)
  16. Excessive physical activities within 1 week prior to randomisation or during the trial
  17. Any laboratory value outside the reference range that is of clinical relevance
  18. 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:

  19. Asthma or history of pulmonary hyperreactivity
  20. Hyperthyrosis
  21. Allergic rhinitis in need of treatment
  22. Clinically relevant cardiac arrhythmia
  23. 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:

  24. Hypersensitivity to tiotropium and/or related drugs of this class

Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02254174     History of Changes
Other Study ID Numbers: 1184.11
First Posted: October 1, 2014    Key Record Dates
Last Update Posted: October 1, 2014
Last Verified: September 2014
Additional relevant MeSH terms:
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Respiratory Aspiration
Respiration Disorders
Respiratory Tract Diseases
Pathologic Processes
Tiotropium Bromide
Salmeterol Xinafoate
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents