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Study to Investigate Safety and Tolerability of BI 1744 CL in Free Dose Combination With Tiotropium Bromide Both Administered by Respimat® in Healthy Male Volunteers

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ClinicalTrials.gov Identifier: NCT02259946
Recruitment Status : Completed
First Posted : October 9, 2014
Last Update Posted : October 9, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
Study to investigate safety and tolerability of single, inhaled doses (2.5 μg, 5 μg, 10 μg, 20 μg and 40 μg) of BI 1744 CL in free dose combination with tiotropium bromide 5 μg (for doses up to and including 20 μg BI 1744 CL) and 10 μg (for doses of 20 μg and 40 μg BI 1744 CL), both administered by Respimat® in healthy male volunteers. Also, to investigate the pharmacokinetics of BI 1744 BS and tiotropium bromide in such combinations, to explore their dose proportionality, and to explore the pharmacodynamic effects of the treatments on selected metabolic and respiratory parameters

Condition or disease Intervention/treatment Phase
Healthy Drug: BI 1744 CL Drug: Placebo Drug: Tiotropium bromide Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Study to Assess Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses (2.5 μg, 5 μg, 10 μg, 20 μg and 40 μg) of BI 1744 CL (Administered With the Respimat®) in Free Dose Combination With Tiotropium Bromide 5 μg ( for Doses up to and Including 20 μg BI 1744 CL), 10 μg (for Doses of 20 μg and 40 μg BI 1744 CL) (Administered With the Respimat®) in Healthy Male Volunteers
Study Start Date : April 2006
Actual Primary Completion Date : July 2006

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BI 1744 CL - single rising dose + Tiotropium
Single rising dose of BI 1744 CL (conjointly with Tiotropium bromide)
Drug: BI 1744 CL
Drug: Tiotropium bromide
Placebo Comparator: Placebo Drug: Placebo



Primary Outcome Measures :
  1. Number of participants with abnormal findings in physical examination [ Time Frame: up to 12 days after drug administration ]
  2. Number of participants with abnormal changes in laboratory parameters [ Time Frame: up to 12 days after drug administration ]
  3. Number of participants with clinically significant changes in vital signs [ Time Frame: up to 12 days after drug administration ]
    blood pressure (BP), pulse rate (PR), respiratory rate (RR)

  4. Number of participants with adverse events [ Time Frame: up to 12 days after drug administration ]
  5. Number of participants with clinically significant changes in 12-lead ECG [ Time Frame: up to 12 days after drug administration ]
    cardiac axis, heart rate, PQ interval, QRS interval, uncorrected QT interval, HR-corrected QT-interval according to Bazett and Fridericia

  6. Number of abnormal findings on oropharyngeal inspection [ Time Frame: up to 24 hours after drug administration ]
  7. Number of abnormal findings on pulmonary auscultation [ Time Frame: up to 24 hours after drug administration ]
  8. Assessment of tolerability by investigator on a 4-point scale [ Time Frame: 12 days after drug administration ]
  9. Change in Airway resistance (Raw) [ Time Frame: up to 24 hours after drug administration ]
    measured by whole-body plethysmography

  10. Change in specific conductance (sGaw) [ Time Frame: up to 24 hours after drug administration ]
    measured by whole-body plethysmography

  11. Change in Cyclic aminomonophosphate (cAMP) [ Time Frame: up to 6 hours after drug administration ]
  12. Change in potassium [ Time Frame: up to 6 hours after drug administration ]

Secondary Outcome Measures :
  1. Cmax (maximum measured concentration of BI 1744 BS and tiotropium in plasma) [ Time Frame: up to 96 hours after drug administration ]
  2. tmax (time from dosing to maximum measured concentration) [ Time Frame: up to 96 hours after drug administration ]
  3. AUC0-∞ (area under the concentration-time curve of BI 1744 BS and tiotropium in plasma over the time interval from 0 extrapolated to infinity) [ Time Frame: up to 96 hours after drug administration ]
  4. AUC0-tz (area under the concentration-time curve of the analyte salmeterol in plasma over the time interval from 0 to the time of the last quantifiable data point) [ Time Frame: up to 96 hours after drug administration ]
  5. %AUCtz-∞ (percentage of the extrapolated part of the total AUC0-∞) [ Time Frame: up to 96 hours after drug administration ]
  6. λz (terminal rate constant in plasma) [ Time Frame: up to 96 hours after drug administration ]
  7. t1/2 (terminal half-life of BI 1744 BS and tiotropium in plasma) [ Time Frame: up to 96 hours after drug administration ]
  8. MRTih (mean residence time of BI 1744 BS and tiotropium in the body after inhalation) [ Time Frame: up to 96 hours after drug administration ]
  9. CL/F (apparent clearance of BI 1744 BS and tiotropium in plasma after extravascular administration) [ Time Frame: up to 96 hours after drug administration ]
  10. Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) [ Time Frame: up to 96 hours after drug administration ]
  11. Aet1-t2 (amount of BI 1744 BS and tiotropium eliminated in urine from the time point t1 to time point t2) [ Time Frame: up to 96 hours after drug administration ]
  12. fet1-t2 (fraction of BI 1744 BS and tiotropium eliminated in urine from time point t1 to time point t2) [ Time Frame: up to 96 hours after drug administration ]
  13. CLR,t1-t2 (renal clearance of BI 1744 BS and tiotropium from the time point t1 until the time point t2) [ Time Frame: up to 96 hours after 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 measurement, and clinical laboratory tests. Absence of any clinically relevant abnormality. Absence of any 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 Good Clinical Practice (GCP) 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 randomization
  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 randomization
  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 (regularly more than 40 g alcohol per day for men)
  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 randomization 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

    Additionally, following exclusion criteria that are of particular relevance with regard to the known properties of BI 1744 CL as a ß-adrenoceptor agonist must be adhered to:

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

    Furthermore, the following exclusion criteria that are of particular relevance with regard to the known properties of tiotropium as an antimuscarinic anticholinergic agent must be adhered to:

  24. Hypersensitivity to tiotropium and/or related drugs of these classes
  25. History of narrow-angle glaucoma
  26. History of prostatic hyperplasia
  27. History of bladder-neck obstruction

Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02259946     History of Changes
Other Study ID Numbers: 1237.1
First Posted: October 9, 2014    Key Record Dates
Last Update Posted: October 9, 2014
Last Verified: October 2014
Additional relevant MeSH terms:
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Bromides
Tiotropium Bromide
Olodaterol
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
Anticonvulsants