A Study to Characterize Pharmacokinetics of Tiotropium + Olodaterol Fixed-dose Combination in Japanese Patients With COPD.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01703845
First received: October 8, 2012
Last updated: June 19, 2015
Last verified: June 2015
  Purpose

The primary objective of this study is to assess pharmacokinetics of tiotropium + olodaterol fixed-dose combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) delivered by the RESPIMAT inhaler after 3 weeks once daily treatment in Japanese patients with COPD.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium (high dose) + Olodaterol
Drug: Tiotropium (low dose) + Olodaterol
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised, Open-label, Parallel-group Trial to Assess Pharmacokinetics and Safety of Tiotropium + Olodaterol Fixed-dose Combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) Delivered by the RESPIMAT Inhaler After 3 Weeks Once Daily Treatment in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Cmax,ss (Olodaterol) [ Time Frame: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21 ] [ Designated as safety issue: No ]

    Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • AUCt1-t2,ss (Olodaterol) [ Time Frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 ] [ Designated as safety issue: No ]

    Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • AUC0-tz,ss (Olodaterol) [ Time Frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 ] [ Designated as safety issue: No ]

    Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • Tmax,ss (Olodaterol) [ Time Frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21 ] [ Designated as safety issue: No ]

    Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • Aet1-t2,ss (Olodaterol) [ Time Frame: from 0 to 4 hours following drug administration on day 21 ] [ Designated as safety issue: No ]

    Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • fe t1-t2,ss (Olodaterol) [ Time Frame: from 0 to 4 hours following drug administration on day 21 ] [ Designated as safety issue: No ]

    Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • CLR,t1-t2,ss (Olodaterol) [ Time Frame: from 0 to 4 hours following drug administration on day 21 ] [ Designated as safety issue: No ]

    Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • Cmax,ss (Tiotropium) [ Time Frame: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21 ] [ Designated as safety issue: No ]

    Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • AUCt1-t2,ss (Tiotropium) [ Time Frame: 15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21 ] [ Designated as safety issue: No ]

    Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • AUC0-tz,ss (Tiotropium) [ Time Frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21 ] [ Designated as safety issue: No ]

    Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • Tmax,ss (Tiotropium) [ Time Frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21 ] [ Designated as safety issue: No ]

    Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • Aet1-t2,ss (Tiotropium) [ Time Frame: from 0 to 4 hours following drug administration on day 21 ] [ Designated as safety issue: No ]

    Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • fe t1-t2,ss (Tiotropium) [ Time Frame: from 0 to 4 hours following drug administration on day 21 ] [ Designated as safety issue: No ]

    Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.


  • CLR,t1-t2,ss (Tiotropium) [ Time Frame: from 0 to 4 hours following drug administration on day 21 ] [ Designated as safety issue: No ]

    Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).

    Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.

    Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).



Secondary Outcome Measures:
  • Number of Participants With Adverse Events (Including Assessment Based on Physical Examination) [ Time Frame: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose ] [ Designated as safety issue: No ]
    Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.

  • Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG [ Time Frame: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose ] [ Designated as safety issue: No ]

    Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events.

    There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG.



Enrollment: 32
Study Start Date: October 2012
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tiotropium + Olodaterol (high dose)
Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT
Drug: Tiotropium (high dose) + Olodaterol
Tiotropium + Olodaterol solution for inhalation
Experimental: Tiotropium + Olodaterol (low dose)
Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT
Drug: Tiotropium (low dose) + Olodaterol
Tiotropium + Olodaterol solution for inhalation

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Diagnosis of chronic obstructive pulmonary disease
  2. Relatively stable airway obstruction with post FEV1=<30% of predicted normal and< 80% predicted normal and post FEV1/FVC <70%
  3. Male or female Japanese patients, 40 years of age or older
  4. Smoking history of more than 10 pack years

Exclusion criteria:

  1. Significant disease other than COPD
  2. Clinically relevant abnormal lab values
  3. History of asthma
  4. Diagnosis of thyrotoxicosis
  5. Diagnosis of paroxysmal tachycardia
  6. A marked baseline prolongation of QT/QTc interval
  7. A history of additional risk factors for Torsade de Pointes (TdP)
  8. History of myocardial infarction within 1 year of screening visit
  9. Unstable or life-threatening cardiac arrhythmia
  10. Hospitalization for heart failure within the past year
  11. Known active tuberculosis
  12. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
  13. History of life-threatening pulmonary obstruction
  14. History of cystic fibrosis
  15. Clinically evident bronchiectasis
  16. History of significant alcohol or drug abuse
  17. Thoracotomy with pulmonary resection
  18. Oral ß-adrenergics
  19. Oral corticosteroid medication at unstable doses
  20. Regular use of daytime oxygen therapy for more than one hour per day
  21. Pulmonary rehabilitation program in the six weeks prior to the screening visit
  22. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
  23. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
  24. Pregnant or nursing women
  25. Women of childbearing potential not using a highly effective method of birth control
  26. Patients who have previously been randomized in this study or are currently participating in another study
  27. Patients who are unable to comply with pulmonary medication restrictions
  28. Patients with narrow-angle glaucoma or micturition disorder due to prostatic hyperplasia etc
  29. Patients being treated with medications that prolong the QT/QTc interval
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703845

Locations
Japan
1237.24.24001 Boehringer Ingelheim Investigational Site
Toshima-ku, Tokyo, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01703845     History of Changes
Other Study ID Numbers: 1237.24
Study First Received: October 8, 2012
Results First Received: June 19, 2015
Last Updated: June 19, 2015
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Lung Diseases, Obstructive
Pathologic Processes
Respiratory Tract Diseases
Tiotropium
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 03, 2015