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Completed

NCT Number: NCT01703845

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

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.

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Key information

Conditions

Pulmonary Disease, Chronic Obstructive Chronic Disease Disease Attributes Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

1237.24.24001 Boehringer Ingelheim Investigational Site

Toshima-ku, Tokyo, Japan

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Significant disease other than COPD
  • Clinically relevant abnormal lab values
  • History of asthma
  • Diagnosis of thyrotoxicosis
  • Diagnosis of paroxysmal tachycardia
  • A marked baseline prolongation of QT/QTc interval
  • A history of additional risk factors for Torsade de Pointes (TdP)
  • History of myocardial infarction within 1 year of screening visit
  • Unstable or life-threatening cardiac arrhythmia
  • Hospitalization for heart failure within the past year
  • Known active tuberculosis
  • Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
  • History of life-threatening pulmonary obstruction
  • History of cystic fibrosis
  • Clinically evident bronchiectasis
  • History of significant alcohol or drug abuse
  • Thoracotomy with pulmonary resection
  • Oral ß-adrenergics
  • Oral corticosteroid medication at unstable doses
  • Regular use of daytime oxygen therapy for more than one hour per day
  • Pulmonary rehabilitation program in the six weeks prior to the screening visit
  • Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
  • Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
  • Pregnant or nursing women
  • Women of childbearing potential not using a highly effective method of birth control
  • Patients who have previously been randomized in this study or are currently participating in another study
  • Patients who are unable to comply with pulmonary medication restrictions
  • Patients with narrow-angle glaucoma or micturition disorder due to prostatic hyperplasia etc
  • Patients being treated with medications that prolong the QT/QTc interval

Treatment and study plan

Tiotropium (high dose) + Olodaterol

Drug

Tiotropium + Olodaterol solution for inhalation

Tiotropium (low dose) + Olodaterol

Drug

Tiotropium + Olodaterol solution for inhalation

Primary outcomes

  1. 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

    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.

  2. 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

    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.

  3. 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

    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.

  4. 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

    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.

  5. Aet1-t2,ss (Olodaterol)

    Time frame: from 0 to 4 hours following drug administration on day 21

    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.

  6. fe t1-t2,ss (Olodaterol)

    Time frame: from 0 to 4 hours following drug administration on day 21

    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.

  7. CLR,t1-t2,ss (Olodaterol)

    Time frame: from 0 to 4 hours following drug administration on day 21

    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.

  8. 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

    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.

  9. 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

    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.

  10. 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

    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.

  11. 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

    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.

  12. Aet1-t2,ss (Tiotropium)

    Time frame: from 0 to 4 hours following drug administration on day 21

    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.

  13. fe t1-t2,ss (Tiotropium)

    Time frame: from 0 to 4 hours following drug administration on day 21

    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.

  14. CLR,t1-t2,ss (Tiotropium)

    Time frame: from 0 to 4 hours following drug administration on day 21

    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 outcomes

  1. 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

    Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.

  2. 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

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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)

Important dates

Study start
2012
Primary completion
2013
Study completion
2013
First posted
Oct 11, 2012
Registry last updated
Jul 15, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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