Bioavailability of Tiotropium + Olodaterol Fixed-dose Combination (5 μg/ 5 μg) in Chinese COPD Patients
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Lung Diseases; Pulmonary Disease, Chronic Obstructive
Intervention: Tiotropium; Olodaterol
Intervention description: Fixed dose combination; Fixed dose combination
Intervention MeSH terms: Tiotropium Bromide; Olodaterol
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to assess the pharmacokinetics of tiotropium +
      olodaterol fixed-dose combination (FDC) (5 μg/ 5 μg) delivered by the RESPIMAT inhaler after
      single dose and at steady state in Chinese patients with COPD.

      The secondary objective is to assess the safety of tiotropium + olodaterol FDC (5 μg/ 5 μg)
      delivered by the RESPIMAT inhaler after 3 weeks once daily treatment in Chinese patients with
      COPD.
    

Eligibility criteria:

        Inclusion criteria:

          -  All patients must sign an informed consent consistent with International Conference on
             Harmonisation-Good Clinical Practice (ICH-GCP) guidelines and local legislations prior
             to any study-related procedures, which includes medication washout and restrictions.

          -  All patients must have a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and
             must meet the following spirometric criteria:

        Patients must have relatively stable airway obstruction with a post-bronchodilator Forced
        Expiratory Volume in one second (FEV1) >=30% of predicted normal and <80% of predicted
        normal (ECSC,; and a postbronchodilator FEV1/ Forced Vital Capacity (FVC)<70% at Visit 1

          -  Male or female patients, 40 years of age or older.

          -  Patients must be current or ex-smokers with a smoking history of more than 10 pack
             years.

        Patients who have never smoked cigarettes must be excluded.

          -  Patients must be able to

               -  perform technically acceptable pulmonary function tests,

               -  maintain medication worksheet records during the study period,

               -  perform all other assessments as required in the protocol.

          -  Patients must be able to inhale medication in a competent manner from the RESPIMAT
             inhaler and from a metered dose inhaler (MDI).

          -  Male or female patients. Women of childbearing potential* must be ready and able to
             use highly effective methods of birth control per ICH M3(R2) that result in a low
             failure rate of less than 1% per year when used consistently and correctly. A list of
             contraception methods meeting these criteria is provided in the patient information.

               -  Women of childbearing potential are defined as:

        Any female who has experienced menarche and does not meet the criteria for "women not of
        childbearing potential" as described below.

        Women not of childbearing potential are defined as:

        Women who are postmenopausal (12 months with no menses without an alternative medical
        cause) or who are permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral
        oophorectomy or bilateral salpingectomy).

        Exclusion criteria:

          -  Patients with a significant disease other than Chronic Obstructive Pulmonary Disease
             (COPD); a significant disease is defined as a disease which, in the opinion of the
             investigator, may (i) put the patient at risk because of participation in the study,
             (ii) influence the results of the study, or (iii) cause concern regarding the
             patient's ability to participate in the study.

          -  Patients with a, in the opinion of the investigator, clinically relevant abnormal
             baseline haematology, blood chemistry, or urinalysis; all patients with an Serum
             Glutamic Oxaloacetic Transaminase (SGOT) >x 2 Upper Limit of Normal (ULN), Serum
             Glutamic Pyruvic Transaminase(SGPT) >x 2 ULN, bilirubin >x 2 ULN or creatinine >x 2
             ULN will be excluded regardless of clinical condition (a repeat laboratory evaluation
             will not be conducted in these patients).

          -  Patients with a history of asthma. For patients with allergic rhinitis or atopy,
             source documentation is required to verify that the patient does not have asthma. If a
             patient has a total blood eosinophil count ≥600/mm3, source documentation is required
             to verify that the increased eosinophil count is related to a non-asthmatic condition.

        Patients with any of the following conditions:

          -  A diagnosis of thyrotoxicosis (due to the known class side effect profile of
             ß2-agonists).

          -  A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class
             side effect profile of ß2-agonists)

          -  A history of myocardial infarction within 1 year of screening visit (Visit 1).

          -  Unstable or life-threatening cardiac arrhythmia.

          -  Hospitalization for heart failure within the past year.

          -  Known active tuberculosis.

          -  A malignancy for which patient has undergone resection, radiation therapy or
             chemotherapy within last five years (patients with treated basal cell carcinoma are
             allowed).

          -  A history of life-threatening pulmonary obstruction.

          -  A history of cystic fibrosis.

          -  Clinically evident bronchiectasis.

          -  A history of significant alcohol or drug abuse.

          -  Patients who have undergone thoracotomy with pulmonary resection (patients with a
             history of thoracotomy for other reasons should be evaluated as per exclusion
             criterion No. 1).

          -  Patients being treated with oral or patch β-adrenergics.

          -  Patients being treated with oral corticosteroid medication at unstable doses (i.e.,
             less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg
             of prednisone per day or 20 mg every other day.

          -  Patients who regularly use daytime oxygen therapy for more than one hour per day and
             in the investigator's opinion will be unable to abstain from the use of oxygen therapy
             during clinic visits.

          -  Patients who have completed a pulmonary rehabilitation program in the six weeks prior
             to the screening visit (Visit 1) or patients who are currently in a pulmonary
             rehabilitation program.

          -  Patients who have taken an investigational drug within one month or six half lives or
             within the wash out period (whichever is greater) prior to screening visit (Visit 1).

          -  Patients with known hypersensitivity to β-adrenergics and/or anticholinergic drugs,
             benzalkonium chloride (BAC), disodium edentate (EDTA) or any other component of the
             RESPIMAT inhalation solution.

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial

          -  Women of childbearing potential not using two highly effective methods of birth
             control*.

        Female patients will be considered to be of childbearing potential unless surgically
        sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two
        years.

        * as per ICH M3: a highly effective method of birth control is defined as those which
        result in a low failure rate (i.e., less than 1% per year) when used consistently and
        correctly.

          -  Patients who have previously been allocated in this study or are currently
             participating in another study.

          -  Patients who are unable to comply with pulmonary medication restrictions prior to
             allocation.