A Study on Whether Patients Prefer the Spiriva® Respimat® or the Spiriva® Handihaler® for Treating Their Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The objective of this study is to investigate the patient acceptability/preference of Respimat® compared with Handihaler® in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) to demonstrate the superiority of Respimat®.

Official Title
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A Randomized, Open-label, Two-way Crossover Study to Compare Patient Acceptability/Preference of Tiotropium Respimat® With Tiotropium Handihaler® in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium Respimat® (T1)
* Drug: Tiotropium Handihaler® (T2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have a diagnosis of COPD and must meet the following spirometric criteria at Visit 1 (Screening). Relatively stable, moderate to very severe airway obstruction with a post-bronchodilator FEV1 <80% of predicted normal and FEV1/FVC <70%. Spirometry should be done at baseline and approximately 1/2 hour following 4 inhalations of albuterol. Male = exp [-10.61669 + 2.27078 × ln (- in cm) + 0.06622 × ln (age in year) + Mspline] Female = exp [-9.69716 + 2.09385 × ln (- in cm) + 0.02006 × ln (age in year) + Mspline] Historical data from spirometry measurements within the past 6 either at the site or at the other hospital may be used. If the measurements are not performed at the trial site a referral letter and signed copies of the measurement printouts must be provided to the trial site for source data verification. In case several qualifying spirometry measurements are available, the most recent one should be referred to as long as it was not performed during an exacerbation. Patients may not be randomised to the study without the availability of spirometry data at the actual study site. Male or female, age: ≥40 years of age Patients must be current or ex-smokers with a smoking history of ≥ 10 pack years. (Patients who have never smoked cigarettes must be excluded). Signed and dated written informed consent in accordance with International Council on Harmonization (ICH) ICH-GCP and local legislation prior to admission to the trial Patients must be able to inhale medication from the Tiotropium Respimat® and Tiotropium HandiHaler® Patients must be able to perform all study related procedures, and must be able to maintain records (patient diary) during the study period as required by the protocol Exclusion Criteria: Had visual, cognitive, or motor impairment that, as judged by the investigator, did not allow the patient to independently read and complete the PASAPQ questionnaire Patients have had used both Respimat® and HandiHaler® (including generic HandiHaler®) within one year prior to screening. Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patients at risk because of participation in the study or may influence either the results of the study or the patient's ability to participate in the study. All patients with an Aspartate Transaminase (AST) (serum glutamic-oxaloacetic transaminase, SGOT) >80 IU/L, Alanine Aminotransferase (ALT) (Serum Glutamic-pyruvic Transaminase, SGPT) >80 IU/L, Bilirubin >2.0 mg/dL or Creatinine >2.0 mg/dL will be excluded regardless of the clinical condition. Repeat laboratory evaluation will not be conducted in these subjects. Patients with a recent history (i.e., one year or less) of myocardial infarction. Patients who have been hospitalized or being treated for heart failure within the past year. Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year. Patients with a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed). Known active tuberculosis. Patients with a history of asthma, cystic fibrosis, clinically not well-controlled bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease History of thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated. Patients with any respiratory tract infection or COPD exacerbation in the 6 weeks prior to the initial screening visit (Visit 1). Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction. Patients whose symptoms are controlled on treatment may be included. Patients with known narrow-angle glaucoma Use of systemic corticosteroid medication at unstable doses (i.e., less than six weeks on stable dose) or at doses in excess of the equivalent of 10 milligrams (mg) prednisolone per day. Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral or injectable contraceptives, intrauterine devices (IUD) or diaphragm with spermicide, or Norplant®). Significant alcohol or drug abuse within the past 12 months Known hypersensitivity to anticholinergic drugs, lactose, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA) or any other components of the HandiHaler® or Respimat® inhalation solution delivery system. Patients currently in any pulmonary rehabilitation program or scheduled to participate in any such program during the study period. Previous participation in this study. (The patient cannot re-enroll into this study.) Patients who are currently participating in another interventional study.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (T1): 5μg tiotropium Respimat®, then (T2): 18μg tiotropium Handihaler®<br>From Day 1 of Period 1 participants received Test treatment (T1): tiotropium Respimat® (Spiriva® Respimat®) 5 microgram (μg) once daily for a duration of 4 weeks, given as 2.5μg per puff, two puffs (2.5μg per puff) inhalation solution of tiotropium, orally via Respimat®. From Day 1 of Period 2 participants received comparator treatment(T2): tiotropium Handihaler® (Spiriva®) 18μg once daily for a duration of 4 weeks, inhalation powder tiotropium with 1 Handihaler® device. | Drug: Tiotropium Respimat® (T1)<br>* inhalation solution<br>Drug: Tiotropium Handihaler® (T2)<br>* Inhalation Powder<br>|
| Experimental: (T2): 18μg tiotropium Handihaler®, then (T1): 5μg tiotropium Respimat®<br>From Day 1 of Period 1 participants received comparator treatment (T2): tiotropium Handihaler® (Spiriva®) 18 microgram (μg) once daily for a duration of 4 weeks, inhalation powder tiotropium with 1 Handihaler® device. From Day 1 of Period 2 participants received Test treatment (T1): tiotropium Respimat® (Spiriva® Respimat®) 5 microgram (μg) once daily for a duration of 4 weeks, given as 2.5μg per puff, two puffs (2.5μg per puff) inhalation solution of tiotropium, orally via Respimat®. | Drug: Tiotropium Respimat® (T1)<br>* inhalation solution<br>Drug: Tiotropium Handihaler® (T2)<br>* Inhalation Powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance Domain of the Patient Satisfaction and Preference Questionnaire (PASAPQ) After 4 Weeks of Treatment | The score on the performance domain of the Patient satisfaction and preference questionnaire (PASAPQ) after 4 weeks of treatment is reported. The performance domain score is the sum of 7 questions (Q) within the domain (Q1, Q2, Q3, Q4, Q5, Q10 and Q11), the range for each question went from 1 to 7 the higher the better. The score was then transformed to a 0 (least) to 100 (most) point scale following ((Q1+Q2+Q3+Q4+Q5+Q10+Q11)/49)*100, the higher the better performance. The performance domain of PASAPQ) was analysed using Mixed-effects Model for Repeated Measures (MMRM), with treatment and period as fixed effects, and patient as a random effect. Compound symmetry was used as a covariance structure for within-patient variation. | After 4 weeks of treatment (at week 4 and week 8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PASAPQ Total Score After 4 Weeks of Treatment | The total score on the Patient satisfaction and preference questionnaire (PASAPQ) after 4 weeks of treatment is reported. The Total score is the sum of 13 questions (Q1-Q13) and then transformed to a 0 (least) to 100 (most) point scale. This continuous secondary endpoint was analyzed using a similar MMRM model as for the primary endpoint. | After 4 weeks of treatment (at week 4 and week 8) | 
| Percentage of Patients Indicating Preference at Week 8 | The percentage of patients indicating preference in the Patient satisfaction and preference questionnaire (PASAPQ) at week 8 is reported. The questionnaire PASAPQ is a two part questionnaire, in Part II of the PASAPQ the stand-alone question 15 (Q15) was asked for a response to indicate the preference for the trial device, it had three possible answers: I prefer Respimat, I prefer Handihaler, No answer to this question  and no preference. Chi-squared test was used to analyze proportion of patients indicating preference in the Patient satisfaction and preference questionnaire (PASAPQ) at week 8. | At Week 8. | 
| Overall Satisfaction Question Score From PASAPQ After 4 Weeks of Treatment | The overall satisfaction question score in the Patient satisfaction and preference questionnaire (PASAPQ) at week 4 and 8 is reported (after 4 weeks of treatment). In Part I of the questionnaire PASAPQ: the Question 14 (Q14) asked for the overall satisfaction with the device used in the study. Q14 had Likert-type response options of 1 (very dissatisfied) to 7 (very satisfied) and was then transformed to a 0 (least) to 100 (most) point scale (if a patient scored x, the transfer to 0-100 scale was x/7*100). Mixed-effects Model for Repeated Measures (MMRM) was used to analyze the overall satisfaction question score, with treatment and period as fixed effects, and patient as a random effect. | At the end of 4 weeks of treatment | 
| Score on Willingness to Continue at Week 8 | The score on willingness to continue in the Patient satisfaction and preference questionnaire (PASAPQ) at week 8 is reported. The PASAPQ is a two part questionnaire, in Part I of the questionnaire PASAPQ the Question 16 (Q16) asked for a response between 0 and 100 with 0 indicating not willing to continue using the trial device and 100 indicating definitely willingness to continue. Mixed-effects Model for Repeated Measures (MMRM) was used to analyze the score on willingness to continue, with treatment and period as fixed effects, and patient as a random effect. | At Week 8. |