Clinical Endpoint Bioequivalence Study of Test and Reference Inhalation Products in Patients With COPD With Device Robustness

Study Overview
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Brief Summary
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The purpose of this study is to show bioequivalence of test product to reference product based on baseline-adjusted forced expiratory volume in one second (FEV1).

Official Title
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A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Crossover, Multicenter Clinical Study to Assess the Efficacy and Safety of Once Daily Administration of Lupin Tiotropium Bromide Inhalation Powder Compared to SPIRIVA® HANDIHALER® and Placebo in Patients With COPD Including a 12-Week Open Label Extension to Assess Inhaler Robustness

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: Test Product (tiotropium bromide inhalation powder)
* Drug: Reference Product (Spiriva®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non-pregnant female subjects (40 years of age and older). Patients with diagnosis of COPD according to the GOLD guidelines. Post-bronchodilator FEV1 <80% of the predicted value at the screening visit. Post-bronchodilator FEV1/FVC ratio ≤0.70 at the screening visit. Current or former smokers (e.g., with history of = 10 pack-years). Written informed consent. Exclusion Criteria: Known respiratory disorder other than COPD including, but not limited to the following: alpha-1 antitrypsin deficiency, cystic fibrosis, significant asthma, active bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, pulmonary edema, or interstitial lung disease. History of allergy or hypersensitivity to anticholinergic/muscarinic receptor antagonist agents, beta-2 adrenergic agonists, lactose/milk proteins, or known hypersensitivity to any of the proposed ingredients or components of the delivery system. Hospitalization for COPD or pneumonia within 12 weeks prior to the screening visit. Treatment for COPD exacerbation within 12 weeks prior to the screening visit. Viral or bacterial upper or lower respiratory tract infection, sinusitis, sinus infection, rhinitis, pharyngitis, middle ear infection, urinary tract infection, or illness within 6 weeks prior to the screening visit. Abnormal and significant ECG finding prior to the screening, during the run-in and treatment periods.

Ages Eligible for Study
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Minimum Age: 40 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
Interventional Model Description: Double-blind, double-dummy, placebo controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Product (tiotropium bromide inhalation powder)<br>Once daily administration of test product (tiotropium bromide inhalation powder), 18 mcg for open-label extension (device robustness). | Drug: Test Product (tiotropium bromide inhalation powder)<br>* Double-Blind: Single dose of test product 18 mcg of test product Open-Label: once daily administration of test product (tiotropium bromide inhalation powder) 18 mcg administered by test dry powder inhaler.<br>|
| Active Comparator: Reference Product (Spiriva®)<br>Single dose of reference product (Spiriva®) 18 mcg | Drug: Reference Product (Spiriva®)<br>* Reference product (Spiriva®) 18 mcg.<br>|
| Placebo Comparator: Placebo<br>Single dose of placebo inhalation powder | Drug: Placebo<br>* Single dose of placebo inhalation powder administered by test and reference dry powder inhalers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Adjusted Mean Change in FEV1 AUC0-24h Post Dose | To show clinical bioequivalence in the efficacy of the test product as a single dose versus reference product based on the baseline adjusted mean change in forced expiratory volume in the first second (FEV1) area under the curve from time zero to 24 hours post dose (AUC0-24h) on day 1 zero to 24 hours post-dose (AUC0-24h). Baseline was defined as the average of the FEV1 values recorded at approximately 30 minutes and 15 minutes before dosing with study medication. | 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks | 
| Difference in Baseline Adjusted FEV1 AUC0-24h for Comparison of Lupin Tiotropium Bromide Inhalation Powder (Test) and Spiriva (Reference) to Placebo | This measure is to demonstrate that test product as a single dose and reference product are superior to placebo based on the baseline adjusted mean change in forced expiratory volume in the first second (FEV1) area under the curve from time zero to 24 hours post dose (AUC0-24h) on day 1 zero to 24 hours post-dose (AUC0-24h). Baseline was defined as the average of the FEV1 values recorded at approximately 30 minutes and 15 minutes before dosing with study medication. | 0-24 hours after dosing on Day 1 of visits 2-4 over a period of approximately 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD