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

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

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).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Test Product (tiotropium bromide inhalation powder); Drug: Reference Product (Spiriva®); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 377
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Andalusia, Alabama, United States, 36420
      • Investigational Research Center Site #1017
    • Jasper, Alabama, United States, 35501
      • Investigational Research Center Site #1003
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Investigational Research Center Site #1008
  • California
    • Los Angeles, California, United States, 90025
      • Investigational Research Center Site #1034
    • Riverside, California, United States, 92506
      • Investigational Research Center Site #1028
    • Westminster, California, United States, 92683
      • Investigational Research Center Site #1010
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Investigational Research Center Site #1016
  • Florida
    • Clearwater, Florida, United States, 33756
      • Investigational Research Center Site #1026
    • Clearwater, Florida, United States, 33765
      • Investigational Research Center Site #1019
    • Clearwater, Florida, United States, 33765
      • Investigational Research Center Site #1035
    • Orlando, Florida, United States, 32825
      • Investigational Research Center Site #1036
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Investigational Research Center Site #1001
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Investigational Research Center Site #1011
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Investigational Research Center Site #1029
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Investigational Research Center Site #1007
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Investigational Research Center Site #1032
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Investigational Research Center Site #1037
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Investigational Research Center Site #1018
    • Oklahoma City, Oklahoma, United States, 73103
      • Investigational Research Center Site #1009
    • Tulsa, Oklahoma, United States, 74136
      • Investigational Research Center Site #1033
  • Oregon
    • Medford, Oregon, United States, 97504
      • Investigational Research Center Site #1005
    • Portland, Oregon, United States, 97202
      • Investigational Research Center Site #1006
  • South Carolina
    • Easley, South Carolina, United States, 29640
      • Investigational Research Center Site #1015
    • Gaffney, South Carolina, United States, 29340
      • Investigational Research Center Site #1012
    • Rock Hill, South Carolina, United States, 29732
      • Investigational Research Center Site #1023
    • Seneca, South Carolina, United States, 29678
      • Investigational Research Center Site #1024
    • Spartanburg, South Carolina, United States, 29303
      • Investigational Research Center Site #1020
    • Spartanburg, South Carolina, United States, 29303
      • Investigational Research Center Site #1025
    • Union, South Carolina, United States, 29379
      • Investigational Research Center Site #1027
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Investigational Research Center Site #1004
  • Texas
    • El Paso, Texas, United States, 79903
      • Investigational Research Center Site #1013
    • McKinney, Texas, United States, 75069
      • Investigational Research Center Site #1002
    • New Braunfels, Texas, United States, 78130
      • Investigational Research Center Site #1030
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Investigational Research Center Site #1031

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Product (tiotropium bromide inhalation powder); 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); 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.
Active Comparator: Reference Product (Spiriva®); Single dose of reference product (Spiriva®) 18 mcg	Drug: Reference Product (Spiriva®); Reference product (Spiriva®) 18 mcg.
Placebo Comparator: Placebo; Single dose of placebo inhalation powder	Drug: Placebo; Single dose of placebo inhalation powder administered by test and reference dry powder inhalers.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lupin, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): January 31, 2018
• Study Completion (Actual): April 30, 2018

Study Registration Dates

• First Submitted: April 30, 2017
• First Submitted That Met QC Criteria: April 30, 2017
• First Posted (Actual): May 3, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides
• Other Study ID Numbers: TB-DPI-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No