Bioequivalence Study of Tiotropium Bromide Inhalation Powder

NCT05161156 | Completed Phase 3 FDA Drug FDA Device

• 1 other identifier: C2A01096
• Study Type: interventional
• Target: 306
• Locations: 3 countries
• Sites: 17

Brief Summary

This study is to characterize the pharmacodynamic characteristics and to assess the therapeutic bioequivalence after single dose of Tiotropium Bromide Inhalation Powder-test relative to Tiotropium Bromide Inhalation Powder-reference in Adult Patients with Chronic Obstructive Pulmonary Disease (COPD) as primary objective

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• Primary PD parameter - Adjusted area under the serial spirometry FEV1-time curve

  Baseline-adjusted area under the serial spirometry FEV1-time curve calculated from time 0 to 24 hours (AUC0-24h) following treatment

  24 hours

Study Arms (3)

Treatment A: 18 mcg of Test Product (tiotropium bromide inhalation powder)

EXPERIMENTAL

2 inhalations of test product, followed by 2 inhalations of reference placebo product

Combination Product: Test Product (tiotropium bromide inhalation powder); Combination Product: Placebo

Treatment B: 18 mcg of Reference Product (Spiriva)

ACTIVE COMPARATOR

2 inhalations of reference product, followed by 2 inhalations of test placebo product

Combination Product: 18 mcg of Spiriva (Reference Product); Combination Product: Placebo

Treatment C: Zero-dose (Placebo)

PLACEBO COMPARATOR

2 inhalations of reference placebo powder, followed by 2 inhalations of test placebo product

Combination Product: Placebo

Interventions

Test Product (tiotropium bromide inhalation powder) COMBINATION_PRODUCT

A single dose of test product

Treatment A: 18 mcg of Test Product (tiotropium bromide inhalation powder)

18 mcg of Spiriva (Reference Product) COMBINATION_PRODUCT

A single dose of reference product (Spiriva)

Also known as: RLD, SPIRIVA HandiHaler

Treatment B: 18 mcg of Reference Product (Spiriva)

Placebo COMBINATION_PRODUCT

A single dose of placebo

Treatment A: 18 mcg of Test Product (tiotropium bromide inhalation powder); Treatment B: 18 mcg of Reference Product (Spiriva); Treatment C: Zero-dose (Placebo)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must sign an ICF and is willing to participate in the study
• Male or female participant must be of ≥ 40 years of age
• Be medically stable on the basis of physical examination, medical history, and vital signs, chest X-ray and 12-lead ECG performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and recorded
• Be medically stable on the basis of clinical laboratory tests performed at screening as defined.
• Participants with documented Diagnosis of COPD, as defined by American Thoracic Society (ATS) \[GOLD criteria\] at screening.
• Pre-bronchodilator FEV1 ≥ 35% and ≤ 80% of predicted at screening and visits 3-5 as defined.
• Demonstrate at screening, post-bronchodilator FEV1≤80% of predicted.
• Must demonstrate at screening, post-bronchodilator FEV1/FVC ratio ≤0.70
• Demonstrate ≥ 15 % reversibility of FEV1 within 45 minutes following 4 inhalations of bronchodilator inhalation aerosol (84 mcg).
• Must administer at least 70% doses of placebo during the run-in period.
• Current or former cigarette smokers with a history of cigarette smoking of ≥10 pack-years at Screening (visit 1)
• Not pregnant , breastfeeding, not a woman of childbearing potential (WOCBP) or WOCBP using an acceptable contraceptive
• Participants willing and able to adhere to the protocol lifestyle restrictions
• Participants able to understand and comply with the study procedures.

You may not qualify if:

• Participants with history of liver or defined renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances.
• Known respiratory disorder other than COPD, including but not limited to the following: active tuberculosis, lung cancer, alpha-1-antitrypsin deficiency, cystic fibrosis, significant asthma, active bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, pulmonary edema or interstitial lung disease
• Participants with α1-antitrypsin deficiency as the underlying cause of COPD at screening.
• Participants with history of paradoxical bronchospasm, narrow-angle glaucoma, prostatic hypertrophy, or bladder neck obstruction, which would contraindicate the use of an anticholinergic agent.
• Participants with history of allergy or hypersensitivity to anticholinergic/muscarinic receptor antagonist agent, beta-2 adrenergic agonists, lactose/milk proteins or specific intolerance to aerosolized tiotropium or ipratropium bromide-containing products or known hypersensitivity to any of the proposed ingredients or components of the delivery system.
• Participants with abnormal and clinically significant electrocardiogram (ECG) finding prior to the study screening and randomization as per investigator discretion.
• Participants with use of oral/parenteral corticosteroids or antibiotics for COPD within 6 weeks or depot corticosteroids within 3 months prior to screening.
• Participants with hospitalization for COPD or pneumonia within 12 weeks prior to study screening and randomization.
• Participants with treatment for COPD exacerbation within 12 weeks prior to study screening and randomization.
• Participants with acute (viral or bacterial) upper or lower respiratory tract infection, sinusitis, rhinitis, pharyngitis, urinary tract infection or illness within 6 weeks prior to screening.
• Patients with sign and/or symptoms suggestive of COVID 19 infection at the time of screening.
• Participants with lung volume reduction surgery within the previous 12 months of randomization.
• Participants with chronic oxygen uses for \>12 hours/day.
• Participants with evidence or history of other clinically significant disease or abnormal (such as congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infarction, stroke, glaucoma or cardiac dysrhythmia) condition for which participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments.
• Participants had major surgery, (e.g., requiring general anesthesia) within 8 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time of the study.

Sponsors & Collaborators

• Phargentis SA: lead

Study Sites (17)

Investigational Site 203

Anderson, South Carolina, 29621, United States

Location

Investigational Site 204

Gaffney, South Carolina, 29340, United States

Location

Investigational Site 205

Union, South Carolina, 29379, United States

Location

Investigational Site 119

Ahmedabad, Gujarat, 380006, India

Location

Investigational Site 101

Ahmedabad, Gujarat, 382345, India

Location

Investigational Site 120

Gandhinagar, Gujarat, 382421, India

Location

Investigational Site 108

Sābarmatī, Gujarat, 380005, India

Location

Investigational Site 114

Surat, Gujarat, 395006, India

Location

Investigational Site 102

Vadodara, Gujarat, 390012, India

Location

Investigational Site 107

Vadodara, Gujarat, 390022, India

Location

Investigational Site 118

Jammu, Jammu and Kashmir, 190001, India

Location

Investigational Site 106

Nagpur, Maharashtra, 440009, India

Location

Investigational Site 105

Nagpur, Maharashtra, 440015, India

Location

Investigational Site 121

Nashik, Maharashtra, 422002, India

Location

Investigational Site 112

Nashik, Maharashtra, 422101, India

Location

Investigational Site 111

Pune, Maharashtra, 411038, India

Location

Phargentis SA (Central Contact)

Barbengo, 6917, Switzerland

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, double-dummy, placebo controlled

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: December 17, 2021
• Study Start: March 24, 2022
• Primary Completion: November 29, 2022
• Study Completion: November 29, 2022
• Last Updated: April 10, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1); US (3); IN (13)