Clinical trial NCT05161156: Bioequivalence Study of Tiotropium Bromide Inhalation Powder
Official title: Multicentre,Randomized,Double-Blind,Double-Dummy,3period,6Seq,Crossover,Active&Placebo,SD PD Study to Evaluate Therapeutic Equivalence of Test Tiotropium Bromide Inh. Powder to Reference SPIRIVA® HANDIHALER in Subjects w/COPD*
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COPD
Lead sponsor: Phargentis SA
Sponsor class: INDUSTRY
First posted: 2021-12-17
Enrollment: 306
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, double-dummy, placebo controlled
Primary purpose: TREATMENT

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

Detailed description: Pharmadynamic study conducted in accordance requirements and recommendations per the US FDA's 2017 product specific "Draft Guidance on Tiotropium Bromide"

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Participants with history of liver or defined renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances.
2. 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
3. Participants with α1-antitrypsin deficiency as the underlying cause of COPD at screening.
4. Participants with history of paradoxical bronchospasm, narrow-angle glaucoma, prostatic hypertrophy, or bladder neck obstruction, which would contraindicate the use of an anticholinergic agent.
5. 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.
6. Participants with abnormal and clinically significant electrocardiogram (ECG) finding prior to the study screening and randomization as per investigator discretion.
7. Participants with use of oral/parenteral corticosteroids or antibiotics for COPD within 6 weeks or depot corticosteroids within 3 months prior to screening.
8. Participants with hospitalization for COPD or pneumonia within 12 weeks prior to study screening and randomization.
9. Participants with treatment for COPD exacerbation within 12 weeks prior to study screening and randomization.
10. 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.
11. Patients with sign and/or symptoms suggestive of COVID 19 infection at the time of screening.
12. Participants with lung volume reduction surgery within the previous 12 months of randomization.
13. Participants with chronic oxygen uses for \>12 hours/day.
14. 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.
15. 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.
16. Participants with history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
17. Participants with history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
18. Participant is unable to stop the medications at the defined times prior to screening
19. Participants with history of drug or alcohol abuse within 1 years before screening or positive test result(s) for alcohol or drugs of abuse at Screening.
20. Intended use of over the counter or prescription medication including herbal medications within 14 days prior to dosing.
21. Participants received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days or 5 half-lives prior to baseline, whichever is longer, or is currently enrolled in an investigational study.
22. Participants who are medically unable to withhold participant's salbutamol for the at least 4-hour period required prior to spirometry testing at each study visit.
23. Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 2 weeks after the last dose of study intervention.
24. Plans to father a child while enrolled in this study or within 2 weeks after the last dose of study intervention.
25. Participants that experiences a moderate or a severe COPD exacerbation or pneumonia during the run-in period will be excluded.
26. Participants requires nocturnal oxygen or continuous supplemental oxygen therapy.
27. Participant that requires a change in COPD medication from rescue medication or participants required rescue medications more than acceptable frequency during the screening or run-in period will be excluded.
28. Employee of the investigator or study site
29. Participants unable to perform maneuver (correct inhalation technique) according to study requirement despite device training
30. Participants unable to perform acceptable or repeatable spirometry or comply with other study procedures

Primary outcomes:
measure: Primary PD parameter - Adjusted area under the serial spirometry FEV1-time curve
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Anderson
country: United States
facility: Investigational Site 203
state: South Carolina
city: Gaffney
country: United States
facility: Investigational Site 204
state: South Carolina
city: Union
country: United States
facility: Investigational Site 205
state: South Carolina
city: Ahmedabad
country: India
facility: Investigational Site 119
state: Gujarat
city: Ahmedabad
country: India
facility: Investigational Site 101
state: Gujarat
city: Gandhinagar
country: India
facility: Investigational Site 120
state: Gujarat
city: Sabarmati
country: India
facility: Investigational Site 108
state: Gujarat
city: Sūrat
country: India
facility: Investigational Site 114
state: Gujarat
city: Vadodara
country: India
facility: Investigational Site 102
state: Gujarat
city: Vadodara
country: India
facility: Investigational Site 107
state: Gujarat
city: Jammu
country: India
facility: Investigational Site 118
state: Kashmir
city: Nagpur
country: India
facility: Investigational Site 106
state: Maharashtra
city: Nagpur
country: India
facility: Investigational Site 105
state: Maharashtra
city: Nashik
country: India
facility: Investigational Site 121
state: Maharashtra
city: Nashik
country: India
facility: Investigational Site 112
state: Maharashtra
city: Pune
country: India
facility: Investigational Site 111
state: Maharashtra
city: Barbengo
country: Switzerland
facility: Phargentis SA (Central Contact)
Study officials:
References: