CTRI/2022/01/039634 [Registered on: 21/01/2022] Trial Registered Prospectively
Last Modified On:
17/10/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
A clinical study to determine bioequivalence, safety and tolerability of drug called Tiotropium Bromide Inhalation Powder
Scientific Title of Study
A Multicentre, Randomized, Double Blind, Double-Dummy, Three-period, Six-Sequence, Crossover, Active and Placebo Controlled, Single Dose Pharmacodynamic Study to Evaluate Therapeutic Equivalence of Test Formulation Tiotropium Bromide Inhalation Powder to Reference Formulation SPIRIVA® HANDIHALER® (Tiotropium bromide inhalation powder) in participants with Chronic Obstructive Pulmonary Disease.
18 mcg capsule of Test inhaler (2 Inhalation) and Zero dose Reference Placebo inhaler (2 Inhalation) with device, OD preferably in the morning between 7:00 am to 11:00 am. Single dose in one
period.
Comparator Agent
Tiotropium Bromide Inhalation Powder
18 mcg capsule of Reference inhaler (2 Inhalation) and Zero dose Test Placebo inhaler (2 Inhalation) with device, OD preferably in the morning between 7:00 am to 11:00 am. Single dose in one
period.
Intervention
Treatment C: Zero-dose (Placebo) of Reference and Test
Zero dose capsule of Reference placebo inhaler (2 Inhalation) and Zero dose Test Placebo inhaler (2 Inhalation) with device, OD preferably in the morning between 7:00 am to 11:00 am. Single dose in one
period.
Inclusion Criteria
Age From
40.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Participant must sign an ICF indicating that he or she understands the purpose of, and procedures required for the study in this protocol and is willing to participate in the study.
2. Male or female participant must be of ≥ 40 years of age, at the time of signing the informed consent.
Participants who are 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 this determination must be recorded in the participants source documents and initialed by the investigator.
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. At visits 3-5, the average of the quality FEV1 measurements will be used to determine the baseline FEV1, and must be ≥ 35% and ≤ 80% of predicted normal value and may not vary by more than ± 20% from the qualifying screening visit FEV1 value.
Participant must demonstrate at screening, post-bronchodilator FEV1≤80% of predicted.
8. Participant must demonstrate at screening, post-bronchodilator FEV1/FVC ratio ≤0.70.
Participant demonstrate ≥ 15 % reversibility of FEV1 within 45 minutes following 4 inhalations of ipratropium bromide HFA inhalation aerosol (84 mcg) at Screening.
10. Participants must administer at least 70% doses of placebo during the run-in period.
Participants who are Current or former cigarette smokers with a history of cigarette smoking of ≥10 pack-years at Screening (visit 1) Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1
12. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
a. Is not a woman of childbearing potential (WOCBP) b. Is a WOCBP and using an acceptable contraceptive method as
described in Appendix 10.4 during the intervention period and at a
minimum 15 days until after the last dose of study intervention. The
investigator should evaluate the effectiveness of the contraceptive
method in relationship to the first dose of study intervention. c. A WOCBP must have a negative highly sensitive serum pregnancy
test at screening and negative urine pregnancy test prior to dosing of
period I.
Participants willing and able to adhere to the lifestyle restrictions specified in this protocol.
14. Participants able to understand and comply with the study procedures, in the opinion of the investigator.
ExclusionCriteria
Details
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Participants with history of liver or renal insufficiency (estimated creatinine clearance below 60 mL/min); 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, in the investigator’s opinion, 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 use of oral/parenteral corticosteroids or antibiotics for COPD within 6 weeks or depot corticosteroids within 3 months prior to screening.
7. Participants with hospitalization for COPD or pneumonia within 12 weeks prior to study screening and randomization.
8. Participants with treatment for COPD exacerbation within 12 weeks prior to study screening and randomization. 9. Participants with acute (viral or bacterial) upper or lower respiratory tract infection include sinusitis, rhinitis, pharyngitis, urinary tract infection or illness within 6 weeks prior to screening.
10. Patients with sign and/or symptoms suggestive of COVID 19 infection at the time of screening.
11. Participants with lung volume reduction surgery within the previous 12 months of randomization.
12. Participants with chronic oxygen uses for >12 hours/day.
13. 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, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
14. 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 the participant is expected to participate in the study.
15. 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.
16. Participants with history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening. 17. Participant is unable to stop the medications at the defined times prior to screening spirometry.
18. 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.
19. Intended use of over the counter or prescription medication including herbal medications within 14 days prior to dosing.
20. 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, before the signing the consent or is currently enrolled in an investigational study.
21. Participants who are medically unable to withhold their salbutamol for the at least 4-hour period required prior to spirometry testing at each study visit.
22. 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.
23. Plans to father a child while enrolled in this study or within 2 weeks after the last dose of study intervention. 24. Participants that experiences a moderate or a severe COPD exacerbation or pneumonia during the run-in period will be excluded. 25. Participants requires nocturnal oxygen or continuous supplemental oxygen therapy.
26. Participant that requires a change in COPD medication from rescue medication or participants required rescue medications more than acceptable frequency (two inhalations every 4 to 6 hours) during the screening or run-in period will be excluded.
27. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator. 28. Participants unable to perform maneuver (correct inhalation technique) according to study requirement despite of giving device training as per investigator discretion.
29. Participants unable to perform acceptable or repeatable spirometry or comply with other study procedures
Method of Generating Random Sequence
Other
Method of Concealment
Other
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
Following Pharmacodynamic parameters will be evaluated: Primary PD parameter: Baseline-adjusted area under the serial FEV1-time curve calculated from time 0 to 24 hours (AUC0-24h) following treatment.
Baseline FEV1 is defined as the average of at least two quality pre-dose FEV1 values.
24 Hours
Secondary Outcome
Outcome
TimePoints
Following Pharmacodynamic parameters will be
evaluated:
Secondary PD parameter: FEV1 peak (Time to peak response(Tmax))
24 Hours
Target Sample Size
Total Sample Size="300" Sample Size from India="225" Final Enrollment numbers achieved (Total)= "298" Final Enrollment numbers achieved (India)="296"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is A Multicentre,
Randomized, Double Blind, Double-Dummy, Three-period, Six-Sequence, Crossover,
Active and Placebo Controlled, Single Dose Pharmacodynamic Study, to Evaluate
Therapeutic Equivalence of Test Formulation Tiotropium Bromide Inhalation
Powder to Reference Formulation of Tiotropium bromide inhalation powder in
participants with Chronic Obstructive Pulmonary Disease. This study have 3
phase Screening period,
Placebo run-in period and Double blind treatment phase (single dose in each
period) At the randomization visit, participants who meet all of the
eligibility criteria will be randomised 1:1:1 to receive single dose (2
inhalations from the same capsule per device; a total of 4 inhalations from 2
devices) of test, reference or placebo during each period. After dosing at
specified time point’s spirometry will be done to assess the FEV1 during each
period. To characterize the
pharmacodynamic characteristics and to assess the therapeutic bioequivalence and Superiority after single dose of Tiotropium Bromide
Inhalation Powder-test and Tiotropium Bromide Inhalation Powder-reference over
placebo in Adult Patients with Chronic Obstructive Pulmonary Disease (COPD).