CTRI/2023/01/049303 [Registered on: 31/01/2023] Trial Registered Prospectively
Last Modified On:
13/02/2024
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 in patients with Chronic Obstructive Pulmonary Disease
Scientific Title of Study
A Multicenter, Randomized, Placebo-Controlled, Crossover, Single Dose Study to Demonstrate Clinical Pharmacodynamic Bioequivalence of Tiotropium 18 mcg Inhalation Powder, Hard Capsule with Spiriva Handihaler 18 mcg Inhalation Powder, Hard Capsule in Patients with Chronic Obstructive Pulmonary Disease
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
17-QC-005 (2019-TIOT-0200-PD-01) V 5.0, 23 Dec 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dharmesh Domadia
Designation
Vice President-Global Clinical Operation
Affiliation
cliantha research limited
Address
Department of Clinical trials, Room no 01, 2nd floor, 6, Arista@Eight Corporate House, Near Satyam House, Behind RajpathClub,Bodakdev, Ahmedabad- 380054, Gujarat, India.
Ahmadabad GUJARAT 380054 India
Phone
079-66219555
Fax
Email
ddomadia@cliantha.com
Details of Contact Person Scientific Query
Name
Dr Nil Desai
Designation
Medical Monitor
Affiliation
cliantha research limited
Address
6, Arista@Eight Corporate House, Near Satyam House, Behind RajpathClub,Bodakdev, Ahmedabad- 380054, Gujarat, India
Ahmadabad GUJARAT 380054 India
Phone
9879732959
Fax
Email
nhdesai@cliantha.com
Details of Contact Person Public Query
Name
Mr Devesh Verma
Designation
Associate Director-I
Affiliation
cliantha research limited
Address
6, Arista@Eight Corporate House, Near Satyam House, Behind RajpathClub,Bodakdev, Ahmedabad- 380054, Gujarat, India
Ahmadabad GUJARAT 380054 India
Phone
9712908404
Fax
Email
dverma@cliantha.com
Source of Monetary or Material Support
Laboratorios Liconsa S.A.
Primary Sponsor
Name
Laboratorios Liconsa S.A.
Address
Avda. Miralcampo, 7 19200 Azuqueca de Henares, Guadalajara, Spain
Besides Nilamkunj Society, Nr. Gokulnathji Haveli, Mira Cinema Cross Road, Bhairavnath, Shah Alam Rd, Maninagar, Ahmedabad- 380028, Gujarat, India Ahmadabad GUJARAT
9428605404
kunjan7290@gmail.com
Dr Arti Shah
Dhawal Multispeciality Hospital
39/40 Sahajanand Society, Harni-Warasiya Ring Road, Vadodara, Gujarat-390022 Vadodara GUJARAT
9925047880
artidhawal76@gmail.com
Dr Maulesh Tailor
Divine Multispeciality Hospital
2nd & 3rd Floor, Shikshapatri Sky Court, Near Swagat Flamingo, Sargasan, Gandhinagar-382421, Gujarat India Gandhinagar GUJARAT
9979867922
drmauleshtailor@yahoo.com
Dr Mahesh Vaghani
Global Hospital
Global Hospital, 4th Floor, Global Point, Nr Navjivan Resturant sarthana jakatnaka, surat-395006, Gujarat, India Surat GUJARAT
9825433984
globalhospitalcr@gmail.com
Dr Naveed Shah
Govt. Chest disease hospital
Department of Pulmonary Medicine, Govt. medical College, Buchwara Dalgate, Srinagar - 190001, J&K, India, Srinagar JAMMU & KASHMIR
9419016438
naveednazirshah@yahoo.com
Dr Rahul Pandya
Hatkesh Healthcare Foundation
2nd Floor, Hatkesh Healthcare Foundation, Nr. Bhutnath Temple, College Road, Junagadh 362001, Gujarat, India Junagadh GUJARAT
9558613300
Droandyarahul@gmail.com
Dr Jinesh Shah
Hope Medicare Center
Hope Medicare Center, 205/206, saransh-2, Asharfi kulfi outlet, channawad police chowki to bhudarpur road, Ambawadi, Ahmedabad -380006, Gujarat, India Ahmadabad GUJARAT
9879531832
drjinesh17@gmail.com
Dr Manishkumar Jain
Maharaja Agrasen Multispeciality Hospital
Room No. 9, Basement, Clinical Research department, Maharaja Agrasen superspeciality
Hospital, Central Spine, Agrasen Aspatal marg, Sector -7, Vidyadhar Nagar, Jaipur, Rajasthan 302039, India Jaipur RAJASTHAN
9414414834
doctormanisgjain2@gmail.com
Dr Snehal Kothari
Shraddha Hospital
Vaibhav Complex, Near Multispeciality Hospital, Kalol, Gandhinagar, Gujarat 382721, India Gandhinagar GUJARAT
9825093242
snehalbk@rediffmail.com
Dr Balki Akash Lataru
Shree Hospital & Critical Care Centre
799, Om Nagar, opp. Tajshree Building sakkardara square nagpur-440009, Maharashtra, India Nagpur MAHARASHTRA
1. Capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the Investigator, capable of giving written informed consent and being compliant with all study requirements (visits, study procedures such as pulmonary function tests, record-keeping, etc.).
2. Male or non-pregnant female patients between 40 to 75 years of age at Screening Visit (Visit 1) diagnosed with COPD who have signed informed consent prior to initiation of any study-related procedure.
3. General good health (except the COPD diagnosis) and free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the study as per the discretion of the Investigator.
4. An established physician diagnosis of COPD as defined by the American Thoracic Society
5. At first (Visit 1) or second (Visit 2) Screening Visit, post-bronchodilator FEV1≤80% and ≥40% of predicted normal values as per Global Lung Function Initiative (GLI-2012) after 4 puffs of albuterol used as per GOLD 2022. Additionally, post-bronchodilator FEV1/FVC ratio ≤0.70.
6. Pre dose FEV1 values at Visits 4 and 5 within ± 20% of the Visit 3 FEV1.
7. Able to perform spirometry according to the defined acceptability and reproducibility criteria at the Screening Visit (Visit 1 or 2).
8. Current COPD Therapy: Patients must be on stable regimens of one of the following for at least 8 weeks prior to screening (Visit 1):
• Long-acting beta-agonist (LABA)
• Long-acting muscarinic antagonist (LAMA)
• LAMA+LABA
• Inhaled corticosteroids + LABA
• Inhaled corticosteroids + LAMA
• Short-acting beta-agonist (SABA)
9. All patients must be able to replace their current short-acting bronchodilators with study-provided albuterol inhalation aerosol provided at the Screening Visit (Visit 1) for use as needed for the duration of the study.
10. Patients must be able to discontinue their COPD maintenance medications during the run-in and treatment periods.
11. Patients must be able to withhold their short-acting β2-agonists for at least 6 hours prior to spirometry on each clinic visit at the discretion of the investigator.
12. Current or ex-smokers with ≥10 pack-year smoking history
13. Female patients may be of non-childbearing potential (postmenopausal, i.e., amenorrheal for >2 consecutive years, or naturally postmenopausal [no menses] for ≥1 year; surgically sterile [tubal ligation, bilateral oophorectomy, or hysterectomy], congenital sterility, or diagnosed as infertile and not undergoing treatment to reverse infertility) or if of childbearing potential committed to the consistent and correct use of an acceptable method of birth control and demonstrate a negative pregnancy test at the Screening Visit (Visit 1) and during the study.
14. Male subjects, who are sexually active, committed to the consistent and correct use of an acceptable method of birth control for the duration of the study, and/or exclusively have same-sex partners.
15. No occurrence of an upper or lower respiratory tract infection during the run-in period.
16. No COPD exacerbation, defined as any worsening of COPD requiring an emergency department visit or hospitalization, or requiring excessive use of the albuterol rescue medication (more than 3 puffs per day increase from the average daily usage) during the run-in and/or treatment period at the discretion of the Investigator, or the use of antibiotics and/or corticosteroids during the run-in period and/or treatment period.
17. Patients should be able to tolerate the withdrawal of COPD medications during the study at the discretion of the Investigator.
18. Patient must be able to demonstrate a consistent inspiratory flow rate (≥ 40 L/min), three times consecutively using the In-Check DIAL device, mimicking the HandiHaler device setting.
19. The patient has completed diary data on a minimum of 5 days out of the last 7 days prior to randomization (not including the day of randomization) and has achieved a minimum of 70% compliance with the paper diary during the run-in period.
ExclusionCriteria
Details
1. Treatment for COPD exacerbation within 12 weeks prior to the Screening Visit (Visit 1) or 2 or more exacerbations in the last year.
2. Hospitalization for COPD or pneumonia within 12 weeks prior to the Screening Visit (Visit 1).
3. History of a life-threatening COPD episode that required intubation and/or was associated with hypercapnia, respiratory arrest, hypoxic seizures, or mMRC (Modified Medical Research Council) dyspnea Grade 4.
4. Acute (viral or bacterial) upper or lower respiratory tract infection, sinusitis, rhinitis, pharyngitis, urinary tract infection or illness within 8 weeks prior to the Screening Visit (Visit 1).
5. Use of immediate-release (Oral or IV) corticosteroids within the last 30 days and/or extended-release corticosteroids (Depot or Local) within the last 12 weeks prior to the Screening Visit (Visit 2).
6. Patients with a history of asthma or a clinical diagnosis of asthma, allergic rhinitis, or atopy; a total blood eosinophil count above 600/mm3.
7. Patients with an abnormal/clinically significant 12-lead electrocardiogram (ECG) prior to and during screening visit, during the run-in and treatment periods.
8. Patients with myocardial infarction or unstable angina in the last 12 months; unstable or life-threatening cardiac arrhythmia requiring intervention in the last 12 months; or New York Heart Association Class II-IV heart failure.
9. Patients with documented pulmonary hypertension or clinical signs of right heart failure (indicated by an increase in jugular venous pressure with or without peripheral edema) or patients who require chronic oxygen use for >12 hours per day.
10. Presence of glaucoma or a history/family history of glaucoma.
11. History of paradoxical bronchospasm, narrow-angle glaucoma, prostatic hyperplasia, bladder-neck obstruction, or any other condition, which, in the opinion of the Investigator, would contraindicate the use of an anticholinergic agent.
12. Presence or history of urinary retention.
13. Historical or current evidence of a clinically significant disease (Note: Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the patient at risk through participation, or which could affect the efficacy or safety analysis if the disease/condition exacerbated during the study) including, but not limited to:
• Cardiovascular (e.g., congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, stroke, or non-controlled arrhythmias),
• Hepatic, renal, hematological, neuropsychological, endocrine (e.g., uncontrolled diabetes mellitus, uncontrolled thyroid disorder, Addison’s disease, and Cushing’s syndrome),
• Gastrointestinal (e.g., poorly-controlled peptic ulcer disease),
• Pulmonary disease other than COPD (e.g., alpha-1 antitrypsin deficiency, active bronchiectasis, cystic fibrosis, broncho-pulmonary dysplasia, sarcoidosis, lung fibrosis, pulmonary edema, interstitial lung disease, lung or mediastinum proliferative process including malignancies).
14. Patients who have undergone thoracotomy with pulmonary resection, have plans to undergo lung transplantation or lung volume reduction therapy, or have had lung volume reduction surgery within 12 months prior to the Screening Visit (Visit 1).
15. Have any of the following conditions that, in the judgment of the Investigator, might cause participation in this study to be detrimental to the patient, including but not limited to:
• Current malignancy excluding basal cell carcinoma. (Note: History of malignancy is acceptable only if the patient has been in remission for one year prior to the Screening Visit (Visit 1). Remission is defined as no current evidence of malignancy and no treatment for the malignancy in the 5 years prior to the Screening Visit (Visit 1).
• Current or untreated tuberculosis (Note: History of tuberculosis is acceptable only if a patient has received an approved prophylactic treatment regimen or an approved active treatment regimen and has had no evidence of active disease for a minimum of 2 years).
• Uncontrolled hypertension (systolic blood pressure [BP] ≥160 or diastolic BP >100).
• Stroke within 12 months prior to the Screening Visit (Visit 1).
• Immunocompromised
16. A patient must not have any clinically significant, uncontrolled condition, or disease state that, in the opinion of the Investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
17. History of allergy or hypersensitivity to anticholinergic/muscarinic receptor antagonist agents, beta-2 adrenergic agonists, lactose/milk proteins, or specific intolerance to aerosolized tiotropium-containing products or its derivatives (e.g., ipratropium, oxitropium), or known hypersensitivity to any of the proposed ingredients or components of the delivery system.
18. History of alcohol or drug abuse within 2 years prior to the Screening Visit (Visit 1).
19. Study participation by the clinical Investigator, site employees and/or their immediate relatives.
20. Participation in any investigational drug study within the 30 days preceding the Screening Visit (Visit 1) or planned participation in another investigational drug study at any time during this study.
21. Legal incapacity or other circumstances that render the patient unable to understand the nature, scope and possible consequences of the study.
Method of Generating Random Sequence
Other
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
The area under the serial FEV1-time curve (baseline adjusted) calculated from time 0 to 24 hours (i.e., AUC0-24h) after the single dose of the treatment. Baseline is considered the pre dose FEV1 value on the day of treatment (Visit 3) prior to taking the single dose of the assigned treatment.
Two spirometry FEV1 assessments (at -60 min and -30 min pre-dose) will be performed according to ATS standards, 30 (±5) min apart. The average of the two readings will be considered as baseline FEV1.
24 Hours
Secondary Outcome
Outcome
TimePoints
The maximum FEV1 response (difference between peak FEV1 and FEV1 at baseline (pre-dose)).
24 Hours
Target Sample Size
Total Sample Size="330" Sample Size from India="165" Final Enrollment numbers achieved (Total)= "334" Final Enrollment numbers achieved (India)="197"
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 multicenter,
randomized, placebo-controlled, crossover, single dose study to demonstrate
clinical pharmacodynamic bioequivalence of tiotropium 18 μg inhalation powder,
hard capsule with spiriva®handihaler® 18 μg inhalation powder, hard capsule in
patients with chronic obstructive pulmonary disease (COPD). This study has 3
phases - Screening period, Washout
period and treatment phase (single dose in each period). At the randomization
visit, participants who meet all of the eligibility criteria will be randomised
to receive single dose of either 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).