| CTRI Number |
CTRI/2021/10/037214 [Registered on: 08/10/2021] Trial Registered Prospectively |
| Last Modified On: |
11/10/2021 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
Pilot Study to Demonstrate the Pharmacodynamic
equivalence of Albuterol Sulfate Inhalation Aerosol EQ 90 mcg Base/Inh
(of Macleods Pharmaceuticals Ltd.)in
Adult Patients with Stable Mild Asthma. |
|
Scientific Title of Study
|
A Prospective, Randomized, Single-Dose, Double-Blind, Double-
Dummy, Four-Period, Four-Sequence, Four-Treatment, Placebo and
Active Controlled, Comparative, Multicenter, Crossover
Bronchoprovocation Pilot Study to Demonstrate the Pharmacodynamic
equivalence of Albuterol Sulfate Inhalation Aerosol EQ 90 mcg Base/Inh
(of Macleods Pharmaceuticals Ltd.) to Proair® HFA (Albuterol Sulfate)
Inhalation Aerosol EQ 90 mcg Base/Inh (Teva Respiratory, LLC) in
Adult Patients with Stable Mild Asthma. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CT-011-ALBU-2020 Version Date: 2.0 16-Aug-2021 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Ashish Mungantiwar |
| Designation |
Executive President Medical Services & Head Clinical Trials |
| Affiliation |
Macleods Pharmaceuticals Ltd |
| Address |
Macleods Pharmaceuticals Ltd R and D III Plot No 18 Street No 9 Marol MIDC Andheri East
Mumbai (Suburban)
MAHARASHTRA
400093
India |
| Phone |
02248890100 |
| Fax |
02229256229 |
| Email |
drashish@macleodspharma.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Ashish Mungantiwar |
| Designation |
Executive President Medical Services & Head Clinical Trials |
| Affiliation |
Macleods Pharmaceuticals Ltd |
| Address |
Macleods Pharmaceuticals Ltd R and D III Plot No 18 Street No 9 Marol MIDC Andheri East
Mumbai (Suburban)
MAHARASHTRA
400093
India |
| Phone |
02248890100 |
| Fax |
02229256229 |
| Email |
drashish@macleodspharma.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Ashish Mungantiwar |
| Designation |
Executive President Medical Services & Head Clinical Trials |
| Affiliation |
Macleods Pharmaceuticals Ltd |
| Address |
Macleods Pharmaceuticals Ltd R and D III Plot No 18 Street No 9 Marol MIDC Andheri East
Mumbai (Suburban)
MAHARASHTRA
400093
India |
| Phone |
02248890100 |
| Fax |
02229256229 |
| Email |
drashish@macleodspharma.com |
|
|
Source of Monetary or Material Support
|
| MACLEODS PHARMACEUTICALS LTD |
|
|
Primary Sponsor
|
| Name |
MACLEODS PHARMACEUTICALS LTD |
| Address |
MACLEODS PHARMACEUTICALS LTD.
R & D III, Plot No. 18, Street No. 9, MIDC Area
Andheri-(East), Mumbai 400 093, India.
Tel.: 91-22-48890100 |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Vaibhav pandharkar |
Shree Hospital |
Clinial Trial Department , Survey no 7/3/B Gulmohar Society Near Rakshak Nagar Phase 1 Behind Hotel Radisson Kharadi Pune 411014
Pune
MAHARASHTRA |
02046941111
drvaibhavpandharkar@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Ethics Committee Jehangir Clinical Development Centre Pvt ltd |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: J453||Mild persistent asthma, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Albuterol sulfate inhalation aerosol (180 mcg Base/Inh) |
Reference product: Albuterol sulfate inhalation aerosol (180 mcg Base/Inh)- Duration 1 day in any one of the four periods (period 1 , period 2, period 3, or period 4). Each period has washout of a minimum of 24 hours and a maximum of 7 days. |
| Comparator Agent |
Albuterol sulfate inhalation
aerosol (90 mcg Base/Inh) |
Reference product (Proair HFA): Albuterol sulfate inhalation aerosol (90 mcg Base/Inh)- Duration 1 day in any one of the four periods (period 1, period 2, period 3, or period 4). Each period has washout of a minimum of 24 hours and a maximum of 7 days. |
| Intervention |
Albuterol sulfate inhalation aerosol (90 mcg Base/Inh) |
Test Product (T): Albuterol sulfate inhalation aerosol (90 mcg Base/Inh) - Duration 1 day in any one of the four periods (period 1, period 2, period 3, or period 4). Each period has washout of a minimum of 24 hours and a maximum of 7 days.) |
| Comparator Agent |
Placebo Inhaler |
Placebo Inhaler similar to Test Product- Duration 1 day in all four periods (period 1 , period 2, period 3, period 4). Each period has washout of a minimum of 24 hours and a maximum of 7 days. |
| Comparator Agent |
Placebo inhaler |
Reference Placebo (Rp): Placebo Inhaler similar to Reference product: Duration 1 day any three periods (period 1, period 2, period 3, or period 4). Each period has washout of a minimum of 24 hours and a maximum of 7 days. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or non-pregnant, non-lactating female aged between 18 to 65 years (both inclusive)
2. Stable mild asthmatics based on National Asthma Education and Prevention Program
(NAEPP) guidelines
3. Forced expiratory volume in one second (FEV1) more than or equal to 80% of predicted
4. Airway responsiveness to methacholine demonstrated by pre-albuterol-dose (baseline)
PC20 less than or equal to 8 mg/mL
5. Non-smokers for at least six months prior to study and a maximum smoking history of
five-pack years (the equivalent of one pack per day for five years)
6. Able to demonstrate correct use of the pressurized metered dose inhaler using the training
kit provided
7. Must be able to perform acceptable and repeatable spirometry as per American Thoracic
Society (ATS) guidelines
8. Able to provide written informed consent and willing to comply with all aspects of the
trial |
|
| ExclusionCriteria |
| Details |
1. Known intolerance or hypersensitivity to active or inactive ingredient of the
investigational products or saline or methacholine chloride
2. Evidence of upper or lower respiratory tract infection, e.g. pneumonia, bronchitis,
sinusitis, within six weeks prior to study
3. History of seasonal asthma exacerbation in which case the subject should be studied
outside of relevant allergen season
4. History of cystic fibrosis, bronchiectasis or other respiratory diseases
5. History of cardiovascular, renal, neurologic, liver or endocrine dysfunction, including ECG with evidence of ischemic heart disease
6. Treatment in an emergency room or hospitalization for acute asthmatic symptoms or need for daily oral corticosteroids within past three months
7. History of severe exacerbation in the last one year prior to screening and mild to
moderate exacerbations in the last 6 weeks prior to screening
8. Inability to tolerate or unwillingness to comply with required washout periods or unable
to temporarily withdraw applicable asthma-medications and/or follow life-style
restrictions (e.g. restriction of xanthine containing foods and beverages) prior to screening and each study period
9. Abnormal prolongation of QT/QTc-interval (males: >430 ms and females: >450 ms)
and/or any other clinically significant electrocardiogram (ECG) abnormalities which in
the opinion of the investigator may affect subject’s safety during the study or interfere
with the study results
10. Serum potassium levels and random blood sugar levels outside the range (serum
potassium range: 3.7 to 5.2 mEq/L; random blood sugar range: 80 to 140 mg/dL) and
hemoglobin A1c (HbA1c) more than 8%
11. Males or females planning pregnancy during the study duration
12. Males or females of childbearing potential not willing to use adequate and consistent
contraception methods during the study period
13. Positive serology test results at screening for human immunodeficiency virus (HIV) I and
HIV II, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) at screening
14. Subjects who have been treated in a clinical trial with an investigational drug or
investigational device within a period of 90 days prior to screening
15. Any clinically significant acute or chronic illness that could compromise the integrity of
study data or affect the analyses if the disease exacerbates during the study or place the subject at risk by participating in the study
16. Any elective, pre-planned or scheduled surgery or hospitalizations prior to start of the study
17. Subjects with history of surgery within six weeks prior to screening, which in the opinion
of the investigator interferes with study treatment results or affects the safety of the
subject during the study
18. Known history of drug/substance abuse |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Pre-numbered or coded identical Containers |
|
Blinding/Masking
|
Double Blind Double Dummy |
|
Primary Outcome
|
| Outcome |
TimePoints |
Post-dose PD20 which is a provocative dose (PD) of methacholine challenge agent
required to reduce the forced expiratory volume in one second (FEV1) by 20%
following administration of differing doses of Albuterol or Placebo inhalation
o The 20% reduction in FEV1 is determined relative to saline FEV1 measured
before the Placebo or Albuterol administration |
Post dose at Period 1, 2, 3, and 4 (Time frame: 15-min after last inhalation of study treatment] |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Post-dose PC20 which is a provocative concentration (PC) of methacholine challenge
agent required to reduce the FEV1 by 20% following administration of differing doses
of Albuterol or Placebo inhalation |
Post dose at Period 1, 2, 3, and 4 a total of approximately 4 weeks. |
|
|
Target Sample Size
|
Total Sample Size="24"
Sample Size from India="24"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
10/10/2021 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0"
Months="4"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Investigational Products/Study Treatments Test Product (T): Albuterol sulfate inhalation aerosol (90 mcg Base/Inh) (of Macleods Pharmaceuticals Ltd.) Reference Product (R): Proair® HFA Albuterol sulfate inhalation aerosol (90 mcg Base/Inh) (Teva Respiratory, LLC) Test Placebo (Tp): Placebo Inhaler similar to Test Product Reference Placebo (Rp): Placebo Inhaler similar to Proair® HFA
Study treatments: • Zero dose, •90 mcg of R, •180 mcg of R, •90 mcg of T
Planned Study Sites - The trial is planned to be conducted at approximately 4 sites in India.
Study Population - 24 randomized males and non-pregnant females with stable mild asthma as per National Asthma Education and Prevention Program (NAEPP) guidelines will be included.
Study Design/Methodology - This is a prospective, randomized, single-dose, double-blind, double-dummy, four-period, four-sequence, four-treatment, placebo and active-controlled, comparative, multicenter, crossover bronchoprovocation pilot study to demonstrate the pharmacodynamic equivalence of Albuterol sulfate inhalation aerosol, EQ 90 mcg Base/Inh (Macleods Pharmaceuticals Ltd.) to Proair® HFA (albuterol sulfate) inhalation aerosol, EQ 90 mcg Base/Inh (Teva Respiratory, LLC) in adult patients with stable mild asthma.
Safety objective - Safety and tolerability of the investigational product (IP)
Methacoline challenge, saline control, and spirometry - A methacoline challenge testing procedures as per ATS requirements will be followed in the study.
Primary Pharmacodynamic Endpoint - Post-dose PD20 which is a provocative dose (PD) of methacholine challenge agent required to reduce the forced expiratory volume in one second (FEV1) by 20% following administration of differing doses of Albuterol or Placebo inhalation
Secondary Pharmacodynamic Endpoint - Post-dose PC20 which is a provocative concentration (PC) of methacholine challenge agent required to reduce the FEV1 by 20% following administration of differing doses of Albuterol or Placebo inhalation
Safety Endpoints - Incidence of adverse events during the study period Clinically significant change in serum potassium, random blood sugar (RBS), vital signs and 12-lead electrocardiogram (ECG) recordings during the study period
|