QVR: Clinical Pharmacodynamic Bioequivalence Study of Beclomethasone Dipropionate 40 mcg INH

• Sponsor: Aurobindo Pharma Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04051710
• Collaborator: (none)
• Enrollment: 1,550
• Location: 1
• Arms: 3
• Actual Duration (Months): 9.3
• Patients Per Site Per Month: 166.7

Study Details

Study Description

Brief Summary

To compare the therapeutic equivalence of Beclomethasone Dipropionate MDI (Inhalation Aerosol) 0.04 mg/ INH with the marketed QVAR® 40 mcg (Beclomethasone dipropionate hydrofluoroalkane (HFA)) and to demonstrate superiority of both active treatments over placebo.

Condition or Disease	Intervention/Treatment	Phase
Bronchial Asthma	Drug: Test Product; Drug: Reference Product; Drug: Placebo	Phase 3

Detailed Description

This study is to demonstrate the pharmacodynamic bioequivalence of the test product to the reference product in terms of improvement in FEV1 measured before and after 4 weeks of treatment in adult patients with chronic stable asthma.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1550 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate Efficacy and Safety of Beclomethasone Dipropionate Metered Dose Inhaler (Inhalation Aerosol) (0.04mg/ INH) in Male and/ or Female Subjects With Asthma
• Actual Study Start Date: Mar 12, 2019
• Actual Primary Completion Date: Aug 29, 2019
• Actual Study Completion Date: Dec 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group-I (Test) One inhalation of Beclomethasone dipropionate HFA, 0.04 mg/ INH (Test) twice daily.	Drug: Test Product; Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg; Other Names: Test
Active Comparator: Group-II (Reference) One inhalation of QVAR® 40 mcg (Beclomethasone dipropionate HFA), Inhalation Aerosol twice daily.	Drug: Reference Product; Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg; Other Names: QVAR
Placebo Comparator: Group-III (Placebo) One inhalation of Placebo Inhalation Aerosol twice daily.	Drug: Placebo; Placebo Product

Outcome Measures

Primary Outcome Measures

1. Change in FEV1 From Pre Dose to End of Treatment [4 weeks]

   Mean change in Forced Expiratory volume in 1 second (FEV 1) from baseline to end of study visit

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult male or female subjects of non-childbearing or of childbearing potential committing to consistent and correct use of an acceptable method of birth control.

2. Diagnosis of asthma as defined by the National Asthma Education and Prevention Program at least 12 months prior to screening.

3. Pre-bronchodilator FEV1 of >45% and <85% of predicted value during the screening visit and on the first day of treatment.

4. 15% and >0.20 L reversibility of FEV1 within 30 minutes following 360 mcg of albuterol inhalation (pMDI).

5. Patients should be stable on their chronic asthma treatment regimen for at least four weeks prior to enrollment.

6. Currently non-smoking; had not used tobacco products (i.e., cigarettes, cigars, pipe tobacco) within the past year, and having had <10 pack-years of historical use.

7. Ability to replace current short-acting β agonist (SABAs) with salbutamol/albuterol inhaler for use as needed for the duration of the study. Subjects should be able to withhold all inhaled SABAs for at least six hours prior to lung function assessments on study visits.

8. Ability to discontinue their asthma medications (inhaled corticosteroids and long-acting β agonists) during the run-in period and for remainder of the study.

9. Willingness to give their written informed consent to participate in the study.

Exclusion Criteria:

1. Life-threatening asthma, defined as a history of asthma episodes(s) requiring intubation, and/or associated with hypercapnia, respiratory arrest or hypoxic seizures, asthma related syncopal episode(s), or hospitalizations within the past year prior to the screening or during the run-in period.

2. Significant respiratory disease other than asthma (COPD, interstitial lung disease, etc.)

3. Evidence or history of clinically significant disease or abnormality including congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infarction, or cardiac dysrhythmia. In addition, historical or current evidence of significant hematologic, hepatic, neurologic, psychiatric, renal, or other diseases that, in the opinion of the investigator, would put the patient at risk through study participation, or would affect the study analyses if the disease exacerbates during the study.

4. Viral or bacterial, upper or lower respiratory tract infection, or sinus, or middle ear infection within four weeks prior to the screening, during the run-in period, or on the day of treatment.

5. Hypersensitivity to any sympathomimetic drug (e.g., albuterol) or any inhaled, intranasal, or systemic corticosteroid therapy.

6. Patients receiving β2-blockers, anti-arrhythmics, anti-depressants, and monoamine oxidase inhibitors within 4 weeks prior to the screening.

7. Patients who required systemic corticosteroids (for any reason) within the past 2 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maharashtra Medical Foundation Joshi Hospital	Pune	Maharashtra	India	411004

Sponsors and Collaborators

• Aurobindo Pharma Ltd

Investigators

• Study Director: Joseph Marialouis, Aurobindo Pharma USA Inc

Study Documents (Full-Text)

• Study Protocol - Aug 7, 2019
• Statistical Analysis Plan - Oct 23, 2019

More Information

Publications

None provided.

• Responsible Party: Aurobindo Pharma Ltd
• ClinicalTrials.gov Identifier: NCT04051710
• Other Study ID Numbers: CR176-17
• First Posted: Aug 9, 2019
• Last Update Posted: Nov 13, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Arm/Group Title	Group I (Test)	Group II	Group III (Placebo)
Arm/Group Description	One inhalation of Beclomethasone dipropionate HFA, 0.04 mg/ INH (Test) twice daily. Test Product: Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg	One inhalation of Beclomethasone dipropionate HFA, 0.04 mg/ INH (Reference) twice daily. Reference Product: QVAR® Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg	One inhalation of Placebo inhalation aerosol twice daily.
Period Title: Overall Study
STARTED	620	620	310
COMPLETED	616	612	306
NOT COMPLETED	4	8	4

Baseline Characteristics

Arm/Group Title	Test Group	Reference Group	Placebo Group	Total
Arm/Group Description	Subjects randomly enrolled into test group received test comparator, Beclomethasone dipropinate, 0.04 mg/INH to administer one inhalation twice daily	Subjects randomly enrolled into Reference group received Reference comparator, QVAR® containing Beclomethasone dipropinate, 0.04 mg/INH to administer one inhalation twice daily	Subjects randomly enrolled into Placebo group received a Placebo device to administer one inhalation twice daily	Total of all reporting groups
Overall Participants	617	615	308	1540
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41 (12.71)	41.8 (12.85)	40.6 (12.86)	41.2 (12.8)
Sex: Female, Male (Count of Participants)
Female	267 43.3%	272 44.2%	139 45.1%	678 44%
Male	350 56.7%	343 55.8%	169 54.9%	862 56%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	617 100%	615 100%	308 100%	1540 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
India	617 100%	615 100%	308 100%	1540 100%

Outcome Measures

1. Primary Outcome

Title	Change in FEV1 From Pre Dose to End of Treatment
Description	Mean change in Forced Expiratory volume in 1 second (FEV 1) from baseline to end of study visit
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Mean change of FEV1 from baseline to end of study was measured

Arm/Group Title	Group-I (Test)	Group-II (Reference)	Group-III (Placebo)
Arm/Group Description	One inhalation of Beclomethasone dipropionate HFA, 0.04 mg/ INH (Test) twice daily. Test Product: Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg	One inhalation of QVAR® 40 mcg (Beclomethasone dipropionate HFA), Inhalation Aerosol twice daily. Reference Product: Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg	One inhalation of Placebo Inhalation Aerosol twice daily. Placebo: Placebo Product
Measure Participants	577	566	282
Least Squares Mean (Standard Error) [Litres]	0.23 (0.01)	0.22 (0.01)	0.09 (0.01)

Adverse Events

Time Frame	1 year
Arm/Group Title	Group I (Test)		Group II (Reference)		Group III (Placebo)
Arm/Group Description	One inhalation of Beclomethasone dipropionate HFA, 0.04 mg/ INH (Test) twice daily. Test Product: Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg		One inhalation of Beclomethasone dipropionate HFA, 0.04 mg/ INH (Reference) twice daily. Reference Product: QVAR® Beclomethasone Dipropionate Inhalation Aerosol, 40 mcg		One inhalation of Placebo inhalation aerosol twice daily.
All Cause Mortality
	Group I (Test)		Group II (Reference)		Group III (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/619 (0%)		0/620 (0%)		0/310 (0%)
Serious Adverse Events
	Group I (Test)		Group II (Reference)		Group III (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/619 (0%)		0/620 (0%)		0/310 (0%)
Other (Not Including Serious) Adverse Events
	Group I (Test)		Group II (Reference)		Group III (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/619 (6.3%)		25/620 (4%)		18/310 (5.8%)
Blood and lymphatic system disorders
Anaemia	7/619 (1.1%)		5/620 (0.8%)		3/310 (1%)
Leukocytosis	0/619 (0%)		0/620 (0%)		1/310 (0.3%)
Thrombocytopenia	1/619 (0.2%)		0/620 (0%)		2/310 (0.6%)
Gastrointestinal disorders
Abdominal Pain	1/619 (0.2%)		0/620 (0%)		0/310 (0%)
Constipation	0/619 (0%)		1/620 (0.2%)		0/310 (0%)
Diarrhoea	2/619 (0.3%)		0/620 (0%)		0/310 (0%)
Gastritis	0/619 (0%)		0/620 (0%)		1/310 (0.3%)
Hyperchlorhydria	0/619 (0%)		2/620 (0.3%)		0/310 (0%)
Nausea	2/619 (0.3%)		1/620 (0.2%)		2/310 (0.6%)
Vomiting	1/619 (0.2%)		1/620 (0.2%)		0/310 (0%)
General disorders
Asthenia	1/619 (0.2%)		0/620 (0%)		0/310 (0%)
Inflammation	0/619 (0%)		1/620 (0.2%)		0/310 (0%)
Pain	3/619 (0.5%)		0/620 (0%)		1/310 (0.3%)
Pyrexia	5/619 (0.8%)		0/620 (0%)		0/310 (0%)
Infections and infestations
Rhinitis	1/619 (0.2%)		0/620 (0%)		1/310 (0.3%)
Investigations
Alanine Aminotransferase increased	1/619 (0.2%)		1/620 (0.2%)		1/310 (0.3%)
Aspartate Aminotransferase increased	1/619 (0.2%)		1/620 (0.2%)		1/310 (0.3%)
Alkaline phosphatase increased	1/619 (0.2%)		0/620 (0%)		1/310 (0.3%)
white blood cells decreased	1/619 (0.2%)		1/620 (0.2%)		0/310 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/619 (0%)		1/620 (0.2%)		0/310 (0%)
Pain in extremity	1/619 (0.2%)		0/620 (0%)		0/310 (0%)
Nervous system disorders
Headache	13/619 (2.1%)		7/620 (1.1%)		4/310 (1.3%)
Tremor	0/619 (0%)		1/620 (0.2%)		0/310 (0%)
Vertigo	1/619 (0.2%)		0/620 (0%)		0/310 (0%)
Psychiatric disorders
Insomnia	1/619 (0.2%)		1/620 (0.2%)		0/310 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/619 (0.2%)		1/620 (0.2%)		2/310 (0.6%)
Vascular disorders
Migraine	1/619 (0.2%)		0/620 (0%)		0/310 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the ownership of all the data generated from the study and PI has no rights to publish the results or any information derived from the study.