A Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler in Pediatric Asthmatics

Asthma Clinical Trial

Official title:

A Three-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler (MDPI) Relative to Placebo in Pediatric Asthmatics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02126839
• Other study ID #: ABS-AS-303
• Status: Completed
• Phase: Phase 3
• Start date: May 2014
• Est. completion date: February 2015

Study information

• Verified date: November 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is to evaluate the chronic-dose efficacy and the safety of Albuterol MDPI compared to placebo in pediatric participants with asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 11 Years

Eligibility

Inclusion Criteria:

1. Written informed consent/assent signed and dated by the patient and/or parent/caregiver/legal guardian (as appropriate) before conducting any study related procedure

2. Male or premenarchal female 4-11 years of age, inclusive, as of the screening visit (SV)

3. Has a documented physician diagnosis of asthma per the EPR-3 Guidelines of a minimum of 6 months duration that has been stable for at least 4 weeks prior to the SV

4. Has the ability to perform spirometry reproducibly consistent with ATS guidelines and protocol-specific guidelines

5. Has FEV1 50-95% predicted for age, height and gender at the SV following a minimum 6-hour period without ß2-agonist use. (Note: Predicted values of 49.50-49.99% may be rounded up to 50% and values of 95.01-95.49% may be rounded down to 95%.)

6. Demonstrated reversible bronchoconstriction as verified by a 15% or greater increase in baseline FEV1 within 30 minutes following inhalation of 180 mcg of albuterol. (Note: Reversibility values of 14.50-14.99% may be rounded up to 15%.)

7. Is maintained on low-dose inhaled corticosteroids (ICS, less than or equal to 200 mcg of fluticasone propionate per day or equivalent), leukotriene modifiers (LTM), or inhaled cromones, and/or on short-acting ß2-agonists (SABA); as needed SABA alone is acceptable. The ICS, LTM, and cromone doses must have been stable for at least 4 weeks prior to the SV and should be maintained for the duration of the study

8. Can self-perform peak expiratory flow rate (PEF) measurements with a handheld peak flow meter

9. Can tolerate the withdrawal of applicable medications for qualification at screening

10. Otherwise in general good health, defined as 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 trial, and with a clinically acceptable 6-month medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs

11. Parents consenting are capable of understanding the requirements, risks and benefits of study participation, and, as judged by the investigator, capable of giving informed consent and being compliant with all study requirements (eg, visits, record-keeping)

12. The patient is able to correctly use the MDPI device, either alone or with assistance by a parent/guardian.

Exclusion Criteria

1. Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (eg, lactose, ethanol)

2. Participation (receiving study medication) in any investigational drug trial within the 30 days preceding the SV or planned participation in another investigational drug trial at any time during this trial

3. History of severe milk protein allergy

4. History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza) that has not resolved within 4 weeks preceding the SV

5. Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV. A patient must not have had any hospitalization for asthma within 6 months prior to the SV.

6. Initiation of immunotherapy during the study period or dose escalation during the study period. Patients being treated with immunotherapy prior to the SV must be using a stable (maintenance) dose (90 days or more) to be considered for inclusion.

7. History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures

8. Use of any prohibited concomitant medications within the washout prescribed per protocol prior to study visits

9. Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol as described in the protocol

10. The dosage of any required LTM, ICS, or inhaled cromones, has not been stable for at least 4 weeks. Intranasal corticosteroid and/or cromones have not been stable for at least two weeks prior to the SV. Allowed corticosteroid, LTM, and cromone asthma and allergy medications should be continued at the same doses during the conduct of the study.

11. Presence of any non-asthmatic acute or chronic condition, including but not limited to bronchitis, emphysema, active tuberculosis, bronchiectasis, cystic fibrosis, clinically significant cardiovascular disease (including but not limited to cardiac arrhythmias and uncontrolled hypertension), clinically significant hepatic, renal, or endocrine dysfunction, stroke, uncontrolled diabetes mellitus, hyperthyroidism, convulsive disorder, and malignancy other than basal cell carcinoma. Significant is defined as any condition that, in the opinion of the investigator, would put the safety of the patient at risk through participation, or which could affect the safety or efficacy analyses

12. Any other medical or psychological condition that in the investigator's opinion should preclude study enrollment

13. Previous participation (received MDPI study medication) in an Albuterol MDPI study

14. Study participation by clinical investigator site employees and/or their immediate relatives

15. Study participation by related or non-related individuals living in the same household, ie, only one subject per household may participate in the study at the same time.

16. Require continuous treatment with ß-blockers, MAO inhibitors, tricyclic antidepressants, anticholinergics, and/or systemic corticosteroids

17. Treated with oral or injectable corticosteroids within the 6 weeks prior to SV

18. Hospitalization for acute asthma exacerbation >2 times in 12 months prior to screening and/or received emergency room treatment other than nebulized albuterol or been hospitalized for asthma exacerbations within 6 months prior to SV

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Albuterol MDPI
90 mcg/actuation of the multidose dry powder inhaler (MDPI).
• Placebo
Matching Placebo delivered via a multidose dry powder inhaler (MDPI).
• ProAir HFA inhaler
Rescue medication, ProAir hydrofluoroalkane (HFA) inhaler, was dispensed at the run-in visit for the relief of asthma symptoms to be administered as needed.

Locations

Country	Name	City	State
Thailand	Teva Investigational Site 12533	Papillion	NE
United States	Teva Investigational Site 12515	Anaheim	California
United States	Teva Investigational Site 12496	Birmingham	Alabama
United States	Teva Investigational Site 12489	Boerne	Texas
United States	Teva Investigational Site 12524	Brooklyn	New York
United States	Teva Investigational Site 12491	Burke	Virginia
United States	Teva Investigational Site 12512	Centennial	Colorado
United States	Teva Investigational Site 12504	Charlottesville	Virginia
United States	Teva Investigational Site 12477	Cincinnati	Ohio
United States	Teva Investigational Site 12525	Cleveland	Ohio
United States	Teva Investigational Site 12505	Costa Mesa	California
United States	Teva Investigational Site 12523	Covington	Louisiana
United States	Teva Investigational Site 12486	Gainesville	Georgia
United States	Teva Investigational Site 12522	Gainesville	Florida
United States	Teva Investigational Site 12514	Greenville	South Carolina
United States	Teva Investigational Site 12507	Gresham	Oregon
United States	Teva Investigational Site 12535	Hollywood	Florida
United States	Teva Investigational Site 12476	Huntington Beach	California
United States	Teva Investigational Site 12518	Iowa City	Iowa
United States	Teva Investigational Site 12497	Lawrenceville	Georgia
United States	Teva Investigational Site 12481	Little Rock	Alaska
United States	Teva Investigational Site 12519	Los Angeles	California
United States	Teva Investigational Site 12526	Miami	Florida
United States	Teva Investigational Site 12502	Middleburg Heights	Ohio
United States	Teva Investigational Site 12484	Mission Viejo	California
United States	Teva Investigational Site 12500	Mobile	Alabama
United States	Teva Investigational Site 12501	Normal	Pennsylvania
United States	Teva Investigational Site 12509	Northfield	New Jersey
United States	Teva Investigational Site 12478	Oklahoma City	Oklahoma
United States	Teva Investigational Site 12487	Oklahoma City	Oklahoma
United States	Teva Investigational Site 12506	Oklahoma City	Oklahoma
United States	Teva Investigational Site 12474	Orangeburg	South Carolina
United States	Teva Investigational Site 12516	Orlando	Florida
United States	Teva Investigational Site 12493	Pittsburgh	Pennsylvania
United States	Teva Investigational Site 12473	Raleigh	North Carolina
United States	Teva Investigational Site 12482	Richmond	Virginia
United States	Teva Investigational Site 12498	Richmond	Virginia
United States	Teva Investigational Site 12510	Riverside	California
United States	Teva Investigational Site 12483	Rolling Hills Estates	California
United States	Teva Investigational Site 12511	Sacramento	California
United States	Teva Investigational Site 12480	Savannah	Georgia
United States	Teva Investigational Site 12508	Shiloh	Illinois
United States	Teva Investigational Site 12479	Spartanburg	South Carolina
United States	Teva Investigational Site 12490	Spokane	Washington
United States	Teva Investigational Site 12485	Stockton	California
United States	Teva Investigational Site 12517	Tamarac	Florida
United States	Teva Investigational Site 12492	Tulsa	Oklahoma
United States	Teva Investigational Site 12488	Upland	Pennsylvania
United States	Teva Investigational Site 12527	Vero Beach	Florida
United States	Teva Investigational Site 12475	Waco	Texas
United States	Teva Investigational Site 12495	Warrensburg	Missouri
United States	Teva Investigational Site 12513	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline Adjusted Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) Area Under The Concentration Time Curve Up From Time Zero up to 6 Hours (AUC0-6) Over 3 Weeks	Following measurement of the baseline FEV1 and dose administration on Days 1 and 22, FEV1 values (highest of 3 acceptable maneuvers) will be obtained at 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±10), 120 (±10), 240 (±10), and 360 (±10) minutes after the completion of dosing. Predicted FEV1 values were computed and adjusted for age, height, and gender according to Eigen et al (Eigen et al 2001) for participants 4 to 5 years of age and to Quanjer et al (Quanjer et al 1995) for participants aged 6 to 11 years using ATS criteria (American Thoracic Society/European Respiratory Society Statement 2007).	30 ±5 and 5 ±2 minutes prior to dosing, and at 5 ±2, 15 ±5, 30 ±5, 45 ±5, 60 ±10, 120 ±10, 240 ±10, and 360 ±10 minutes after completion of dosing on Days 1 and 22
Secondary	Baseline Adjusted Peak Expiratory Flow (PEF) Area Under The Concentration Time Curve Up From Time Zero up to 6 Hours (AUC0-6) Over 3 Weeks	Serial PEF measurements were obtained via spirometry. PEF measures for purpose of serial PEF assessment (pre and postdose) were collected from the spirometer assessed PEF, utilizing the values from the efforts selected based on the highest of 3 acceptable FEV1 maneuvers.	30 ±5 and 5 ±2 minutes prior to dosing, and at 5 ±2, 15 ±5, 30 ±5, 45 ±5, 60 ±10, 120 ±10, 240 ±10, and 360 ±10 minutes after completion of dosing on Days 1 and 22
Secondary	Summary of Participants With Adverse Events	Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator as mild (no limitation of usual activities), moderate, or severe (inability to carry out usual activities).; Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.	6 Months