Efficacy of Inhaled Albuterol Spiromax® in Subjects With Persistent Asthma With Steady State Pharmacokinetics

Asthma Clinical Trial

Official title:

A 12-week Comparison of the Efficacy and Safety and Steady-State Pharmacokinetics of Albuterol Spiromax® Versus Placebo in Subjects 12 Years and Older With Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01747629
• Other study ID #: ABS-AS-304
• Status: Completed
• Phase: Phase 3
• First received: December 7, 2012
• Last updated: May 28, 2015
• Start date: December 2012
• Est. completion date: November 2013

Study information

• Verified date: May 2015
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the efficacy of Albuterol Spiromax® versus placebo in subjects with persistent asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: November 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent/assent

• At least 12 years of age at screening

• General good health

• Persistent asthma for =3 months, with an FEV1 50-80% predicted and =15% reversibility

• Taking inhaled corticosteroids at a stable dose (= equivalent of 500mcg of fluticasone propionate/day) for at least 4 weeks prior to the Screening Visit.

• Ability to perform spirometry in an acceptable manner as per protocol guidelines

• Other inclusion criteria apply

Exclusion Criteria:

• A known hypersensitivity to albuterol or any of the excipients in the formulations.

• History of a respiratory infection or disorder that has not resolved within 1 week preceding the Screening Visit (SV).

• History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation.

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

• Hospitalization due to asthma exacerbation 2 or more times in the past year

• Initiation of immunotherapy or dose escalation during the study period

• Other exclusion criteria apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Placebo MDPI
Placebo MDPI administered as 2 inhalations 4 times a day (QID) (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 12 weeks.
• Albuterol MDPI
Albuterol MDPI administered as 2 inhalations 4 times a day (QID) (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 12 weeks.

Locations

Country	Name	City	State
United States	Teva Investigational Site 10257	Baltimore	Maryland
United States	Teva Investigational Site 10253	Bangor	Maine
United States	Teva Investigational Site 10229	Bellevue	Nebraska
United States	Teva Investigational Site 10240	Bethlehem	Pennsylvania
United States	Teva Investigational Site 10244	Charlotte	North Carolina
United States	Teva Investigational Site 10248	Cincinnati	Ohio
United States	Teva Investigational Site 10225	Costa Mesa	California
United States	Teva Investigational Site 10250	Encinitas	California
United States	Teva Investigational Site 10232	Eugene	Oregon
United States	Teva Investigational Site 10235	Fall River	Massachusetts
United States	Teva Investigational Site 10230	Huntington Beach	California
United States	Teva Investigational Site 10259	Medford	Oregon
United States	Teva Investigational Site 10247	Miami Lakes	Florida
United States	Teva Investigational Site 10226	Minneapolis	Minnesota
United States	Teva Investigational Site 10233	Minneapolis	Minnesota
United States	Teva Investigational Site 10236	North Dartmouth	Massachusetts
United States	Teva Investigational Site 10249	Oklahoma City	Oklahoma
United States	Teva Investigational Site 10255	Palmdale	California
United States	Teva Investigational Site 10246	Pittsburgh	Pennsylvania
United States	Teva Investigational Site 10256	Pittsburgh	Pennsylvania
United States	Teva Investigational Site 10237	Portland	Oregon
United States	Teva Investigational Site 10231	Rancho Mirage	California
United States	Teva Investigational Site 10252	Riverside	California
United States	Teva Investigational Site 10227	Rochester	New York
United States	Teva Investigational Site 10251	Rock Hill	South Carolina
United States	Teva Investigational Site 10242	Rolling Hills Estates	California
United States	Teva Investigational Site 10258	San Antonio	Texas
United States	Teva Investigational Site 10238	San Diego	California
United States	Teva Investigational Site 10243	San Jose	California
United States	Teva Investigational Site 10245	Seattle	Washington
United States	Teva Investigational Site 10228	Spartanburg	South Carolina
United States	Teva Investigational Site 10241	St. Louis	Missouri
United States	Teva Investigational Site 10239	Tallahassee	Florida
United States	Teva Investigational Site 10234	Tampa	Florida
United States	Teva Investigational Site 10254	White Marsh	Maryland

Sponsors (1)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period	FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day.; FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.	Day 1, Day 8 and Day 85	No
Secondary	Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1	FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day.; FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.	Day 1	No
Secondary	Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8	FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day.; FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.	Day 8	No
Secondary	Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85	FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day.; FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.	Day 85	No
Secondary	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 on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily 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.	Day 1 to Day 93	Yes
Secondary	Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group	Physical exam was recorded as normal or abnormal based on physician assessment. Format for results is: Test Baseline/Endpoint. HEENT = head, eyes, ears, nose, throat.	Day 1 (Baseline), Day 85	Yes
Secondary	Participants With Clinically Significant Vital Sign Assessments	For both standard and serial vital signs, participants were seated for at least 5 minutes before vital signs were assessed. Heart rate was obtained prior to the blood pressure measurement. Serial heart rate and blood pressure were conducted in the sitting position prior to the spirometry assessment; baseline measures were taken pre-dose at -30 ± 5 and -5 minutes on Day 1. Day 85 serial vital sign measures were taken in the sitting position prior to spirometry assessments pre-dose at -30 ± 5 and -5 minutes, then post-dose at 30 (±5) minutes, 1hr (± 10 min), 2hr (± 10 min), 3hr (± 10 min), 4hr (± 10 min), 5hr (± 10 min) and 6 hr (± 10 min).; Serial heart rate and blood pressure measurements that were elevated to the following criteria were considered clinically significant: Systolic blood pressure: > 160 beats/minute Diastolic blood pressure: >100 beats/minute Heart rate: >120 beats/minute	Days 8 and 85	Yes
Secondary	Maximum Observed Plasma Drug Concentration (Cmax) for Albuterol on Days 1 and 8	Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).	Days 1 and 8	No
Secondary	Time to Observed Peak Plasma Concentration (Tmax) for Albuterol on Days 1 and 8	Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).	Days 1 and 8	No
Secondary	Area Under the Concentration-time Curve From Time 0 (Pre-dose) up to 6 Hours Post-dose (AUC0-6) for Albuterol on Days 1 and 8	Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).; AUC0-6 on Day 8 is not from pre-dose but at steady state.	Days 1 and 8	No
Secondary	Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) for Albuterol on Days 1 and 8	Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).; AUC0-t on Day 8 is not from pre-dose but at steady state.	Days 1 and 8	No
Secondary	Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Infinity Post-dose(AUC0-inf) for Albuterol on Day 1	Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).	Day 1	No
Secondary	Area Under the Concentration-time Curve From Time 0 (Pre-dose) to 24 Hours Post-dose(AUC0-24) for Albuterol on Day 8	Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).	Day 8	No
Secondary	Terminal Plasma Half-life (t1/2) for Albuterol on Days 1 and 8	Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).	Days 1 and 8	No