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

Teva Branded Pharmaceutical Products R&D, Inc.160 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

160

Conditions

Asthma

Interventions

Placebo MDPIDRUG

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 MDPIDRUG

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.

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

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.

Locations (35)

Outcomes

Primary Outcomes

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.

Time frame: Day 1, Day 8 and Day 85

Secondary Outcomes

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.

Time frame: Day 1

Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8

Data from ClinicalTrials.gov

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Teva Investigational Site 10225

Costa Mesa, California, United States

Teva Investigational Site 10250

Encinitas, California, United States

Teva Investigational Site 10230

Huntington Beach, California, United States

Teva Investigational Site 10255

Palmdale, California, United States

Teva Investigational Site 10231

Rancho Mirage, California, United States

Teva Investigational Site 10252

Riverside, California, United States

Teva Investigational Site 10242

Rolling Hills Estates, California, United States

Teva Investigational Site 10238

San Diego, California, United States

Teva Investigational Site 10243

San Jose, California, United States

Teva Investigational Site 10247

Miami Lakes, Florida, United States

...and 25 more locations

Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85

Time frame: Day 85

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.

Time frame: Day 1 to Day 93

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.

Time frame: Day 1 (Baseline), Day 85

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

Time frame: Days 8 and 85

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).

Time frame: Days 1 and 8

Time to Observed Peak Plasma Concentration (Tmax) for Albuterol on Days 1 and 8

Time frame: Days 1 and 8

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

Time frame: Days 1 and 8

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

Time frame: Days 1 and 8

Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Infinity Post-dose(AUC0-inf) for Albuterol on Day 1

Time frame: Day 1

Area Under the Concentration-time Curve From Time 0 (Pre-dose) to 24 Hours Post-dose(AUC0-24) for Albuterol on Day 8

Time frame: Day 8

Terminal Plasma Half-life (t1/2) for Albuterol on Days 1 and 8

Time frame: Days 1 and 8