Efficacy of Inhaled Albuterol Spiromax® in Subjects With Persistent Asthma With Steady State Pharmacokinetics
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| ClinicalTrials.gov Identifier: NCT01747629 |
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Recruitment Status :
Completed
First Posted : December 11, 2012
Results First Posted : May 21, 2015
Last Update Posted : June 26, 2015
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Asthma | Drug: Placebo MDPI Drug: Albuterol MDPI | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 160 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Study Start Date : | December 2012 |
| Actual Primary Completion Date : | October 2013 |
| Actual Study Completion Date : | November 2013 |
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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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.
Other Name: Placebo Spiromax® |
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Experimental: Albuterol MDPI
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
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Drug: 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.
Other Name: ProAir® RespiClick, Albuterol Spiromax® |
- Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period [ Time Frame: Day 1, Day 8 and 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 (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.
- Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1 [ Time Frame: 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.
- Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8 [ Time Frame: 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.
- Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85 [ Time Frame: 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.
- Participants With Adverse Events [ Time Frame: Day 1 to Day 93 ]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.
- Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group [ Time Frame: Day 1 (Baseline), Day 85 ]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.
- Participants With Clinically Significant Vital Sign Assessments [ Time Frame: Days 8 and 85 ]
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
- Maximum Observed Plasma Drug Concentration (Cmax) for Albuterol on Days 1 and 8 [ Time Frame: 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 to Observed Peak Plasma Concentration (Tmax) for Albuterol on Days 1 and 8 [ Time Frame: 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).
- 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 ]
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.
- 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 ]
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.
- 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 ]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).
- 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 ]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).
- Terminal Plasma Half-life (t1/2) for Albuterol on Days 1 and 8 [ Time Frame: 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).
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| Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01747629
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| Study Director: | Clinical Project Leader | Teva Respiratory R&D |
| Responsible Party: | Teva Branded Pharmaceutical Products R&D, Inc. |
| ClinicalTrials.gov Identifier: | NCT01747629 |
| Other Study ID Numbers: |
ABS-AS-304 |
| First Posted: | December 11, 2012 Key Record Dates |
| Results First Posted: | May 21, 2015 |
| Last Update Posted: | June 26, 2015 |
| Last Verified: | May 2015 |
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Asthma dry powder inhaler short-acting beta2-agonist SABA bronchoconstriction |
bronchodilation bronchodilator metered dose inhaler Albuterol Spiromax® |
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Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Albuterol Bronchodilator Agents Autonomic Agents |
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