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This study evaluates the efficacy, dose-ranging and safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 110 to 220 mcg per dose in comparison to a DPI Placebo Control and an Albuterol metered dose inhaler (MDI) Active Control.
This study is designed to evaluate the efficacy and safety profiles of A006 and to assist in identifying the optimum dose of A006 for future clinical studies. Proventil® HFA MDI, a currently marketed Albuterol MDI product, will be used as an Active Control. The study also employs a Placebo Control DPI, which has the same configuration as the A006 DPI except that it contains no active ingredient.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment T1 | Active Comparator | One inhalation of 110 mcg A006 DPI. Total 110 mcg. |
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| Treatment T2 | Active Comparator | One inhalation of 220 mcg A006 DPI. Total 220 mcg. |
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| Placebo | Placebo Comparator | One inhalation of placebo DPI . Total 0 mcg |
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| Treatment R1 | Active Comparator | One inhalation of Proventil® MDI Total 90 mcg |
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| Treatment R2 | Active Comparator | Two inhalations of Proventil® MDI, 180 mcg total |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| A006 DPI | Drug | Single dose 110 mcg, 1 inhalation |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Percentage Change (∆%FEV1) from the Same-Day Pre-Dose Baseline | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule. Statistical analysis is performed using a one-sided t-test. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve (AUC[0-6h]) of Placebo Adjusted Post-Dose FEV1 Percentage Change (∆∆%FEV1) from the Same-Day Pre-Dose Baseline | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. ∆∆FEV1% for the study visit is calculated by subtracting the mean ∆%FEV1 for subjects in a randomized treatment arm from their ∆%FEV1. Area under the curve (AUC), from baseline to 6 hours post-dose, for the study visit is calculated using the trapezoidal rule. |
| Measure | Description | Time Frame |
|---|---|---|
| Systolic and Diastolic Blood Pressure (SBP/DBP) at Screening | Subjects have their vital signs, i.e., blood pressure and heart rate, measured prior to reversibility dosing and 30 minutes after dosing during the Screening Visit. | Within 30 minutes prior to reversibility dosing (baseline) and 30 minutes post-reversibility dosing |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Safety Monitor | Amphastar Pharmeceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amphastar Site 0001 | San Jose | California | 95117 | United States | ||
| Amphastar Site 0025 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9695144 | Background | Lipworth BJ, Clark DJ. Lung delivery of salbutamol given by breath activated pressurized aerosol and dry powder inhaler devices. Pulm Pharmacol Ther. 1997 Aug;10(4):211-4. doi: 10.1006/pupt.1997.0093. | |
| 16185368 | Background | Ahrens RC. The role of the MDI and DPI in pediatric patients: "Children are not just miniature adults". Respir Care. 2005 Oct;50(10):1323-8; discussion 1328-30. |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D000420 | Albuterol |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| A006 DPI | Drug | Single dose 220 mcg, 1 inhalation |
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| Placebo DPI | Other | Placebo, 1 inhalation |
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| Proventil® MDI | Drug | Single dose 90 mcg, 1 inhalation |
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| Proventil® MDI | Drug | Single dose 90 mcg, 2 inhalations |
|
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| Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 Volume Changes (∆FEV1) from the Same-Day Pre-Dose Baseline | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Time to Onset of Bronchodilator Effect (t[onset]) | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. t[onset] is the point where post-dose ∆%FEV1 first reaches ≥ 12% over the pre-dose baseline. Determined by linear interpolation. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Peak Bronchodilator Response (F[max]) | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. F[max] is the maximum post-dose ∆%FEV1. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Time to Peak ∆FEV1 Effect (t[max]) | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. The time to peak ∆FEV1 effect, t[max], is defined as the time of F[max]. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Area Under the Curve (AUC[0-6h]) of Post-Dose FEV1 in Volume from the Same-Day Pre-Dose Baseline | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Area under the curve (AUC), from baseline to 6 hours post-dose, for the treatment period is calculated using the trapezoidal rule. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| F[max] of Post-Dose FEV1 in Volume | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. F[max] of post-dose FEV1 in volume is the maximum post-dose FEV1. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Efficacy Duration-1 | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-1 is total duration of bronchodilator effects when ∆%FEV1 is ≥ 12% above the baseline. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Efficacy Duration-2 | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-2 is total duration of bronchodilator effects when ∆FEV1 is ≥ 200 mL above the baseline. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Efficacy Duration-3 | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Efficacy Duration-3 is total duration of bronchodilator effects when ∆FEV1 is ≥ 100 mL above the baseline. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Bronchodilator Response | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. Subjects that demonstrate a ≥ 12% increase for ∆%FEV1 will be classified as having a bronchodilator response. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Dose Response Curve | The forced expiratory volume in the 1st second (FEV1) is measured with a clinically accepted model of spirometer. Subjects perform a pre-dose baseline FEV1 prior to dosing and perform subsequent FEV1 tests at 5, 15 and 30 minutes and 1, 1.5, 2, 3, 4, 5, and 6 hours after dosing during each treatment period. The dose response curve is the AUC[0-6h] of ∆%FEV1 versus study drug dosage. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Systolic and Diastolic Blood Pressure (SBP/DBP) |
Subjects have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at 15 and 30 minutes and 1, 1.5, 2, and 6 hours post-dose during each treatment period. |
| Within 1 hour prior to dosing (baseline) to 6 hours post-dose |
| Heart Rate (HR) at Screening | Subjects have their vital signs, i.e., blood pressure and heart rate, measured prior to reversibility dosing and 30 minutes after dosing during the Screening Visit. | Within 30 minutes prior to reversibility dosing (baseline) and 30 minutes post-reversibility dosing |
| Heart Rate (HR) | Subjects have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at 15 and 30 minutes and 1, 1.5, 2, and 6 hours post-dose during each treatment period. | Within 1 hour prior to dosing (baseline) to 6 hours post-dose |
| 12-Lead ECG QT/QTc Intervals at Screening | 12-Lead ECGs are performed to measure QT and QTc intervals prior to reversibility dosing during the Screening Visit. | Within 1 hour prior to reversibility dosing |
| 12-Lead ECG QT/QTc Intervals | 12-Lead ECGs are performed to measure QT and QTc intervals prior to dosing and at 30 minutes and 1, 2, and 6 hours post-dose during each treatment period. | Within 1 hour prior to dosing (baseline) to 6 hours post-dose |
| Number of Subjects with Incidents of Asthma Exacerbation | An asthma exacerbation incident is defined as significant worsening of clinical symptoms that cannot be adequately relieved by the rescue medication, or significant deterioration of FEV1 tests combined with clinical symptoms. Investigators monitor worsening of asthma symptoms during the treatment period and determine if subjects had experienced an asthma exacerbation. | Participants will be followed for the duration of the study, an expected average of 3 weeks |
| Number of Subjects that Used Rescue Drug | Rescue medication may be used to control worsening or exacerbations of asthma symptoms during the study visits when necessary, as determined by the investigator. | Within 30 minutes prior to dosing (baseline) to 6 hours post-dose |
| Complete Blood Count (CBC) at Screening | A CBC is performed as part of the subject safety evaluations with differentials including: red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and white blood cell types (WBC). | Within 1 hour after reversibility dosing |
| Complete Blood Count (CBC) at End-of-Study | A CBC is performed as part of the subject safety evaluations with differentials including: red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and white blood cell types (WBC). | 120 minutes post-dose at Visit 5 (within 57 days after Visit 1) |
| Comprehensive Metabolic Panel (CMP) at Screening | A CMP is performed as part of the subject safety evaluations looking at levels for the following: total protein (albumin/globulin), sodium, chloride, potassium, glucose, calcium, carbon dioxide (CO2), blood urea nitrogen (BUN), creatinine, alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and bilirubin. | Within 1 hour after reversibility dosing |
| Comprehensive Metabolic Panel (CMP) at End-of-Study | A CMP is performed as part of the subject safety evaluations looking at levels for the following: total protein (albumin/globulin), sodium, chloride, potassium, glucose, calcium, carbon dioxide (CO2), blood urea nitrogen (BUN), creatinine, alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and bilirubin. | 120 minutes post-dose at Visit 5 (within 57 days after Visit 1) |
| Urinalysis at Screening | Routine and microscopic urinalysis is performed as part of the subject safety evaluations to measure urine pH and specific gravity. | Within 1 hour after reversibility dosing |
| Urinalysis at End-of-Study | Routine and microscopic urinalysis is performed as part of the subject safety evaluations to measure urine pH and specific gravity. | 120 minutes post-dose at Visit 5 (within 57 days after Visit 1) |
| Incidents of Pregnancy at Screening | A urinary pregnancy test was performed for women of child-bearing potential as a part of the Screening Visit evaluations to determine the eligibility of the subject for the study. | Within 1 hour prior to reversibility dosing |
| Incidents of Pregnancy at End-of-Study | A urinary pregnancy test was performed for women of child-bearing potential as a part of the End-of-Study safety evaluations to determine if a pregnancy had occurred during the study. | At or after 120 minutes post-dose at Visit 5 (within 57 days after Visit 1) |
| Concomitant Medication Usage | Concomitant medications used by subjects throughout the duration of the study, from 30 days prior to Screening to End-of-Study evaluations, are recorded by the investigators. The total number of times a specific concomitant medication is used during the study is summarized. | Participants will be followed for the duration of the study, an expected average of 3 weeks |
| Medford |
| Oregon |
| 97504 |
| United States |
| Amphastar Site 0030 | New Braunfels | Texas | 78130 | United States |
| Amphastar Site 0032 | San Antonio | Texas | 78229 | United States |
| 3653233 | Background | Goldstein DA, Tan YK, Soldin SJ. Pharmacokinetics and absolute bioavailability of salbutamol in healthy adult volunteers. Eur J Clin Pharmacol. 1987;32(6):631-4. doi: 10.1007/BF02456001. |
| 7874928 | Background | Hindle M, Newton DA, Chrystyn H. Dry powder inhalers are bioequivalent to metered-dose inhalers. A study using a new urinary albuterol (salbutamol) assay technique. Chest. 1995 Mar;107(3):629-33. doi: 10.1378/chest.107.3.629. |
| 16264058 | Background | Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, Coates A, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson DC, MacIntyre N, McKay R, Miller MR, Navajas D, Pedersen OF, Wanger J. Interpretative strategies for lung function tests. Eur Respir J. 2005 Nov;26(5):948-68. doi: 10.1183/09031936.05.00035205. No abstract available. |
| 7271065 | Background | Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981 Jun;123(6):659-64. doi: 10.1164/arrd.1981.123.6.659. |
| 7074238 | Background | Crapo RO, Morris AH, Clayton PD, Nixon CR. Lung volumes in healthy nonsmoking adults. Bull Eur Physiopathol Respir. 1982 May-Jun;18(3):419-25. |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000588 |
| Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |