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The objective of this study is to evaluate the pharmacokinetics (PK) and safety profiles of A006, an Albuterol dry powder inhaler (DPI), following a single dose of 110 mcg (T1) or 220 mcg (T2), in healthy male and female adult volunteers.
This study is a randomized, double or evaluator-blinded, single dose, four-arm, crossover PK study in eighteen (18) healthy volunteers, both male and female adults, at 18-40 years of age.
All candidates will be screened and only those who satisfy all enrollment criteria will be enrolled into this study. Each study subject will participate in a screening visit and four (4) study visits with one (1) randomized study treatment given in each visit.
PK samples will be analyzed with an established LC/MS/MS method. An End-of-Study (EOS) safety evaluation will be conducted at the end of Study Visit-4.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment T1 | Experimental | One inhalation of 110 mcg A006 DPI. Total 110 mcg |
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| Treatment T2 | Experimental | One inhalation of 220 mcg A006 DPI. Total 220 mcg. |
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| Treatment R1 | Active Comparator | One inhalation of 90 mcg Proventil® MDI. Total 90 mcg. |
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| Treatment R2 | Active Comparator | Two inhalations of 90 mcg Proventil® MDI. Total 180 mcg |
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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 of Drug Concentration versus Time (AUC[0-t]) | Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Area under the curve of the drug concentration versus time curve (AUC[0-t]) for each treatment period will be calculated using the trapezoidal rule. | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
| Peak Plasma Concentration (C[max]) | Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Peak plasma concentration (C[max]) will be the highest concentration of Albuterol during each treatment period. | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
| Time to Reach Peak Plasma Concentration (t[max]) | Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Time to reach peak plasma concentration (t[max]) will be the time it takes to reach the highest concentration of Albuterol during each treatment period. | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
| Plasma Albuterol Concentrations at All Time Points | Subject PK blood samples will be taken prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. PK samples will be analyzed using a validated test method. Plasma Albuterol concentrations at these time points will be reported during each treatment period. | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
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| Measure | Description | Time Frame |
|---|---|---|
| Systolic Blood Pressure (SBP) at Screening | Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy. | Within 14 days prior to Day 1 (Visit 1) |
| Systolic Blood Pressure (SBP) |
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 0035 | Cypress | California | 90630 | United States |
| 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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| 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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Subject will have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. |
| Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
| Diastolic Blood Pressure (DBP) at Screening | Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy. | Within 14 days prior to Day 1 (Visit 1) |
| Diastolic Blood Pressure (DBP) | Subject will have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
| Heart Rate (HR) at Screening | Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy. | Within 14 days prior to Day 1 (Visit 1) |
| Heart Rate (HR) | Subject will have their vital signs, i.e., blood pressure and heart rate, measured prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
| 12-Lead ECG QT Intervals at Screening | 12-Lead ECGs will be performed to measure QT and QTc intervals during the Screening Visit to ensure absence of overt cardiac illnesses. | Within 14 days prior to Day 1 (Visit 1) |
| 12-Lead ECG QT Intervals | 12-Lead ECGs will be performed to measure QT and QTc intervals prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
| 12-Lead ECG QTc Intervals at Screening | 12-Lead ECGs will be performed to measure QT and QTc intervals during the Screening Visit to ensure absence of overt cardiac illnesses. | Within 14 days prior to Day 1 (Visit 1) |
| 12-Lead ECG QTc Intervals | 12-Lead ECGs will be performed to measure QT and QTc intervals prior to dosing and at multiple time points, up to 8 hours after dosing during each treatment period. | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose |
| Complete Blood Count (CBC) at Screening | A CBC will be performed as part of the subject safety evaluations at screening. | Within 14 days prior to Day 1 (Visit 1) |
| Complete Blood Count (CBC) at End-of-Study | A CBC will be performed as part of the End-of-Study subject safety evaluations at end-of-study. | 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) |
| Comprehensive Metabolic Panel (CMP) at Screening | A CMP will be performed as part of the subject safety evaluations at screening. | Within 14 days prior to Day 1 (Visit 1) |
| Comprehensive Metabolic Panel (CMP) at End-of-Study | A CMP will be performed as part of the End-of-Study subject safety evaluations at end-of-study. | 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) |
| Urinalysis at Screening | Routine and microscopic urinalysis will be performed as part of the subject safety evaluations at screening. | Within 14 days prior to Day 1 (Visit 1) |
| Urinalysis at End-of-Study | Routine and microscopic urinalysis will be performed as part of the End-of-Study subject safety evaluations at end-of-study. | 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) |
| Incidents of Pregnancy at Screening | A urinary pregnancy test will be 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 14 days prior to Day 1 (Visit 1) |
| Incidents of Pregnancy at End-of-Study | A urinary pregnancy test will be 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. | 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) |
| Serious Adverse Events | Adverse drug events (ADEs), whether observed by investigators or reported by the subjects, will be documented, evaluated, followed up, and treated if deemed necessary. According to FDA guidelines, a serious ADE will refer to any adverse drug experience occurring at any dose that results in any of the following outcomes: 1) death; 2) a life-threatening adverse drug experience; 3) inpatient hospitalization or prolongation of existing hospitalization; 4) persistent or significant disability/incapacity; 5) congenital anomaly/birth defect; 6) other important medical events that may jeopardize the subject or may require medical or surgical intervention to prevent one of the outcomes listed in this definition. ADEs will be followed until stabilized/resolved or 30 days from the date the subject has finished the study, whichever is sooner. | Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks |
| Other Adverse Events | Adverse drug events (ADEs), whether observed by investigators or reported by the subjects, will be documented, evaluated, followed up, and treated if deemed necessary. ADEs will be followed until stabilized/resolved or 30 days from the date the subject has finished the study, whichever is sooner. | Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks |
| 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. |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000588 |
| Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |