Asthma
Conditions
Keywords
Asthma, Albuterol
Brief summary
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.
Detailed description
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.
Interventions
DRUGA006 DPI
Single dose 110 mcg, 1 inhalation
DRUGProventil® MDI
Single dose 90 mcg, 1 inhalation
Sponsors
Amphastar Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Generally healthy, male and female adults, 18-40 years of age at Screening; * Having no clinically significant respiratory, cardiovascular and other systemic or organic illnesses; * Body weight ≥ 50 kg for men and ≥ 45 kg for women, and BMI within the range of 18.5 - 30.0 kg/m2 inclusive; * Sitting blood pressure ≤ 135/90 mmHg; * Demonstrating negative HIV, HBsAg and HCV tests, alcohol and nine panel urine drug screen tests; * Demonstrating proficiency in the use of DPI and MDI or able to be trained in the proper use of these devices; * Demonstrating Peak Inspiratory Flow Rate (PIF) within 80-150 L/min (after training), for at least 2 times consecutively, with a maximum of 5 attempts; * Having no known hypersensitivity to any ingredients of A006 and Proventil® MDI (Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid, or ethanol). (Subjects must be able to tolerate at least one teaspoon of milk); * Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control; and * Having properly consented and satisfied all other inclusion/
Exclusion criteria
as required for this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of Drug Concentration versus Time (AUC[0-t]) | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
| Peak Plasma Concentration (C[max]) | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
| Time to Reach Peak Plasma Concentration (t[max]) | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
| Plasma Albuterol Concentrations at All Time Points | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate (HR) at Screening | Within 14 days prior to Day 1 (Visit 1) | Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy. |
| Heart Rate (HR) | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
| 12-Lead ECG QT Intervals at Screening | Within 14 days prior to Day 1 (Visit 1) | 12-Lead ECGs will be performed to measure QT and QTc intervals during the Screening Visit to ensure absence of overt cardiac illnesses. |
| 12-Lead ECG QT Intervals | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
| 12-Lead ECG QTc Intervals at Screening | Within 14 days prior to Day 1 (Visit 1) | 12-Lead ECGs will be performed to measure QT and QTc intervals during the Screening Visit to ensure absence of overt cardiac illnesses. |
| 12-Lead ECG QTc Intervals | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
| Complete Blood Count (CBC) at Screening | Within 14 days prior to Day 1 (Visit 1) | A CBC will be performed as part of the subject safety evaluations at screening. |
| Complete Blood Count (CBC) at End-of-Study | 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) | A CBC will be performed as part of the End-of-Study subject safety evaluations at end-of-study. |
| Systolic Blood Pressure (SBP) at Screening | Within 14 days prior to Day 1 (Visit 1) | Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy. |
| Comprehensive Metabolic Panel (CMP) at End-of-Study | 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) | A CMP will be performed as part of the End-of-Study subject safety evaluations at end-of-study. |
| Urinalysis at Screening | Within 14 days prior to Day 1 (Visit 1) | Routine and microscopic urinalysis will be performed as part of the subject safety evaluations at screening. |
| Urinalysis at End-of-Study | 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) | Routine and microscopic urinalysis will be performed as part of the End-of-Study subject safety evaluations at end-of-study. |
| Incidents of Pregnancy at Screening | Within 14 days prior to Day 1 (Visit 1) | 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. |
| Incidents of Pregnancy at End-of-Study | 4 hours post-dose at Visit 4 (within 6 weeks after Day 1 (Visit 1)) | 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. |
| Serious Adverse Events | Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks | 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. |
| Other Adverse Events | Signing of Informed Consent at Screening Visit to End-of-Study Visit, an expected average of 7 Weeks | 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. |
| Comprehensive Metabolic Panel (CMP) at Screening | Within 14 days prior to Day 1 (Visit 1) | A CMP will be performed as part of the subject safety evaluations at screening. |
| Systolic Blood Pressure (SBP) | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
| Diastolic Blood Pressure (DBP) at Screening | Within 14 days prior to Day 1 (Visit 1) | Subjects will have their vital signs, i.e., blood pressure and heart rate, measured during the Screening Visit to ensure they are generally healthy. |
| Diastolic Blood Pressure (DBP) | Within 30 minutes prior to dosing (baseline) to 8 hours post-dose | 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. |
Countries
United States
Outcome results
None listed