Back to resultsAlbuterol DPI (A006) Clinical Study-B2: Efficacy, Dose-Ranging and Initial Safety Evaluation
Primary Purpose
Asthma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Albuterol DPI 25 mcg/inh
Albuterol DPI 90 mcg/inh
Placebo DPI
Albuterol MDI 90 mcg/inh
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring asthma, mild-to-moderate persistent asthma, mild asthma, moderate asthma, persistent asthma
Eligibility Criteria
Inclusion Criteria:
- Generally healthy, male and female adults, 18-55 years of age at screening
- With mild-to-moderate persistent asthma for at least 6 months prior to screening and having used a beta-agonist(s) inhaler
- Demonstrate a Forced Expiratory Volume (FEV1) at 50-85 percent of predicted normal during screening baseline measurement
- Demonstrate an airway reversibility of greater than or equal to 15 percent within 30 minutes of inhaling 2 inhalations of Proventil MDI during screening visit
- Demonstrate Peak Inspiratory Flow Rate (PIF) within 80-150 L/min (after training), at least 2 times consecutively
- Demonstrate ability to use a DPI and MDI inhaler properly after training
- Females must be not pregnant, not lactating, and using a clinically acceptable form of birth control
- Properly agree to participate in the trial
Exclusion Criteria:
- A smoking history of more than or equal to 10 years or having smoked within 6 months of screening visit
- Upper respiratory tract infections within 2 weeks or lower respiratory tract infection within 4 weeks prior to screening visit
- Asthma exacerbations that required emergency care or a hospital stay within 4 weeks prior to screening visit
- Any current or recent respiratory tract infections that might affect the response to the study drug as determined by the investigator, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema and other significant respiratory diseases besides asthma
- Current clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant or other illnesses that could impact the study as determined by the investigator
- Known intolerance or hypersensitivity to any ingredients of the study drug DPI or Proventil MDI (i.e.: Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid and ethanol)
Sites / Locations
- Amphastar Site 0001
- Amphastar Site 0025
- Amphastar Site 0030
- Amphastar Site 0032
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Active Comparator
Active Comparator
Arm Label
T1
T2
T3
T4
P
R1
R2
Arm Description
Two inhalations, one of Albuterol DPI 25 mcg/inh and one of Placebo DPI; Total Albuterol dose of 25 mcg
Two inhalations of Albuterol DPI 25 mcg/inh; Total Albuterol dose of 50 mcg
Two inhalations, one of Albuterol DPI 90 mcg/inh and one of Placebo DPI; Total Albuterol dose of 90 mcg
Two inhalations of Albuterol DPI 90 mcg/inh; Total Albuterol dose of 180 mcg
Two inhalations Placebo DPI; Total Albuterol dose of 0 mcg
One inhalation of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 90 mcg
Two inhalations of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 180 mcg
Outcomes
Primary Outcome Measures
Change in FEV1 Area Under the Curve (AUC) versus placebo
Serial FEV1 measurements to demonstrate the mean AUC change in percent FEV1 from same-day baseline of A006 versus placebo control
Secondary Outcome Measures
Placebo AUC of adjusted FEV1 changes
Determination of change of FEV1 in placebo arm
AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7
Determination of FEV1 volume change from pre-dose baseline to post treatment at Visit 7
Time post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline
Time to onset of bronchodilator effect (Tonset), determined by linear interpolation as the point where post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline.
Peak bronchodilator response (Fmax)
The peak bronchodilator response (Fmax), defined as the maximum post-dose change in FEV1 percent.
Time to peak FEV1 effect (tmax)
The time to peak FEV1 effect (tmax), defined as the time of Fmax.
Duration of effect
Duration of effect, calculated as the total duration of bronchodilator effects when change in FEV1 percent is greater than or equal to 12 percent above baseline.
Bronchodilatory Response Rate (R percent)
Evaluation of Bronchodilatory Response Rate (R percent) of responders who demonstrate a greater than or equal to 12 percent increase for change in FEV1 percent during the initial 60 min post-dose.
Dose response curve: AUC of change in percent FEV1 versus Dose
Evaluation of change in FEV1 in relation to dose.
Vital Signs (i.e.: blood pressure and heart rate)
Vital signs, i.e. blood pressure (SBP/DBP) and heart rate (HR), at pre-dose baseline, and 3, 8, 15, 30, 90, and 360 min post-dose.
12-lead ECG (for routine and QT/QTc)
Measurement of 12-lead ECG (for routine and QT/QTc), at pre-dose baseline, and at 10, 50, and 360 min post-dose.
Serum glucose
Determination of Serum glucose, at pre-dose baseline, and at 15, 35 and 120 min post-dose.
Serum potassium
Determination of serum potassium levels, at pre-dose baseline, and at 15, 35 and 120 min post-dose.
Asthma exacerbation incidents
Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.
Asthma management/ rescue drug usage
Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.
Physical examination
Physical examination of all subjects performed at screening and end-of-study visit to evaluate subject's general health.
CBC
Evaluation of CBC in all subjects at screening and end-of-study visit.
Comprehensive metabolic panel
Comprehensive metabolic panel performed on all subjects at screening and end-of-study visit.
Urinalysis
Urinalysis performed on all subjects at screening and end-of-study visit.
Pregnancy test
A pregnancy test for women of child bearing potential at screening and end-of-study visit.
Medication interactions
Evaluation of concomitant medications used by subjects throughout the study and their potential to affect the study
Number of participants with adverse events as a measure of safety and tolerability
Adverse drug events whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary.
Full Information
NCT ID
NCT01581177
First Posted
April 17, 2012
Last Updated
May 18, 2017
Sponsor
Amphastar Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01581177
Brief Title
Albuterol DPI (A006) Clinical Study-B2: Efficacy, Dose-Ranging and Initial Safety Evaluation
Official Title
A Randomized, Double- or Evaluator-blind, Active- and Placebo-controlled, Single Dose, Seven-arm, Crossover Dose-ranging Study of A006 in Adult Asthma Patients
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amphastar Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main objective of this study is to evaluate the efficacy, dose-ranging and initial safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 25 to 180 mcg per dosing in comparison to a DPI Placebo Control and an Albuterol metered dose inhaler (MDI) Active Control.
This study will be conducted in male and female adult patients who have mild-to-moderate persistent asthma for at least 6 months, but are otherwise generally healthy.
Detailed Description
The main objective of this study is to evaluate the efficacy, dose-ranging and initial safety profiles of A006, an Albuterol dry powder inhaler (DPI), in the dose range of 25 to 180 mcg per dose in comparison to the DPI Placebo Control and the Active (Reference) Control. The study results of this study together with that of A006-B study will be utilized to determine the optimum final dose range of A006 for further clinical studies.
The study will be conducted in male and female adult patients who have mild-to-moderate persistent asthma but are otherwise generally healthy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
asthma, mild-to-moderate persistent asthma, mild asthma, moderate asthma, persistent asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
T1
Arm Type
Experimental
Arm Description
Two inhalations, one of Albuterol DPI 25 mcg/inh and one of Placebo DPI; Total Albuterol dose of 25 mcg
Arm Title
T2
Arm Type
Experimental
Arm Description
Two inhalations of Albuterol DPI 25 mcg/inh; Total Albuterol dose of 50 mcg
Arm Title
T3
Arm Type
Experimental
Arm Description
Two inhalations, one of Albuterol DPI 90 mcg/inh and one of Placebo DPI; Total Albuterol dose of 90 mcg
Arm Title
T4
Arm Type
Experimental
Arm Description
Two inhalations of Albuterol DPI 90 mcg/inh; Total Albuterol dose of 180 mcg
Arm Title
P
Arm Type
Placebo Comparator
Arm Description
Two inhalations Placebo DPI; Total Albuterol dose of 0 mcg
Arm Title
R1
Arm Type
Active Comparator
Arm Description
One inhalation of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 90 mcg
Arm Title
R2
Arm Type
Active Comparator
Arm Description
Two inhalations of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 180 mcg
Intervention Type
Drug
Intervention Name(s)
Albuterol DPI 25 mcg/inh
Intervention Description
Albuterol DPI with 25 mcg Albuterol/inhalation
Intervention Type
Drug
Intervention Name(s)
Albuterol DPI 90 mcg/inh
Intervention Description
Albuterol DPI with 90 mcg Albuterol/inhalation
Intervention Type
Drug
Intervention Name(s)
Placebo DPI
Intervention Description
Placebo DPI with 0 mcg Albuterol/inhalation
Intervention Type
Drug
Intervention Name(s)
Albuterol MDI 90 mcg/inh
Intervention Description
Albuterol MDI with 90 mcg Albtuerol/inhalation
Primary Outcome Measure Information:
Title
Change in FEV1 Area Under the Curve (AUC) versus placebo
Description
Serial FEV1 measurements to demonstrate the mean AUC change in percent FEV1 from same-day baseline of A006 versus placebo control
Time Frame
Visits 1-7, at baseline, 5, 20, 30, 60, 90, 120, 240, 360 minutes post-dose
Secondary Outcome Measure Information:
Title
Placebo AUC of adjusted FEV1 changes
Description
Determination of change of FEV1 in placebo arm
Time Frame
Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
Title
AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7
Description
Determination of FEV1 volume change from pre-dose baseline to post treatment at Visit 7
Time Frame
Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose
Title
Time post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline
Description
Time to onset of bronchodilator effect (Tonset), determined by linear interpolation as the point where post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline.
Time Frame
Visits 1-7, at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
Title
Peak bronchodilator response (Fmax)
Description
The peak bronchodilator response (Fmax), defined as the maximum post-dose change in FEV1 percent.
Time Frame
Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose
Title
Time to peak FEV1 effect (tmax)
Description
The time to peak FEV1 effect (tmax), defined as the time of Fmax.
Time Frame
Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
Title
Duration of effect
Description
Duration of effect, calculated as the total duration of bronchodilator effects when change in FEV1 percent is greater than or equal to 12 percent above baseline.
Time Frame
Visits 1-7 at 5, 20, 30, 60, 90, 120, 180 and 360 minutes post-dose
Title
Bronchodilatory Response Rate (R percent)
Description
Evaluation of Bronchodilatory Response Rate (R percent) of responders who demonstrate a greater than or equal to 12 percent increase for change in FEV1 percent during the initial 60 min post-dose.
Time Frame
Visits 1-7 at 60 minutes
Title
Dose response curve: AUC of change in percent FEV1 versus Dose
Description
Evaluation of change in FEV1 in relation to dose.
Time Frame
Visits 1-7
Title
Vital Signs (i.e.: blood pressure and heart rate)
Description
Vital signs, i.e. blood pressure (SBP/DBP) and heart rate (HR), at pre-dose baseline, and 3, 8, 15, 30, 90, and 360 min post-dose.
Time Frame
Visits 1-7 and EOS at baseline, 3, 8, 15, 30, 90 and 360 minutes post-dose
Title
12-lead ECG (for routine and QT/QTc)
Description
Measurement of 12-lead ECG (for routine and QT/QTc), at pre-dose baseline, and at 10, 50, and 360 min post-dose.
Time Frame
Visits 1-7 at baseline, 10, 50 and 360 minutes post-dose
Title
Serum glucose
Description
Determination of Serum glucose, at pre-dose baseline, and at 15, 35 and 120 min post-dose.
Time Frame
Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose
Title
Serum potassium
Description
Determination of serum potassium levels, at pre-dose baseline, and at 15, 35 and 120 min post-dose.
Time Frame
Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose
Title
Asthma exacerbation incidents
Description
Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.
Time Frame
Visits 1-7 and EOS
Title
Asthma management/ rescue drug usage
Description
Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.
Time Frame
Visits 1-7 and EOS
Title
Physical examination
Description
Physical examination of all subjects performed at screening and end-of-study visit to evaluate subject's general health.
Time Frame
Screening and End-of-Study Visit
Title
CBC
Description
Evaluation of CBC in all subjects at screening and end-of-study visit.
Time Frame
Screening and End-of-Study Visit
Title
Comprehensive metabolic panel
Description
Comprehensive metabolic panel performed on all subjects at screening and end-of-study visit.
Time Frame
Screening and End-of-Study Visit
Title
Urinalysis
Description
Urinalysis performed on all subjects at screening and end-of-study visit.
Time Frame
Screening and End-of-Study Visit
Title
Pregnancy test
Description
A pregnancy test for women of child bearing potential at screening and end-of-study visit.
Time Frame
Screening and End-of-Study Visit
Title
Medication interactions
Description
Evaluation of concomitant medications used by subjects throughout the study and their potential to affect the study
Time Frame
Screening, Visits 1-7 and End-of-Study Visit
Title
Number of participants with adverse events as a measure of safety and tolerability
Description
Adverse drug events whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary.
Time Frame
Screening, Visits 1-7, End-of-Study Visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Generally healthy, male and female adults, 18-55 years of age at screening
With mild-to-moderate persistent asthma for at least 6 months prior to screening and having used a beta-agonist(s) inhaler
Demonstrate a Forced Expiratory Volume (FEV1) at 50-85 percent of predicted normal during screening baseline measurement
Demonstrate an airway reversibility of greater than or equal to 15 percent within 30 minutes of inhaling 2 inhalations of Proventil MDI during screening visit
Demonstrate Peak Inspiratory Flow Rate (PIF) within 80-150 L/min (after training), at least 2 times consecutively
Demonstrate ability to use a DPI and MDI inhaler properly after training
Females must be not pregnant, not lactating, and using a clinically acceptable form of birth control
Properly agree to participate in the trial
Exclusion Criteria:
A smoking history of more than or equal to 10 years or having smoked within 6 months of screening visit
Upper respiratory tract infections within 2 weeks or lower respiratory tract infection within 4 weeks prior to screening visit
Asthma exacerbations that required emergency care or a hospital stay within 4 weeks prior to screening visit
Any current or recent respiratory tract infections that might affect the response to the study drug as determined by the investigator, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema and other significant respiratory diseases besides asthma
Current clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, malignant or other illnesses that could impact the study as determined by the investigator
Known intolerance or hypersensitivity to any ingredients of the study drug DPI or Proventil MDI (i.e.: Albuterol, sulfate, lactose, milk protein, HFA-134a, oleic acid and ethanol)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Safety Monitor
Organizational Affiliation
Amphastar Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Amphastar Site 0001
City
San Jose
State/Province
California
ZIP/Postal Code
95117
Country
United States
Facility Name
Amphastar Site 0025
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
Facility Name
Amphastar Site 0030
City
New Braunfels
State/Province
Texas
ZIP/Postal Code
78130
Country
United States
Facility Name
Amphastar Site 0032
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
9695144
Citation
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.
Results Reference
background
PubMed Identifier
16185368
Citation
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.
Results Reference
background
PubMed Identifier
3653233
Citation
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.
Results Reference
background
PubMed Identifier
7874928
Citation
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.
Results Reference
background
PubMed Identifier
7271065
Citation
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.
Results Reference
background
PubMed Identifier
7074238
Citation
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.
Results Reference
background
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Albuterol DPI (A006) Clinical Study-B2: Efficacy, Dose-Ranging and Initial Safety Evaluation
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