Clinical trial NCT01581177: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: asthma
mild-to-moderate persistent asthma
mild asthma
moderate asthma
persistent asthma
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-04-20
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Change in FEV1 Area Under the Curve (AUC) versus placebo
timeFrame: Visits 1-7, at baseline, 5, 20, 30, 60, 90, 120, 240, 360 minutes post-dose
Secondary outcomes:
measure: Placebo AUC of adjusted FEV1 changes
timeFrame: Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
measure: AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7
timeFrame: Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose
measure: Time post-dose change in FEV1 percent first reaches greater than or equal to 12 percent over the Pre-dose Baseline
timeFrame: Visits 1-7, at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
measure: Peak bronchodilator response (Fmax)
timeFrame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose
measure: Time to peak FEV1 effect (tmax)
timeFrame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
measure: Duration of effect
timeFrame: Visits 1-7 at 5, 20, 30, 60, 90, 120, 180 and 360 minutes post-dose
measure: Bronchodilatory Response Rate (R percent)
timeFrame: Visits 1-7 at 60 minutes
measure: Dose response curve: AUC of change in percent FEV1 versus Dose
timeFrame: Visits 1-7
measure: Vital Signs (i.e.: blood pressure and heart rate)
timeFrame: Visits 1-7 and EOS at baseline, 3, 8, 15, 30, 90 and 360 minutes post-dose
measure: 12-lead ECG (for routine and QT/QTc)
timeFrame: Visits 1-7 at baseline, 10, 50 and 360 minutes post-dose
measure: Serum glucose
timeFrame: Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose
measure: Serum potassium
timeFrame: Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose
measure: Asthma exacerbation incidents
timeFrame: Visits 1-7 and EOS
measure: Asthma management/ rescue drug usage
timeFrame: Visits 1-7 and EOS
measure: Physical examination
timeFrame: Screening and End-of-Study Visit
measure: CBC
timeFrame: Screening and End-of-Study Visit
measure: Comprehensive metabolic panel
timeFrame: Screening and End-of-Study Visit
measure: Urinalysis
timeFrame: Screening and End-of-Study Visit
measure: Pregnancy test
timeFrame: Screening and End-of-Study Visit
measure: Medication interactions
timeFrame: Screening, Visits 1-7 and End-of-Study Visit
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Screening, Visits 1-7, End-of-Study Visit
Other outcomes:
Locations:
city: San Jose
country: United States
facility: Amphastar Site 0001
state: California
city: Medford
country: United States
facility: Amphastar Site 0025
state: Oregon
city: New Braunfels
country: United States
facility: Amphastar Site 0030
state: Texas
city: San Antonio
country: United States
facility: Amphastar Site 0032
state: Texas
Study officials:
affiliation: Amphastar Pharmaceuticals, Inc.
name: Safety Monitor
role: STUDY_DIRECTOR
References:
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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.
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.
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.
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.
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.