Albuterol DPI (A006) Clinical Study-B2: Efficacy, Dose-Ranging and Initial Safety Evaluation

Asthma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01581177
• Other study ID #: API-A006-CL-B2
• Status: Completed
• Phase: Phase 2
• First received: April 17, 2012
• Last updated: May 18, 2017
• Start date: April 2012
• Est. completion date: August 2012

Study information

• Verified date: May 2017
• Source: Amphastar Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Albuterol DPI 25 mcg/inh
Albuterol DPI with 25 mcg Albuterol/inhalation
• Albuterol DPI 90 mcg/inh
Albuterol DPI with 90 mcg Albuterol/inhalation
• Placebo DPI
Placebo DPI with 0 mcg Albuterol/inhalation
• Albuterol MDI 90 mcg/inh
Albuterol MDI with 90 mcg Albtuerol/inhalation

Locations

Country	Name	City	State
United States	Amphastar Site 0025	Medford	Oregon
United States	Amphastar Site 0030	New Braunfels	Texas
United States	Amphastar Site 0032	San Antonio	Texas
United States	Amphastar Site 0001	San Jose	California

Sponsors (1)

Lead Sponsor	Collaborator
Amphastar Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. Review. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Visits 1-7, at baseline, 5, 20, 30, 60, 90, 120, 240, 360 minutes post-dose
Secondary	Placebo AUC of adjusted FEV1 changes	Determination of change of FEV1 in placebo arm	Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
Secondary	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	Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose
Secondary	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.	Visits 1-7, at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
Secondary	Peak bronchodilator response (Fmax)	The peak bronchodilator response (Fmax), defined as the maximum post-dose change in FEV1 percent.	Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose
Secondary	Time to peak FEV1 effect (tmax)	The time to peak FEV1 effect (tmax), defined as the time of Fmax.	Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose
Secondary	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.	Visits 1-7 at 5, 20, 30, 60, 90, 120, 180 and 360 minutes post-dose
Secondary	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.	Visits 1-7 at 60 minutes
Secondary	Dose response curve: AUC of change in percent FEV1 versus Dose	Evaluation of change in FEV1 in relation to dose.	Visits 1-7
Secondary	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.	Visits 1-7 and EOS at baseline, 3, 8, 15, 30, 90 and 360 minutes post-dose
Secondary	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.	Visits 1-7 at baseline, 10, 50 and 360 minutes post-dose
Secondary	Serum glucose	Determination of Serum glucose, at pre-dose baseline, and at 15, 35 and 120 min post-dose.	Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose
Secondary	Serum potassium	Determination of serum potassium levels, at pre-dose baseline, and at 15, 35 and 120 min post-dose.	Visits 1-7 at baseline, 15, 35 and 120 minutes post-dose
Secondary	Asthma exacerbation incidents	Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.	Visits 1-7 and EOS
Secondary	Asthma management/ rescue drug usage	Evaluation of asthma exacerbation incidents in all patients throughout the duration of the study.	Visits 1-7 and EOS
Secondary	Physical examination	Physical examination of all subjects performed at screening and end-of-study visit to evaluate subject's general health.	Screening and End-of-Study Visit
Secondary	CBC	Evaluation of CBC in all subjects at screening and end-of-study visit.	Screening and End-of-Study Visit
Secondary	Comprehensive metabolic panel	Comprehensive metabolic panel performed on all subjects at screening and end-of-study visit.	Screening and End-of-Study Visit
Secondary	Urinalysis	Urinalysis performed on all subjects at screening and end-of-study visit.	Screening and End-of-Study Visit
Secondary	Pregnancy test	A pregnancy test for women of child bearing potential at screening and end-of-study visit.	Screening and End-of-Study Visit
Secondary	Medication interactions	Evaluation of concomitant medications used by subjects throughout the study and their potential to affect the study	Screening, Visits 1-7 and End-of-Study Visit
Secondary	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.	Screening, Visits 1-7, End-of-Study Visit