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

NCT01581177 | Completed Phase 2

• 1 other identifier: API-A006-CL-B2
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

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.

Conditions

Asthma

Keywords

asthma; mild-to-moderate persistent asthma; mild asthma; moderate asthma; persistent asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (21)

• Placebo AUC of adjusted FEV1 changes

  Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose

• AUC of post-dose FEV1 volume changes from pre-dose baseline to Visit 7

  Visits 1-7 at baseline, 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose

• Time 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

• Peak bronchodilator response (Fmax)

  Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240, 360 minutes post-dose

• Time to peak FEV1 effect (tmax)

  Visits 1-7 at 5, 20, 30, 60, 90, 120, 180, 240 and 360 minutes post-dose

Study Arms (7)

T1

EXPERIMENTAL

Two inhalations, one of Albuterol DPI 25 mcg/inh and one of Placebo DPI; Total Albuterol dose of 25 mcg

Drug: Albuterol DPI 25 mcg/inh; Drug: Placebo DPI

T2

EXPERIMENTAL

Two inhalations of Albuterol DPI 25 mcg/inh; Total Albuterol dose of 50 mcg

Drug: Albuterol DPI 25 mcg/inh

T3

EXPERIMENTAL

Two inhalations, one of Albuterol DPI 90 mcg/inh and one of Placebo DPI; Total Albuterol dose of 90 mcg

Drug: Albuterol DPI 90 mcg/inh; Drug: Placebo DPI

T4

EXPERIMENTAL

Two inhalations of Albuterol DPI 90 mcg/inh; Total Albuterol dose of 180 mcg

Drug: Albuterol DPI 90 mcg/inh

P

PLACEBO COMPARATOR

Two inhalations Placebo DPI; Total Albuterol dose of 0 mcg

Drug: Placebo DPI

R1

ACTIVE COMPARATOR

One inhalation of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 90 mcg

Drug: Albuterol MDI 90 mcg/inh

R2

ACTIVE COMPARATOR

Two inhalations of Albuterol MDI 90 mcg/inh; Total Albuterol dose of 180 mcg

Drug: Albuterol MDI 90 mcg/inh

Interventions

Albuterol DPI 25 mcg/inh DRUG

Albuterol DPI with 25 mcg Albuterol/inhalation

T1; T2

Albuterol DPI 90 mcg/inh DRUG

Albuterol DPI with 90 mcg Albuterol/inhalation

T3; T4

Placebo DPI DRUG

Placebo DPI with 0 mcg Albuterol/inhalation

P; T1; T3

Albuterol MDI 90 mcg/inh DRUG

Albuterol MDI with 90 mcg Albtuerol/inhalation

R1; R2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amphastar Pharmaceuticals, Inc.: lead

Study Sites (4)

Amphastar Site 0001

San Jose, California, 95117, United States

Location

Amphastar Site 0025

Medford, Oregon, 97504, United States

Location

Amphastar Site 0030

New Braunfels, Texas, 78130, United States

Location

Amphastar Site 0032

San Antonio, Texas, 78229, United States

Location

Related Publications (6)

• 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.

  PMID: 9695144 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.

  PMID: 16185368 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.

  PMID: 3653233 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.

  PMID: 7874928 BACKGROUND

• 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.

  PMID: 7271065 BACKGROUND

• 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.

  PMID: 7074238 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

Isoniazid

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Safety Monitor

  Amphastar Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2012
• First Posted: April 20, 2012
• Study Start: April 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: August 1, 2012
• Last Updated: May 19, 2017

Record last verified: 2017-05

Locations

US (4)