Pharmacokinetic and Pharmacodynamic Profiles of Albuterol Spiromax® and ProAir® Hydrofluoroalkane (HFA) in Pediatric Patients With Asthma

Comparison of the Pharmacokinetic and Pharmacodynamic Profiles of Albuterol Spiromax® and ProAir® HFA in Pediatric Patients With Persistent Asthma

The primary objective of this study is to compare the pharmacokinetic (PK) profiles of Albuterol Spiromax® and ProAir HFA after administration of a single inhaled dose of 180 mcg albuterol base from each product.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Albuterol Spiromax®; Drug: ProAir® HFA

Detailed Description

This is a single center, open-label, 2-period crossover study. The study consists of a screening visit followed by a treatment period comprising 2 treatment visits. The treatment period visits will be separated by a 4 to 14-day washout period. Eligible patients will be kept overnight prior to each treatment period.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, United States
      • Teva Investigational Site 10538

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent/assent signed and dated by the patient and/or parent/caregiver/legal guardian (as appropriate) before conducting any study-related procedure.
2. Male or pre-menarchal female patient 4-11 years of age, inclusive, as of the Screening Visit (SV)
3. Has a documented physician diagnosis of persistent asthma of a minimum of 3 months duration that has been stable for at least 4 weeks prior to the SV. The asthma diagnosis must be in accordance with the National Asthma Education and Prevention Program Guidelines Expert Panel Report 3 (EPR3).
4. Forced expiratory volume in 1 second (FEV1) >80% predicted for age, height and gender and race at the SV based on the pediatric population standards.
5. Any patient being treated with inhaled corticosteroids (ICS) must be on a lowdose regimen (200 mcg or less of fluticasone propionate per day or equivalent), which has been stable for at least 4 weeks prior to the SV and which is expected to be maintained for the duration of the study
6. Has required less than 4 inhalations per week of a rescue bronchodilator (on average) for the 4 weeks preceding the SV

7. Has the ability to withhold inhaled albuterol for at least 72 hours preceding each Treatment Visit (TV).

   • Other criteria apply, including must weigh at least 45 pounds

Exclusion Criteria:

1. A known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (lactose, ethanol, etc.)
2. Participation (receiving study drug) in any investigational drug trial within the 30 days preceding the SV or planned participation in another investigational drug trial at any time during this trial
3. History of severe milk protein allergy
4. Proneness to orthostatic dysregulation, syncope, or blackouts
5. History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza) that has not resolved within 2 weeks preceding the SV.
6. History of life-threatening asthma or that is defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures

7. Any asthma exacerbation requiring systemic corticosteroids within 3 months of the SV. A patient must not have had any hospitalization for asthma within 6 months prior to the SV.

   • Other criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Spiromax/ProAir; Single dose of Albuterol Spiromax® 180 mcg followed by a 4 to 14 day washout period then a single dose of ProAir® HFA 180 mcg	Drug: Albuterol Spiromax®; Albuterol Spiromax® 180 mcg (administered as 2 actuations of 90 mcg of albuterol base/actuation ex-mouthpiece) orally inhaled, single dose; Other Names: Spiromax®; Drug: ProAir® HFA; ProAir® HFA 180 mcg (administered as 2 actuations of 90 mcg of albuterol base/actuation ex-mouthpiece) orally inhaled, single dose; Other Names: ProAir®
EXPERIMENTAL: ProAir/Spiromax; Single dose of ProAir® HFA 180 mcg followed by a 4 to 14 day washout period then a single dose of Albuterol Spiromax® 180 mcg	Drug: Albuterol Spiromax®; Albuterol Spiromax® 180 mcg (administered as 2 actuations of 90 mcg of albuterol base/actuation ex-mouthpiece) orally inhaled, single dose; Other Names: Spiromax®; Drug: ProAir® HFA; ProAir® HFA 180 mcg (administered as 2 actuations of 90 mcg of albuterol base/actuation ex-mouthpiece) orally inhaled, single dose; Other Names: ProAir®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma albuterol concentration-time curve	Blood samples for plasma albuterol concentration determination will be drawn 5 (±2) minutes prior to dosing and at 30 (±2), 60 (±5), 120 (±10), 360 (±10), and 600 (±10) minutes after the completion of dosing.	Time 0 to the last detectable plasma albuterol concentration measured up to 10 hours post-dose (AUC0-t)
Maximum observed plasma albuterol concentration (Cmax)	Blood samples for plasma albuterol concentration determination will be drawn 5 (±2) minutes prior to dosing and at 30 (±2), 60 (±5), 120 (±10), 360 (±10), and 600 (±10) minutes after the completion of dosing.	From baseline to up to 10 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamic Effect on Vital Signs	Effects on vital signs (blood pressure, pulse rate) over 6 hours post-dosing	From baseline to up to 6 hours post dose
Summary of participants with adverse events		From Day 1 to end of Follow-up Visit (approximately 4 weeks)

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: April 19, 2013
• First Submitted That Met QC Criteria: April 26, 2013
• First Posted (ESTIMATE): May 1, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): November 14, 2013
• Last Update Submitted That Met QC Criteria: November 13, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Phase 1; Pediatric Patients; persistent asthma; Albuterol Spiromax®; ProAir® HFA
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Albuterol; Procaterol
• Other Study ID Numbers: ABS-AS-102