A Study in Asthmatic Children (6 to <12 Yrs) Comparing Single Doses of Formoterol and Foradil® Evaluating Efficacy (CHASE 2)

A Phase 2, Randomized, Blinded, 5-period Cross-over, Placebo and Active Controlled, Multicenter, Dose-finding Study Comparing Single Doses of Formoterol 2.25 µg, 4.5 µg, and 9 µg Delivered Via Symbicort pMDI and Foradil® 12 µg Evaluating the Relative Bronchodilating Effects and Safety in Children

This purpose of the study is to investigate the bronchodilating effects of 3 different dosages of formoterol given in combination with budesonide as Symbicort pMDI.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: 80/2.25 μg Symbicort pMDI; Drug: 40 μg budesonide HFA pMDI; Drug: placebo HFA pMDI; Drug: 80/4.5 μg Symbicort pMDI; Drug: Foradil Aerolizer 12 μg

Detailed Description

A Phase 2, randomized, blinded, 5-period cross-over, placebo and active controlled, multicenter, dose-finding study comparing single doses of formoterol 2.25 µg, 4.5 µg, and 9 µg delivered via Symbicort pMDI and Foradil® 12 µg evaluating the relative bronchodilating effects and safety in children.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Dublin, Bulgaria
    • Research Site
• Czech Republic
  • Dublin, Czech Republic
    • Research Site
• Hungary
  • Budapest, Hungary
    • Research Site
  • Dublin, Hungary
    • Research Site
  • Miskolc, Hungary
    • Research Site
  • Sopron, Hungary
    • Research Site
• Poland
  • Dublin, Poland
    • Research Site
• South Africa
  • Cape Town, South Africa
    • Research Site
  • Dublin, South Africa
    • Research Site
  • Gauteng
    • Krugersdorp, Gauteng, South Africa
      • Research Site
  • Kwa Zulu Natal
    • Pietermariztburg, Kwa Zulu Natal, South Africa
      • Research Site
  • Kz-natal
    • Durban, Kz-natal, South Africa
      • Research Site
  • W Cape
    • Cape Town, W Cape, South Africa
      • Research Site
    • Claremont, W Cape, South Africa
      • Research Site
• United States
  • California
    • Huntington, California, United States
      • Research Site
    • Long Beach, California, United States
      • Research Site
    • Mission Viejo, California, United States
      • Research Site
    • Orange, California, United States
      • Research Site
    • Rolling Hills Estate, California, United States
      • Research Site
  • Florida
    • Sarasota, Florida, United States
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States
      • Research Site
  • North Carolina
    • Morrisville, North Carolina, United States
      • Research Site
    • Raleigh, North Carolina, United States
      • Research Site
  • Oregon
    • Eugene, Oregon, United States
      • Research Site
    • Lake Oswego, Oregon, United States
      • Research Site
    • Medford, Oregon, United States
      • Research Site
    • Portland, Oregon, United States
      • Research Site
  • Pennsylvania
    • Altoona, Pennsylvania, United States
      • Research Site
    • Upland, Pennsylvania, United States
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States
      • Research Site
  • Texas
    • El Paso, Texas, United States
      • Research Site
    • San Antonio, Texas, United States
      • Research Site
    • Waco, Texas, United States
      • Research Site
  • Virginia
    • Springfield, Virginia, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has a documented clinical diagnosis of asthma for at least 6 months prior to Visit 1
• Has a FEV1 measured at least 6 hours after the last dose of inhaled, short-acting β2-agonist (SABA) and at least 48 hours after the last dose of inhaled long-acting β2-agonist of =60% and =85% of predicted normal.
• Demonstrated reversibility of FEV1 of =15% from pre short acting beta agonist level within 15 to 30 minutes after administration of a standard dose of short acting beta agonist

Exclusion Criteria:

• Has been hospitalized for >24 hours at least once or required emergency treatment or urgent care visit more than once for an asthma-related condition during the 6 months prior to Visit 1
• Has required treatment with systemic corticosteroids (eg, oral, parenteral, or rectal) for any reason within the 12 weeks prior to Visit 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BUD 160/FM 2.25; 2.25 μg formoterol (as 80/2.25 μg Symbicort pMDI × 1 inhalation) + 40 μg budesonide HFA pMDI × 2 inhalations	Drug: 80/2.25 μg Symbicort pMDI; inhalation; Drug: 40 μg budesonide HFA pMDI; inhalation
EXPERIMENTAL: BUD 160/FM 4.5; placebo HFA pMDI × 1 inhalation + 4.5 μg formoterol (as 80/2.25 μg Symbicort pMDI × 2 inhalations)	Drug: 80/2.25 μg Symbicort pMDI; inhalation; Drug: placebo HFA pMDI; inhalation
EXPERIMENTAL: BUD 160/FM 9.0; placebo HFA pMDI × 1 inhalation + 9 μg formoterol (as 80/4.5 μg Symbicort pMDI × 2 inhalations)	Drug: placebo HFA pMDI; inhalation; Drug: 80/4.5 μg Symbicort pMDI; inhalation
PLACEBO_COMPARATOR: BUD 160; placebo HFA pMDI × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations	Drug: 40 μg budesonide HFA pMDI; inhalation; Drug: placebo HFA pMDI; inhalation
ACTIVE_COMPARATOR: BUD 160/Foradil 12.0; Foradil Aerolizer 12 μg × 1 inhalation + 80 μg budesonide HFA pMDI × 2 inhalations	Drug: 40 μg budesonide HFA pMDI; inhalation; Drug: Foradil Aerolizer 12 μg; inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average 12 Hour Forced Expiratory Volume in 1 Second (FEV1)	Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 was obtained from the full expiratory flow-volume-time curve. FEV1 was measured at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes post administration of randomized study medication. Twelve-hour serial FEV1 was calculated through an AUC determination and then divided by time, so that the final value is expressed in liters. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0.	at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 at 12 Hours After Study Medication Inhalation	Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. The FEV1 value at 12 hours after dosing was taken as the 12-hour measurement (720 minutes) from the serial spirometry. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0.	12 hours after dosing
Maximal FEV1 During the 12-hour Study Period	Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 was measured at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes post administration of randomized study medication. The maximum FEV1 value was defined as the largest observed FEV1 value recorded during each 12-hour serial spirometry procedure. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0.	at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose
Urinary Excretion of Formoterol During the 12 Hours Following Inhalation of Study Drug	The amount of formoterol excreted unchanged in urine over the 12-hour period after administration [Ae(0-12h)] was calculated from the concentration of formoterol in urine multiplied by the total volume of urine collected. Volume was determined from the weight of the collected urine times an assumed urine density of 1020 g/L. The data for six patients who did not have measurable formoterol in their urine on the Foradil 12 μg treatment day was excluded from the analysis. All other urine concentrations below the lower limit of quantification were set to zero. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0.	0 to 12 hours

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Lars-Goran Carlsson, MD, AstraZeneca

Publications and helpful links

General Publications

• Berger WE, Gillen M, Eckerwall G, Uryniak T, Trudo FJ, Lampl KL. Bronchodilator effect of single-dose formoterol administered by pressurized metered-dose inhaler in children with asthma aged 6 to <12 years receiving budesonide. Allergy Asthma Proc. 2014 Mar-Apr;35(2):134-40. doi: 10.2500/aap.2014.35.3746.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: June 1, 2010
• First Submitted That Met QC Criteria: June 2, 2010
• First Posted (ESTIMATE): June 3, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): October 31, 2013
• Last Update Submitted That Met QC Criteria: October 30, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Foradil; Symbicort; asthmatic children
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination
• Other Study ID Numbers: D589GC00002