Use of Buventol Easyhaler and Bufomix Easyhaler in Methacoline Challenge Testing (EASYRELIEF)

Use of Buventol Easyhaler and Bufomix Easyhaler as Relievers in Methacholine Challenge Testing and Inspiratory Flow Profiles During Induced Bronchoconstriction in Adult Subjects

The study compares Buventol® Easyhaler® and Bufomix® Easyhaler® to the current standard treatment during methacholine challenge test. The trial will also provide inspiratory flow profile data for Easyhaler inhaler.

This trial is designed to provide a further evidence for the use of Easyhaler in diagnostic bronchial challenge tests and on the use of Easyhaler inhaler during obstructive event.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Buventol® Easyhaler® 200 µg/inhalation dmDPI; Drug: Bufomix® Easyhaler® 160/4.5 µg/inhalation dmDPI; Drug: Ventoline® Evohaler® 100 µg/inhalation pMDI

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Hospital
  • Tampere, Finland, 33520
    • Tampere University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent (IC) obtained.
2. Finnish speaking adult (≥ 18 years old) subject indicated for methacholine challenge test.
3. The subject experiences FEV1 drop ≥ 20% compared to post-diluent spirometry.

Exclusion Criteria:

1. Subjects not eligible for methacholine challenge test for example for any of the following reasons:

   • Any respiratory infection within 2 weeks, or severe respiratory infection within 4 weeks before the study visit
   • FEV1 < 60% of predicted or < 1.0 l
   • Inability to perform acceptable and repeatable spirometry manoeuvres throughout the test procedure
   • Uncontrolled hypertension
   • Acute chest pain or unstable angina pectoris
   • Significant cardiac arrhythmias
   • Pneumothorax or recent bronchoscopy
   • Myocardial infarction or stroke in last 3 months
   • Known aortic aneurysm
   • Recent eye surgery or intracranial pressure elevation risk
   • Cholinesterase inhibitor medication
   • Pregnant or lactating females

2. Subjects who have used the following treatments before the study visit:

   • Short-acting β-agonists within 12 h
   • Long-acting β-agonists within 36 h
   • Ultra-long-acting β-agonists within 48 h
   • Long-acting anti-muscarinic agents within 168 h
   • Short-acting anticholinergics within 12 h
   • Oral theophylline within 24 h
   • Inhaled corticosteroids, leukotriene receptor antagonists and chromones within 4 weeks
3. Known hypersensitivity to the active substance(s) or the excipients of the study treatments (for example severe milk allergy, lactose contains small amounts of milk protein).
4. Administration of another investigational medicinal product within 30 days before the study visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buventol® Easyhaler® 200 µg/inhalation dmDPI; 400 μg of salbutamol from Buventol Easyhaler is administered as two inhalations.	Drug: Buventol® Easyhaler® 200 µg/inhalation dmDPI; Two doses will be administered; Other Names: Salbutamol 200 µg/dose dmDPI
Experimental: Bufomix® Easyhaler® 160/4.5 µg/inhalation dmDPI; 320 μg of budesonide and 9 μg of formoterol are administered from Bufomix Easyhaler as two inhalations.	Drug: Bufomix® Easyhaler® 160/4.5 µg/inhalation dmDPI; Two doses will be administered; Other Names: Budesonide/formoterol 160/4.5 µg/inhalation dmDPI
Active Comparator: Ventoline® Evohaler® 100 µg/inhalation pMDI; 400 μg of salbutamol from Ventoline Evohaler is administered via Volumatic spacer as four inhalations.	Drug: Ventoline® Evohaler® 100 µg/inhalation pMDI; Four doses will be administered via Volumatic spacer; Other Names: Salbutamol 100 µg/dose MDI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume in one second (FEV1)	Mean change in FEV1 from post-diluent to FEV1 after the first dose of reliever.	10 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects who recover from bronchoconstriction after first dose	Proportion of the subjects who recover to FEV1 > -10% compared to post-diluent FEV1 after first dose of reliever.	10 minutes
Forced expiratory volume in one second (FEV1)	Relative recovery of FEV1 after the study treatment dosing when compared to post-diluent FEV1.	10 minutes
Number of subjects who recover from bronchoconstriction after second dose	Proportions of subjects reaching FEV1 > -10% of post-diluent value after second dose of reliever.	20 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients needing medical attention	Proportion of subjects needing medical attention after study treatment	After study treatment administration until study completion (an average of 2.5 hours)
Inhalation profile via Easyhaler	Time-inspiratory flow -curve via Easyhaler measured with spirometer.	Before methacholine challenge and 10 minutes after the subject experiences FEV1 drop ≥ 20% compared to post-diluent spirometry

Collaborators and Investigators

• Sponsor: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Lauri Lehtimäki, Tampere University Hospital, Finland

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• 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; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Budesonide; Albuterol; Formoterol Fumarate
• Other Study ID Numbers: 0010032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No