A Study Comparing the Pharmacokinetic, Pharmacodynamic and Safety of CHF 1535 (Fixed Combination of Beclomethasone + Formoterol) Administered Via the NEXT DPI, Versus the Free Combination of Licenced Beclomethasone DPI and Formoterol DPI in Asthmatic Adolescent and Adult Patients. (ADONE)

A Multicenter, Multinational, Single-Dose, Open Label, Randomized, 2-Way Crossover, Clinical Pharmacology Study of CHF 1535 100/6 Next™ DPI (Fixed Combination of Beclomethasone Dipropionate 100 µg Plus Formoterol 6 µg) Versus the Free Combination of Licensed Beclomethasone DPI and Formoterol DPI in Asthmatic Adolescents and Adult Patients

The purpose of this study is to demonstrate that the CHF 1535 (fixed combination of Beclometasone Dipropionate (BDP) 100 µg / Formoterol Fumarate (FF) 6 µg) delivered via the NEXT Dry Powder Inhaler (DPI) does not show a greater exposure to BDP, Beclometasone-17-Monopropionate(B17MP, active metabolite of BDP) and FF in comparison to a free combination of BDP DPI plus FF DPI licensed products after a morning dose administration of BDP and FF (total dose of BDP 400 µg / FF 24 µg) in adolescent and adult asthmatic patients.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: CHF1535 NEXT DPI; Drug: BDP DPI and formoterol DPI

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2800
    • Copenhagen University Hospital
• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
    • Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Male and female adolescents (≥ 12 years old) and adults (≥18 and ≤ 65 years old)
2. Written informed consent;
3. Diagnosis of asthma as defined in the GINA guidelines;
4. Patients with stable asthma, according to the Investigator's opinion;
5. Asthmatic patients already treated with ICS or using short-acting inhaled β2-agonists as reliever to control asthma symptoms;
6. Patients with a forced expiratory volume in one second (FEV1) > 70% of predicted values;
7. Patients with a peak inspiratory flow (PIF) > 40 L/min
8. Reversibility test;
9. Non- or ex-smokers;
10. A cooperative attitude and ability to be trained about the proper use of DPI and compliant to study procedures;

Main Exclusion Criteria:

1. Pregnant or lactating female;
2. Having received an investigational drug within 2 months before the screening visit
3. Diagnosis of COPD as defined by the current GOLD guidelines;
4. Significant medical history of and/or treatments for cardiac, renal, neurological, hepatic, endocrine diseases, or any laboratory abnormality;
5. Known hypersensitivity to the active treatments;
6. History of drug addiction or excessive use of alcohol;
7. Treatment with a xanthine derivative (e.g. theophylline) formulation in the 4 weeks prior to screening;
8. Hospitalization due to asthma exacerbation or asthma exacerbation within 1 month prior to the screening visit;
9. Inability to perform the required breathing technique and blood sampling;
10. Lower respiratory tract infection within 1 month prior to the screening visit;
11. Blood donation (450 mL or more) or significant blood loss in the 12 weeks before the screening visit.

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: CHF1535 NEXT DPI; Male and female adolescents and adult patients (≥ 12 years old) treated with CHF1535 NEXT DPI	Drug: CHF1535 NEXT DPI; FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE 100µg PLUS FORMOTEROL FUMARATE 6 µg DRY POWDER INHALER
ACTIVE_COMPARATOR: Free combination BDP and FF; Male and female adolescents and adult patients (≥ 12 years old) treated with a free combination of licenced BDP and FF	Drug: BDP DPI and formoterol DPI; FREE COMBINATION OF LICENSED BECLOMETHASONE DPI AND FORMOTEROL DPI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic exposure to B17MP (active metabolite of BDP) after single dose (4 inhalations) of CHF1535 100/6 NEXT DPI in comparison with an already approved free combination of BDP DPI and FF DPI	Plasma AUC0-t for B17MP	0-8hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events		during the whole study period
Different pharmacokinetic parameters	BDP/B17MP and FF PK parameters	0-8hrs
Lung function parameters	Peak FEV1, FEV1 time averaged value (FEV1 AUC0-t/8).	0-8hrs
Plasma potassium	Plasma Potassium Cmin, tmin and AUC0-t	0-8hrs
Plasma glucose	Plasma Glucose Cmax, tmax, AUC0-2h and AUC0-t	0-8hrs
Heart rate	time averaged value (AUC0-t/8)	0-8hrs

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Study Director: Dave Singh, MD, Medicines Evaluation Unit; Study Director: Hans Bisgaard, MD, Copenhagen University Hospital at Herlev

Publications and helpful links

General Publications

• Govoni M, Piccinno A, Lucci G, Poli G, Acerbi D, Baronio R, Singh D, Kuna P, Chawes BL, Bisgaard H. The systemic exposure to inhaled beclometasone/formoterol pMDI with valved holding chamber is independent of age and body size. Pulm Pharmacol Ther. 2015 Feb;30:102-9. doi: 10.1016/j.pupt.2014.04.003. Epub 2014 Apr 16.
• Chawes BL, Govoni M, Piccinno A, Kreiner-Moller E, Vissing NH, Mortensen L, Nilsson E, Bisgaard A, Deleuran M, Skytt N, Samandari N, Acerbi D, Bisgaard H. A clinical pharmacology study of fixed vs. free combination of inhaled beclometasone dipropionate and formoterol fumarate dry powder inhalers in asthmatic adolescents. Br J Clin Pharmacol. 2014 Nov;78(5):1169-71. doi: 10.1111/bcp.12424. No abstract available.

Helpful Links

• Study Record on EU Clinical Trials Register including results

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: August 27, 2010
• First Submitted That Met QC Criteria: August 27, 2010
• First Posted (ESTIMATE): August 30, 2010

Study Record Updates

• Last Update Posted (ACTUAL): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Adolescents; Asthma; Adults; PK
• 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; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate
• Other Study ID Numbers: CCD-1017-PR-0034; 2010-018947-33 (EUDRACT_NUMBER)