Clinical Pharmacology of CHF 1535 50/6 ug Next DPI in Children 5-11 Years Old (PAED4)

A Single-dose,Open-label,Randomized,2-way Cross-over,Clinical Pharmacology Study of CHF1535 50/6 NEXT DPI® Fixed Combination of Beclomethasone Dipropionate 50µg Plus Formoterol Fumarate 6µg)Versus the Free Combination of Licensed Beclomethasone DPI and Formoterol DPI in Asthmatic Children

This is a pharmacokinetic comparison of CHF 1535 50/6 NEXT DPI versus the free combination of Beclomethasone DPI and Formoterol DPI in children (5 to 11 years old) of a formulation already approved in adults.

Study Overview

• Status: Completed
• Conditions: Asthma in Children
• Intervention / Treatment: Drug: free comb. beclomethasone DPI and formoterol DPI; Drug: CHF 1535 50/6 NEXT DPI

Detailed Description

Pharmacokinetic study in asthmatic children 5 to 11 years old treated with either a fixed combination of beclomethasone 50 ug/unit dose plus formoterol fumarate 6 ug/unit dose via the NEXT DPI dry powder inhaler or a free combination of Beclomethasone 100 ug DPI and Formoterol 6 ug DPI according to a cross-over design.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen,, Denmark, 2100
    • BørneAstmaKlinikken, Hans Knudsens Plads 1A,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male/Female children aged 5 -11y
2. Written informed consent obtained by parents/legal representative (according to local regulation) and by the minor (age and local regulation permitting).
3. Children with stable asthma
4. Children with asthma on regular treatment with ICS or using short-acting inhaled beta2-agonists as reliever to control asthma symptoms
5. Forced expiratory volume in one second (FEV1) > 70% of predicted values (% pred) after withholding beta2-agonists treatment for a minimum of 4 h prior to each study treatment.
6. A cooperative attitude and ability to be trained about the proper use of DPI and compliant to study procedures.

Exclusion Criteria:

1. Past or present diagnoses of cardiovascular, renal or liver disease
2. Known hypersensitivity to the active treatments
3. Exacerbation of asthma symptoms within the previous 4 weeks
4. Inability to perform the required breathing technique and blood sampling
5. Hospitalization due to exacerbation of asthma within 1 month prior to screening (visit 1)
6. Lower respiratory tract infection within 1 month prior to screening (visit 1)
7. Disease (other than asthma) which might influence the outcome of the study
8. Obesity, i.e. > 97% weight percentile by local standards

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: reference treatment; Free combination of Beclomethasone dipropionate DPI and Formoterol fumarate DPI	Drug: free comb. beclomethasone DPI and formoterol DPI; free combination of beclomethasone dipropionate 100 ug/unit DPI (two inhalations, total dose 200 ug), and formoterol fumarate 6 ug/unit DPI (four inhalations, total dose 24 ug).
Experimental: CHF 1535 NEXT DPI; CHF 1535 50/6 NEXT DPI	Drug: CHF 1535 50/6 NEXT DPI; four inhalations of CHF 1535 50/6 NEXT DPI, a fixed combination of beclomethasone dipropionate 50 ug plus formoterol fumarate 6 ug (TOTAL DOSE:BDP/FF 200/24 ug)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B17MP (active metabolite of BDP) Area Under Curve (AUC)	B17MP: Profile of Pharmacokinetics	predose, 15,30min, 1,2,4,6,8 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary Cortisol: Amount excreted in 0-8hours (Ae),8h cortisol urinary excretion normalized for 8h creatinine excretion (Ae/Aecreat).	Urinary cortisol to evaluate drug systemic effect	from predose up to 8 hours postdose
B17MP Cmax,Tmax,T1/2	BDP: profile of pharmacokinetics.	predose, 15min,30min,1,2,4,6,8 hours post dose
BDP Area Under Curve (AUC), Cmax, Tmax, T1/2	BDP: profile of Pharmacokinetics	predose, 15min,30min,1,2,4,6,8 hours postdose
Formoterol Area Under Curve (AUC), Cmax, Tmax, T1/2	Formoterol: profile of pharmacokinetics	predose, 15min, 30 min, 1,2,4,6,8 hours postdose
plasma potassium Area Under Curve (AUC), Cmin, Tmin	plasma potassium to evaluate drug systemic effect	predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose
Heart Rate: Time averaged Heart Rate value: AUC0-t/t	Heart Rate to evaluate drug systemic effect	predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Hans Bisgaard, BorneAstmaKlinikken, Copenaghen, Denmark

Publications and helpful links

General Publications

• Chawes BL, Govoni M, Kreiner-Moller E, Vissing NH, Poorisrisak P, Mortensen L, Nilsson E, Bisgaard A, Dossing A, Deleuran M, Skytt NL, Samandari N, Piccinno A, Sergio F, Ciurlia G, Poli G, Acerbi D, Singh D, Bisgaard H. Systemic exposure to inhaled beclometasone/formoterol DPI is age and body size dependent. Respir Med. 2014 Aug;108(8):1108-16. doi: 10.1016/j.rmed.2014.05.007. Epub 2014 Jun 17.

Helpful Links

• Study Record on EU Clinical Trials Register including results

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: October 28, 2011
• First Submitted That Met QC Criteria: November 7, 2011
• First Posted (Estimate): November 9, 2011

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: asthma children NEXT DPI LABA ICS inhalation
• 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; 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; Beclomethasone; Formoterol Fumarate
• Other Study ID Numbers: CCD-1103-PR-0058