A Single-dose, Open-label, Randomized, 2-way Cross-over Study of CHF 1535 35/4 NEXThaler® (Fixed Combination of Beclometasone Dipropionate (BDP) 35 μg Plus Formoterol Fumarate (FF) 4 μg Versus the Free Combination of Licensed BDP DPI (Dry Powder Inhaler) and FF DPI in Asthmatic Children

Clinical Pharmacology of 35/4 NEXThaler® in Children 5-11 Years Old

Sponsors

Lead sponsor: Chiesi Farmaceutici S.p.A.

Source Chiesi Farmaceutici S.p.A.
Brief Summary

The study will be conducted in asthmatic children aged 5 to 11 years and is based on a single-dose, open-label, randomized, 2-way cross-over design where a Dry Powder Inhaler (DPI) fixed combination of beclometasone dipropionate (BDP) 35 μg plus formoterol fumarate (FF) 4 μg is compared with the free combination of licensed BDP DPI and FF DPI

Detailed Description

This is a pharmacokinetic comparison of NEXThaler 35/4 μg versus the free combination of Beclomethasone DPI and Formoterol DPI in children (5 to 11 years old) of a formulation already approved in adults.

Overall Status Completed
Start Date August 2016
Completion Date June 2017
Primary Completion Date June 2017
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Plasma Area Under Curve (AUC0-t) for B17MP, active metabolite of BDP predose, 15,30min, 1,2,4,6,8 hours post dose
Secondary Outcome
Measure Time Frame
B17MP Cmax predose, 15min,30min,1,2,4,6,8 hours post dose
BDP Area Under Curve (AUC) predose, 15min,30min,1,2,4,6,8 hours post dose
Formoterol Area Under Curve (AUC), Cmax, Tmax, T1/2 [ predose, 15min, 30 min, 1,2,4,6,8 hours postdose
Formoterol Cmax predose, 15min, 30 min, 1,2,4,6,8 hours postdose
Formoterol Tmax predose, 15min, 30 min, 1,2,4,6,8 hours postdose
Formoterol T1/2 predose, 15min, 30 min, 1,2,4,6,8 hours postdose
plasma potassium Area Under Curve (AUC) predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose
plasma potassium Cmin predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose
plasma potassium Tmin predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose
Urinary Cortisol: Amount excreted in 0-8hours (Ae),8h cortisol urinary excretion normalized for 8h creatinine excretion (Ae/Aecreat). from predose up to 8 hours postdose
B17MP Tmax predose, 15min,30min,1,2,4,6,8 hours post dose
B17MP T1/2 predose, 15min,30min,1,2,4,6,8 hours post dose
BDP Cmax predose, 15min,30min,1,2,4,6,8 hours post dose
BDP Tmax predose, 15min,30min,1,2,4,6,8 hours post dose
BDP T1/2 predose, 15min,30min,1,2,4,6,8 hours post dose
Enrollment 26
Condition
Intervention

Intervention type: Drug

Intervention name: CHF 1535 35/4µg NEXThaler®

Description: 4 (four) inhalations (total dose: BDP/FF 140/16 µg)

Arm group label: NEXThaler® 35/4µg

Intervention type: Drug

Intervention name: free comb. beclomethasone DPI and formoterol DPI

Description: 2 (two) inhalations BDP 100 µg DPI + 4 (four) inhalations FF 6 µg DPI (total dose: BDP 200 µg + FF 24 µg

Arm group label: Reference treatment

Eligibility

Criteria:

Inclusion Criteria:

- Male/female children with asthma stable enough, according to paediatrician opinion, to allow a wash out period from steroids of 3 days before study treatments.

- Male/female children with asthma on regular treatment with ICS or using short-acting inhaled 2-agonist as reliever to control asthma symptoms.

- Age ≥ 5 < 12 years (8 to 10 children in the age range 5-8 years old).

- Children with a forced expiratory volume in one second (FEV1)>70% of predicted values (% pred) after withholding 2-agonists treatment for a minimum of 4 h prior to screening and to each study treatment.

- A cooperative attitude and ability to be trained about the proper use of DPI, ability to use correctly the medical devices and compliant to study procedures

Exclusion Criteria:

- Past or present diagnosis of cardiovascular, renal or liver disease.

- Known hypersensitivity to the active treatmen

- Exacerbation of asthma symptoms within 4 weeks prior to screening.

- Inability to perform the required breathing technique and blood sampling.

- Hospitalization due to exacerbation of asthma within 1 month prior to screening (Visit 1).

- Lower respiratory tract infection within 1 month prior to screening (Visit 1).

- Disease (other than asthma) which might influence the outcome of the study.

- Obesity, i.e. > 97% weight percentile by local standards

Gender: All

Minimum age: 5 Years

Maximum age: 11 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Hans Bisgaard, MD Principal Investigator Copenhagen Studies on Asthma in Childhood
Location
facility BørneAstmaKlinikken, Hans Knudsens Plads 1A,
Location Countries

Denmark

Verification Date

February 2018

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Number Of Arms 2
Arm Group

Arm group label: NEXThaler® 35/4µg

Arm group type: Experimental

Description: CHF 1535 35/4µg NEXThaler® Dry Powder Inhaler, 4 inhalations. Total Dose: BDP 200µg FF 16µg

Arm group label: Reference treatment

Arm group type: Active Comparator

Description: Drug: free comb. beclomethasone DPI and formoterol DPI 2 (two) inhalations BDP 100 µg DPI + 4 (four) inhalations FF 6 µg DPI (total dose: BDP 200 µg + FF 24 µg

Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov