Clinical trial NCT02787967: Clinical Pharmacology of 35/4 NEXThaler® in Children 5-11 Years Old
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2016-06-02
Enrollment: 26
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Plasma Area Under Curve (AUC0-t) for B17MP, active metabolite of BDP
timeFrame: predose, 15,30min, 1,2,4,6,8 hours post dose
Secondary outcomes:
measure: B17MP Cmax
timeFrame: predose, 15min,30min,1,2,4,6,8 hours post dose
measure: BDP Area Under Curve (AUC)
timeFrame: predose, 15min,30min,1,2,4,6,8 hours post dose
measure: Formoterol Area Under Curve (AUC), Cmax, Tmax, T1/2 [
timeFrame: predose, 15min, 30 min, 1,2,4,6,8 hours postdose
measure: Formoterol Cmax
timeFrame: predose, 15min, 30 min, 1,2,4,6,8 hours postdose
measure: Formoterol Tmax
timeFrame: predose, 15min, 30 min, 1,2,4,6,8 hours postdose
measure: Formoterol T1/2
timeFrame: predose, 15min, 30 min, 1,2,4,6,8 hours postdose
measure: plasma potassium Area Under Curve (AUC)
timeFrame: predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose
measure: plasma potassium Cmin
timeFrame: predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose
measure: plasma potassium Tmin
timeFrame: predose, 15min, 30min, 1, 2, 4, 6, 8 hours postdose
measure: Urinary Cortisol: Amount excreted in 0-8hours (Ae),8h cortisol urinary excretion normalized for 8h creatinine excretion (Ae/Aecreat).
timeFrame: from predose up to 8 hours postdose
measure: B17MP Tmax
timeFrame: predose, 15min,30min,1,2,4,6,8 hours post dose
measure: B17MP T1/2
timeFrame: predose, 15min,30min,1,2,4,6,8 hours post dose
measure: BDP Cmax
timeFrame: predose, 15min,30min,1,2,4,6,8 hours post dose
measure: BDP Tmax
timeFrame: predose, 15min,30min,1,2,4,6,8 hours post dose
measure: BDP T1/2
timeFrame: predose, 15min,30min,1,2,4,6,8 hours post dose
Other outcomes:
Locations:
city: Copenaghen
country: Denmark
facility: BørneAstmaKlinikken, Hans Knudsens Plads 1A,
Study officials:
affiliation: Copenhagen Studies on Asthma in Childhood
name: Hans Bisgaard, MD
role: PRINCIPAL_INVESTIGATOR
References: