Clinical study to test that the drug CHF 1535 100/6 (fixed combination of an anti-inflammatory drug and relaxing airways drug) delivered via pressurized inhaler using or not a spacer device is as effective in adolescent population as the licensed free combination of the same substances and compare it with administration in adults.

• Register: EUCTR
• Last refreshed on: 28 January 2013
• Main ID: EUCTR2011-005108-14-PL
• Date of registration: 20/12/2011
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: Clinical study to test that the drug CHF 1535 100/6 (fixed combination of an anti-inflammatory drug and relaxing airways drug) delivered via pressurized inhaler using or not a spacer device is as effective in adolescent population as the licensed free combination of the same substances and compare it with administration in adults.
• Scientific title: A single- dose, open label, randomized, 3-way crossover, clinical pharmacology study of CHF 1535 100/6 pMDI (fixed combination of beclomethazone dipropionate 100 µg plus formoterol fumarate 6 µg) with or without spacer device versus the free combination of licensed beclomethasone pMDI and formoterol pMDI in asthmatic adolescent patients and one open arm for adult patients as control group treated with CHF 1535 100/6 pMDI.
• Date of first enrolment: 28/01/2012
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005108-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Poland

Contacts

• Name: Chiesi Farmaceutici S.p.A.
• Affiliation: Chiesi Farmaceutici S.p.A.

• Name: Chiesi Farmaceutici S.p.A.
• Affiliation: Chiesi Farmaceutici S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female adolescents, aged = 12 and < 18 years or male and female adults, aged = 18
and = 65 years.
2. Written informed consent obtained by the patient in case of adult patients and by parents/legal
representative and by the minor (according to local regulation).
3. A diagnosis of asthma as defined in the GINA guidelines (updated 2010) 6 months before the
screening visit.
4. Male/female adolescent and adult patients with asthma stable enough, according to GINA
guidelines (updated 2010) and based on the Investigator’s opinion, to allow a wash out period
from inhaled BDP of 2 days before study each single day study treatments and any ICS other
than BDP of 1 day before each single day study treatments.
5. Male/female adolescents and adults asthmatic patients already treated with ICS or ICS/longacting
inhaled ß2-agonists or using short-acting inhaled ß2-agonists as reliever to control
asthma symptoms.
6. Adolescents and adults with a forced expiratory volume in one second (FEV1) > 70% of
predicted values (% pred) after withholding short acting ß2-agonist treatment for a minimum of
6 h prior to screening or 24 hours in case of long acting ß2-agonist.
7. Non- or ex-smokers who smoked less than 5 pack-years (e.g. < 20 cigarettes per day for 5 years)
and stopped smoking for at least 1 year.
8. A cooperative attitude and ability to be trained about the proper use of pMDI with and without
a spacer device and compliant to study procedures.
9. Body mass index (BMI) =18.5 and = 32 kg/m2
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant or breast-feeding female patients. Sexually active female not using efficient
contraception throughout the entire study period (e.g. oestro-progestatives, condoms,
intrauterine devices). A urinary pregnancy test will be performed at screening and treatment
visits (mandatory in the adult population and at discretion of the investigator in the adolescent
population) in women of childbearing potential;
2. Having received an investigational drug within 2 months before the screening visit (Visit 1)
3. Diagnosis of COPD, in the adult patients, as defined by the current GOLD guidelines (updated
2010).
4. Known hypersensitivity to the active treatments.
5. Inability to perform the required breathing technique and blood sampling.
6. Hospitalization due to exacerbation of asthma within 1 month prior to screening visit.
7. Lower respiratory tract infection within 1 month prior to screening visit;
8. Obesity, i.e. > 97% weight percentile by local standards.
9. Significant medical history of and/or treatments for cardiac, renal, neurological, hepatic,
endocrine diseases, that may interfere with patient’s safety, compliance, or study evaluations,
according to the Investigator’s opinion;
10. History of drug addiction or excessive use of alcohol (weekly intake in excess of 28 units
alcohol; one unit being a glass of beer, wine or a measure of spirits), or excessive consumption
of xanthine containing substances (daily intake in excess of 5 cups of coffee, tea, cola, etc) or
psychological or other emotional problems likely to invalidate informed consent, or limit the
ability of the subject to comply with the protocol requirements;
11. Treatment with a xanthine derivative (e.g. theophylline) formulations in the 4 weeks prior to
screening visit;
12. Blood donation (450 mL or more) (for the adult population) or significant blood loss in the 12
weeks before the screening visit.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Asthma
MedDRA version: 14.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: Foster®
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: BECLOMETASONE DIPROPIONATE
CAS Number: 5534-09-08
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
CAS Number: 43229-80-7
Other descriptive name: FORMOTEROL FUMARATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 6-

Trade Name: Atimos®
Pharmaceutical Form: Pressurised inhalation, solution
CAS Number: 43229-80-7
Other descriptive name: FORMOTEROL FUMARATE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 6-

Trade Name: Qvar®
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: BECLOMETASONE DIPROPIONATE
CAS Number: 5534/09/08
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To evaluate, in adolescents, the systemic exposure to B17MP (active metabolite of BDP) as
AUC0-t, after inhalation of CHF 1535 100/6 pMDI with and without spacer device (AeroChamber
Plus™) in comparison with the already licensed free combination of BDP pMDI and formoterol
pMDI without spacer.

Timepoint(s) of evaluation of this end point: The area under the plasma concentration vs. time curve observed from time 0 up to the last
measurable concentration will be computed using the linear trapezoidal rule [13]. An 8 hour value is required for derivation of AUC0-t.
Nine (9) blood samples of approximately 1 mL for the determination of BDP and its metabolite B17MP in plasma will be collected in the 0-8 h interval after dosing [pre-dose (within 5 minutes from dosing), 5 min, 15 min, 30 min, 1, 2, 4, 6, 8 hours post dose].

Primary end point(s): Plasma AUC0-t for B17MP

Secondary Objective: - To evaluate the pharmacokinetic profile of BDP and formoterol and additional PK
properties of B17MP after inhalation of CHF 1535 100/6 pMDI both with and without
spacer in comparison with a free combination of licensed BDP and Formoterol pMDIs.
- To evaluate the systemic effects in terms of heart rate and circulating potassium and glucose
levels and also the general safety and tolerability profile of BDP/B17MP and formoterol of
CHF 1535 100/6 pMDI fixed combination both with and without spacer.
- To evaluate, in adolescents, the effects of the spacer device (AeroChamber Plus™) on the
systemic exposure to BDP/B17MP and formoterol after inhalation of the fixed combination.
- To evaluate the systemic exposure to BDP/B17MP and formoterol after inhalation of CHF
1535 pMDI in adolescents in comparison to adults without the spacer device.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: PK - BDP/B17Mp/Formoterol in plasma at pre-dose, 5 min, 15 min, 30 min, 1, 2, 4, 6, 8 hours post dose
PD - Potassium and Glucose at pre-dose, 30 min, 1, 2, 4, 6, 8 hours post dose;
Safety - Heart rate will be measured at pre-dose, 5 min, 10 min, 15 min, 30 min, 1, 2, 4, 6, 8 hours post dose
Efficacy - Lung function measurements (FEV1) at pre-dose, 30 min, 1, 2, 4, 6, 8 hours post dose

Secondary end point(s): Pharmacokinetics:
- Plasma BDP and formoterol AUC0-t, AUC0-inf , Cmax, tmax and t½
- Plasma B17MP AUC0-0.5h, AUC0-inf, Cmax, tmax and t½
Pharmacodynamics:
- Plasma Potassium Cmin, tmin and AUC0-t
- Plasma Glucose Cmax, tmax, AUC0-2h and AUC0-t
Efficacy:
- Peak FEV1, FEV1 time averaged value (FEV1 AUC0-8h/8h)
Safety:
- Heart Rate: Time averaged value (calculated as AUC0-8h/8h).
- General tolerability of the treatments, adverse events and adverse drug reactions.

Secondary ID(s)

CCD-1104-PR-0062

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.