Single blind, randomized, crossover, repeated dose, pharmacokinetic and pharmacodynamic interaction study of CHF 4226 HFA and Extra-fine BUD HFA in asthmatic patients

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2006-002094-46-BE
• Date of registration: 15/06/2006
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: Single blind, randomized, crossover, repeated dose, pharmacokinetic and pharmacodynamic interaction study of CHF 4226 HFA and Extra-fine BUD HFA in asthmatic patients
• Scientific title: Single blind, randomized, crossover, repeated dose, pharmacokinetic and pharmacodynamic interaction study of CHF 4226 HFA and Extra-fine BUD HFA in asthmatic patients
• Date of first enrolment: 26/06/2006
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002094-46
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with mild or moderate asthma and a FEV1= 70% predicted stabilized on inhaled corticosteroids or combination of inhaled steroids and long acting beta2 agonists.
2. Written informed consent obtained.
3. Male or female patients aged = 18 years and =70.
4. Patients with a documented positive response to the reversibility test (i.e. FEV1 increase = 15% and 200mL from baseline value after 2 puffs of 100 mg of inhaled salbutamol pMDI) within the 12 months preceding the screening visit or performed at screening visit after a wash-out of 2 days for patient asthma treatment (inhaled corticosteroids or combination of inhaled steroids and long acting beta2 agonists) or a documented positive response to the methacholine challenge test.
5. Non-smokers or ex-smokers <5 pack-year [e.g. less than 1 pack cigarettes (i.e. 20 cigarettes) per day for 5 years or 2 packs cigarettes per day for 2.5 years] and having stopped smoking >1 year.
6. Patients with a co-operative attitude and ability to be trained to correctly use the pMDI.
7. Patients with no clinically relevant abnormalities in physical examination, vital signs measurements and ECG

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant or lactating females or females at risk of pregnancy, i.e. those not making use of an effective contraceptive method.
2. Patients not able to carry out pulmonary function testing.
3. Diagnosis of COPD as defined by the current GOLD guidelines.
4. History of near fatal asthma.
5. History of significant seasonal variation of asthma.
6. Hospitalization due to asthma in the 8 weeks prior screening.
7. Patients with asthma exacerbation (see definition in Appendix 8) within the 4 weeks prior to screening visit.
8. Patients with more than 3 episodes of asthma exacerbation (see definition in Appendix 8) within the 6 months prior to screening visit.
9. Patients with an uncontrolled cardiovascular (e.g., uncontrolled hypertension), respiratory, hematologic, immunologic, renal, neurologic, hepatic, endocrine (e.g., uncontrolled diabetes mellitus) or other disease, or any condition that might, in the judgment of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.
10. Patients with a history of coronary artery disease, cerebrovascular disease, or cardiac arrhythmias.
11. Patients with a laboratory value (i.e. hematology, blood chemistry, urinalysis, ECG) indicating an uncontrolled concomitant disease.
12. Patients with a serum potassium value = 3.5 mEq/L or >5.5mEq/L and/or a fasting serum glucose value = 140 mg/dL.
13. Patients treated with any non-permitted concomitant medication (see list in 5.13).
14. Patients with a QTc interval (Bazett’s formula) at the screening visit ECG test >450 msec.
15. Cancer or any other chronic disease with poor prognosis and /or affecting patient status.
16. History or presence of drug addiction (positive drug screen) or excessive use of alcohol (weekly intake in excess of 28 units alcohol; one unit alcohol equals a glass of beer, a glass of 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 that are likely to invalidate informed consent, or limit the ability of the patient to comply with the protocol requirements
17. Allergy, sensitivity or intolerance to beta2-aderenergic agonists and/or budesonide and/or study drug formulation ingredients.
18. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study.
19. Patients who received any investigational new drug within the last 8 weeks prior to the screening visit.
20. Blood donation (450 mL or more) or significant blood loss less than 12 weeks before the first intake of study drug.
21. Positive HIV1 or HIV2 serology.
22. Hepatitis serology positive for acute or chronic hepatitis B or hepatitis C.
23. Unsuitable veins for repeated puncture.



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

Health Condition(s) or Problem(s) studied

Asthmatics patients

Intervention(s)

Product Name: CARMOTEROL
Product Code: CHF 4226 - HFA
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: carmoterol hydrochloride
Current Sponsor code: CHF 4226.01
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Pressurised inhalation, solution
Route of administration of the placebo: Inhalation use

Product Name: BUDESONIDE
Product Code: CHF 1536-EF HFA
Pharmaceutical Form: Pressurised inhalation, solution
INN or Proposed INN: BUDESONIDE
Current Sponsor code: CHF 1536-EF HFA
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Pressurised inhalation, solution
Route of administration of the placebo: Inhalation use

Pharmaceutical Form: Tablet
INN or Proposed INN: Montelukast sodium
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Formoterol
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 12-

Pharmaceutical Form: Pressurised inhalation, suspension
INN or Proposed INN: Salbutamol sulphate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: - To compare the effects on lung function of the free combination of CHF 4226 HFA and extra-fine BUD HFA in comparison with CHF 4226 HFA and extra-fine BUD HFA administered as single agent. - Safety and tolerability will be evaluated by monitoring adverse events and adverse drug reactions, cardiovascular parameters (QTc, heart rate, blood pressure), by measuring cortisol and potassium serum profiles, and cortisol urinary excretion.- To evaluate the effect of the combination CHF 4226 HFA and extra-fine BUD HFA with high resolution/multislice CT scans imaging technique in two subgroups of patients.

Main Objective: - To compare the systemic exposure of the free combination of CHF 4226 HFA and extra-fine BUD HFA pMDI administered once daily for 4 consecutive weeks in comparison with CHF 4226 HFA and extra-fine BUD HFA administered as single agent.

Primary end point(s): Concentration-time profiles of Budesonide epimers in plasma and of CHF 4226 in urine, and derived pharmacokinetic parameters the last day of treatment in each study period. The primary parameters will be AUC(0-24h), AUC(0-¥), Cmax, tmax as metrics of extent and rate of absorption for Budesonide, and Ae0-24 for CHF 4226.

Secondary ID(s)

FB/PS/14/160/06