Clinical trial NCT02227394: Study to Compare the Effects of Z7200 And Symbicort® Turbohaler on Respiratory Imaging Parameters in Asthmatic Patients
Official title: A Double Blind, Double Dummy, Randomized, Two Way Cross-over Study to Compare the Effects of Z7200 and Symbicort® Turbohaler on Functional Respiratory Imaging Parameters in Asthmatic Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Asthma Chronic
Asthma Bronchial
Asthmatic
Keywords: Asthma
Functional Respiratory Imaging
Computational Fluid Dynamic
Lead sponsor: Zambon SpA
Sponsor class: INDUSTRY
Collaborators: name: FLUIDDA nv
First posted: 2014-08-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Primary objective:

The primary objective of this study is to evaluate the effect of the products under investigation on functional respiratory imaging parameters and evaluate the particle deposition with Computational fluid dynamics (CFD).

Secondary Objectives:

The secondary objectives of this study were to assess the effect of test product and reference product on:

* lung function (spirometry and body plethysmography),
* exercise capacity (6-Minute Walking Test \[6MWT\] or equivalent method to measure exercise tolerance),
* dyspnea (Borg Category \[C\] Ratio \[R\] 10 \[Borg CR10\] scale and Visual Analogue Scale \[VAS\] dyspnea).

Furthermore, the safety of the test product and reference product was evaluated through monitoring of AEs throughout the study.

Detailed description: This study is conducted as a randomized, double blind, double dummy two-period crossover study in stable asthma patients treated in accordance with the Global Initiative for Asthma (GINA) guidelines.

On the first dosing day (Period 1, Visit 2), asthma stability was assessed based on review of pharmacologic treatment monitoring and FEV1 change from the previous visit. Patients were then randomized and allocated to one of two treatment sequences (i.e. test/reference or reference/test). Randomization codes were assigned strictly sequentially as patients became eligible for randomization. Patients received a single dose consisting of two inhalations of either the test product or the reference product, according to the assigned treatment sequence, in the presence of the Investigator or authorized site personnel. In addition, patients received two inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding. All patients followed the same sequence of device inhalation, i.e. Symbicort or placebo Turbohaler first and Z7200 or placebo RS-01 inhaler second.

On the second dosing day (Period 2, Visit 3), patients underwent the same asthma stability check and procedures as in Visit 2. Patients received a single dose consisting of two inhalations of the other treatment (reference in case test product was administered at Visit 2 and vice versa) plus two inhalations with matching placebo to the alternate treatment.

Eligibility criteria: Inclusion Criteria:

1. Male or female patient ≥ 18 years old.
2. Written informed consent obtained.
3. Patient with a documented diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines
4. Patient with a co-operative attitude and ability to correctly use the DPI.
5. Female patient of childbearing potential who confirm that a reliable method of contraception was used at least 14 days before visit 1 and will continue to use a reliable method of contraception during the study, or post-menopausal women (at least 12 months of amenorrhea)
6. Patient must be stable and treated in accordance with the GINA guidelines.
7. Patient must be a non-smoker or ex-smoker who have stopped smoking at least 1 month prior to visit 1 and has a smoking history of \< 10 pack years.
8. Patient must be able to understand and complete the protocol requirements, instructions, questionnaires and protocol-stated restrictions.

Exclusion Criteria:

1. Pregnant or lactating female.
2. Unstable patient who developed an asthma exacerbation in the 4 weeks before screening.
3. Patient with upper or lower airways infection in the 4 weeks before screening.
4. Patient unable to perform pulmonary function testing.
5. Patients unable to withdraw fixed combination or long acting bronchodilator inhalation products
6. Patient with an uncontrolled disease or any condition that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.
7. Patient with active lung cancer or any other chronic disease with poor prognosis and /or affecting patient status.
8. Patient with allergy, sensitivity or intolerance to study drugs and/ or study drug formulation ingredients.
9. Patient unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study.
10. Patient who received systemic corticosteroids within the last 4 weeks prior to visit
11. Patient who received any investigational new drug within the last 4 weeks prior to visit 1 and is participating in any clinical trial.
12. Patient with a history of alcohol or substance abuse that in the opinion of the investigator may be of clinical significance
13. Patient with diagnosis of Chronic Obstructive Pulmonary Disease (COPD).
14. Patients who has a lactose intolerance or history of allergy to milk proteins.
15. Patients treated with medications or herbal medicines that are strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, indinavir, nelfinavir, saquinavir, atazanavir, ketoconazole, itraconazole, voriconazole, fluconazole, cyclosporine, mibefradil, nefazodone, clarithromycin, telithromycin, troleandromycin, norfloxacin, ciprofloxacin) or inducers (e.g. phenobarbital, phenytoin, barbiturates, carbamazepine, oxcarbazepine, rifabutin, rifampin, St John's wort) within 2 weeks prior to Screening Visit and during the study.

Primary outcomes:
measure: Total Airway Volume (iVaw)
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Total Airway Resistance (iRaw)
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Number of Deposited Particles Per Pre-defined Airway Section
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
Secondary outcomes:
measure: Spirometry - FEV1
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Spirometry - FVC
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Spirometry - PEF
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Spirometry - MEF25
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Spirometry - MEF50
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Spirometry - FEV1/FVC Ratio
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Body Plethysmography - FRC
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Body Plethysmography - TLC
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Body Plethysmography - Raw
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Body Plethysmography - SRaw
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Inhalation Profile
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: 6MWT
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Borg CR10 Scale (Pre-6MWT)
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: Borg CR10 Scale (Post-6MWT)
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: VAS (Pre-6MWT)
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
measure: VAS (Post-6MWT)
timeFrame: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: Antwerp
Study officials:
affiliation: University Hospital, Antwerp
name: Wilfried De Backer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: