Study to Compare the Effects of Z7200 And Symbicort® Turbohaler on Respiratory Imaging Parameters in Asthmatic Patients

NCT ID: NCT02227394

Last Updated: 2022-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2014-11-30

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.

Conditions

Asthma; Asthma Chronic; Asthma Bronchial; Asthmatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Z7200 - Symbicort® Turbohaler

The patients randomized to this sequence were to receive a single dose consisting of 2 inhalations of the test product (Z7200) on the first dosing day (Period 1, Visit 2), then, after a wash out period of at least 3 days but no more of 31 days, a single dose consisting of 2 inhalations of the reference treatment (Symbicort® Turbohaler) on the second dosing day (Period 2, Visit 3).

Patients were also to receive 2 inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.

Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.

Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.

Group Type: EXPERIMENTAL

Z7200

Intervention Type: DRUG

Total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01).

At visit 2 or 3 (cross-over design)

Symbicort® Turbohaler®

Intervention Type: DRUG

Total dose budesonide/formoterol is 320 mcg/9 mcg. At visit 2 or 3 (cross-over design)

Symbicort® Turbohaler - Z7200

The patients randomized to this sequence were to receive a single dose consisting of 2 inhalations of the reference treatment (Symbicort® Turbohaler) on the first dosing day (Period 1, Visit 2), then, after a wash out period of at least 3 days but no more of 31 days, a single dose consisting of 2 inhalations of the test product (Z7200) on the second dosing day (Period 2, Visit 3).

Patients were also to receive 2 inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.

Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 320 mcg/9 mcg).

Group Type: EXPERIMENTAL

Z7200

Intervention Type: DRUG

Total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01).

At visit 2 or 3 (cross-over design)

Symbicort® Turbohaler®

Intervention Type: DRUG

Total dose budesonide/formoterol is 320 mcg/9 mcg. At visit 2 or 3 (cross-over design)

Interventions

Z7200

Total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01).

At visit 2 or 3 (cross-over design)

Intervention Type: DRUG

Symbicort® Turbohaler®

Total dose budesonide/formoterol is 320 mcg/9 mcg. At visit 2 or 3 (cross-over design)

Intervention Type: DRUG

Other Intervention Names

Test product; Reference product

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FLUIDDA nv

INDUSTRY

Sponsor Role: collaborator

Zambon SpA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wilfried De Backer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Antwerp

Locations

Antwerp University Hospital

Edegem, Antwerp, Belgium

Countries

Belgium

Other Identifiers

2014-002151-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Z7200K02

Identifier Type: -

Identifier Source: org_study_id