Fixed airflow obstruction with elevated eosinophils MedDRA version: 18.1 Level: LLT Classification code 10077006 Term: Asthma-COPD overlap syndrome System Organ Class: 100000004855
Conditions
Interventions
Trade Name: flutiform® 125 microgram / 5 microgram per actuation pressurised inhalation, suspension
Product Name: Fluticasone/formoterol BAI 125/5 µg
Product Code: K-haler
Pharmaceutical Form: Pressur
Sponsors
Mundipharma Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged = 40 years at Screening visit. 2. Adequate contraception: - Female subjects of child bearing potential (less than 1 year post-menopausal) must have a negative urine pregnancy test prior to first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of birth control throughout the study such as sterilisation, implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence, where this is line with the preferred and usual lifestyle of the subject or vasectomised partner. Note: Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for duration of study, and withdrawal are not acceptable methods of contraception). - Male subjects with a partner of child-bearing potential must be willing to use adequate and highly effective methods of birth control throughout the study (as defined above). 3. Diagnosis of fixed airflow obstruction with elevated eosinophils /ACOS as evidenced by: - Chronic respiratory symptoms e.g. wheezing, dyspnoea, especially exertional dyspnoea) for at least 6 months prior to Screening. - Smoking history of = 10 pack years (equivalent to, for example, 20 cigarettes/day for 10 years or 10 cigarettes/day for 20 years). - Post-bronchodilator FEV1 / FVC ratio 30 and =65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. Respiratory disease exacerbation between 4 weeks prior to screening and Visit 3 (Randomisation). 2. Previous treatment with ICS. 3. Documented evidence of a1-antitrypsin deficiency. 4. Other active respiratory disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung disease, cystic fibrosis, bronchiolitis obliterans. 5. Use of long-term oxygen therapy (LTOT) at least 12 hours daily or mechanical ventilation. 6. Chest X-ray or CT scans performed prior to screening which reveal evidence of clinically significant abnormalities reflective of active disease not believed to be due to COPD. 7. Evidence of uncontrolled cardiovascular disease. 8. Evidence of clinically significant renal, hepatic, gastrointestinal, or psychiatric disease. 9. Current malignancy or a previous history of cancer which has been in remission for < 5 years (basal cell or squamous cell carcinoma of the skin which has been resected is not excluded). 10. Clinically significant sleep apnoea requiring use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device. 11. Participation in the acute phase of a pulmonary rehabilitation programme within 4 weeks prior to screening or during the study. 12. Known or suspected history of drug or alcohol abuse in the last 2 years. 13. Requiring treatment with any of the prohibited concomitant medications. 14. Known or suspected hypersensitivity or contraindication to any of the study drugs or excipients. 15. Received an investigational drug within 30 days of the Screening. 16. Received a systemic corticosteroid within 30 days of the Screening visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of fluticasone /formoterol BAI 125/5 µg (2 puffs b.i.d.) versus Ultibro Breezhaler 85/43 µg (1 puff o.d.) in terms of the percentage of eosinophils in induced sputum at Week 6 of each treatment.;Secondary Objective: Key Secondary Objective: To compare the efficacy of fluticasone /formoterol BAI 125/5 µg (2 puffs b.i.d.) versus Ultibro Breezhaler 85/43 µg (1 puff o.d.) in terms of the serum concentration of SPD at Week 6 of each treatment. Only the Key Secondary Objective is listed here. Please refer to section 7.3 of the protocol (Final Version 2.0, 26 Nov 2015) for the full list of Secondary Objectives. ;Primary end point(s): Change from baseline in eosinophil count (percentage of total cell count) in induced sputum at Week 6;Timepoint(s) of evaluation of this end point: Evaluation after study end. No interim analysis planned. Please refer to section 14.21 of the protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary efficacy endpoint: Change from baseline in serum concentration of the SPD at Week 6 Other secondary efficacy endpoints: • Change from baseline in percentage of blood eosinophils at Week 6 • Change from baseline in serum concentration of CCL-18 at Week 6 • Change from baseline in concentration of nitric oxide in exhaled air (bronchial FENO) at Week 3 and Week 6 (exhaled at 50 mL/s) • Change from baseline in alveolar nitric oxide (in a subgroup of subjects) at Week 3 and Week 6 measured at 50, 100 and 150mL/sec • Change from baseline in EXACT-respiratory symptoms (EXACT-RS) dyspnoea score averaged over 6-week treatment period • Changes from baseline in EXACT total score averaged over the 6-week treatment period • Changes from baseline in mean rescue medication use measured morning and evening over 6 weeks of treatment • Change from baseline in ACQ at Week 6 • Change from baseline in CAT at Week 6 • Changes from baseline in pre-dose FEV1 & FVC at Week 6 • Changes from baseline in mean peak expiratory flow rate (PEFR) measured morning and evening (prior to taking study medication) over 6 weeks of treatment using electronic subject diary • Change from baseline in oscillometric parameters (R5, R20, R5 - R20, AX, RF, X5) at Week 6 of each treatment (in a subgroup) • Change from baseline in percentage of neutrophils, macrophages and lymphocytes in induced sputum at Week 6 of each treatment. ;Timepoint(s) of evaluation of this end point: Evaluation after study end. No interim analysis planned. Please refer to section 14.21 of the protocol. | — |
Countries
Bulgaria, Hungary, Italy, Poland, Romania, Slovakia, Spain, Ukraine
Contacts
Public ContactProject Management
Scope International AG
Outcome results
None listed