Study to Evaluate Efficacy/Safety of 4 Doses of CHF5259 Via Dry Powder Inhaler (DPI) in Patients With COPD

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— GlycoNEXT  

Official title:

Randomised, Double Blind, Placebo-controlled, Incomplete Block, 3-way Cross-over Study to Evaluate Efficacy and Safety of 4 Doses of Glycopyrronium Bromide (CHF5259) DPI in Moderate to Severe Patients With COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02680197
• Other study ID #: CCD-06302AA1-01
• Secondary ID: 2015-000558-40
• Status: Completed
• Phase: Phase 2
• Start date: February 29, 2016
• Est. completion date: February 6, 2017

Study information

• Verified date: July 2020
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study was designed to investigate the efficacy and safety of different doses CHF5259 a long acting muscarinic antagonist in patients with moderate to severe COPD.

Description:

Outpatients attending the hospital clinics/study centres will be recruited. Patients with moderate to severe COPD airflow obstruction according to GOLD 2015 criteria.

A total of approximately 300 patients will be enrolled.

Patients are followed during 3 different treatment periods of 4 weeks separated each by 3 weeks wash-out period. The study lasts approximately 21 weeks for each patient and a total of 11 clinic visits is performed during the study.

The primary endpoint is the Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) 0-12h normalised by time on Day 28.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 262
• Est. completion date: February 6, 2017
• Est. primary completion date: February 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Male or female patients aged = 40 years

2. Patients with a diagnosis of stable COPD at least 12 months before screening visit.

3. Current smoker or ex-smoker with a smoking history of at least 10 pack-years

4. - A post-bronchodilator FEV1 = 40% and =70% of the predicted normal value and,

• a post-bronchodilator FEV1/FVC < 0.7 and,

• a change in FEV1 from the pre-bronchodilator value (reversibility) of at least 5% at screening

5. Patients under bronchodilators with long-acting muscarinic antagonist or long-acting 2 agonist (monotherapy or dual therapy), or patients under ICS + LABA (long-acting beta2-agonist) or ICS (Inhaled Corticosteroids) + LAMA (Long Acting Muscarinic Agonist) for at least 4 weeks prior to screening.

(Patients with a FEV1<50% of the predicted value and a history of 1 exacerbation within the last 12 months must have been treated with ICS+LABA or ICS+LAMA before screening)

6. Ability and cooperative attitude to understand and to perform required outcome measurements of the protocol (e.g. spirometry manoeuvres) and ability to understand the risks involved. Ability to be trained to use the dry powder inhalers.

Exclusion Criteria:

1. Diagnosis of asthma or other respiratory disorders (other than COPD) which may interfere with data interpretation according to the investigator's opinion.

2. Patients had a COPD exacerbation or a lower respiratory tract infection within 8 weeks prior to screening, or during the run-in period, that resulted in the use of an antibiotic, or oral or parenteral corticosteroids, or hospitalisation.

3. Patients with a history of = 2 exacerbations within the last 12 months prior to screening.

4. Patients treated with oral/parenteral ß2-agonists or nebulised bronchodilators or phosphodiesterase inhibitors or who received LABA/LAMA/ICS treatment therapy in the 4 weeks prior to screening and during the run-in period.

5. Patient is on an inhaled corticosteroid that has been initiated, or the effective dose has been changed, within 4 weeks prior to screening or during the run-in period (patients on stable dose of ICS for at least 4 weeks prior to screening are allowed).

6. Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.

7. Patients with known respiratory disorders other than COPD including but not limited to alpha1 antitrypsin deficiency, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease.

8. Patients with medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic.

9. Patients who have unstable concurrent disease that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study;

10. Patients who have a concomitant disease of poor prognosis (e.g., cancer...).

11. Patients who have clinically significant cardiovascular condition diagnosed in the last 6 months

12. Patients with known atrial fibrillation (AF):

1. Paroxysmal Atrial Fibrillation

2. Persistent

3. Long standing persistent.

4. Permanent

13. Patients with a clinically significant abnormal 12-lead ECG that might, in the judgment of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.

14. Patients whose electrocardiogram 12-lead ECG shows a QTcF>450 ms for males or QTcF > 470 ms for females.

15. Patients with clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.

16. Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS they are willing to use a highly effective birth control methods

17. Patients known to have intolerance/hypersensitivity or any contra-indication to treatment with M3 Antagonist or any of the excipients contained in the formulations used in the study.

18. Patients who have evidence of alcohol or drug abuse, not compliant with the study protocol or not compliant with the study treatments according to investigator's judgment.

19. Patients with major surgery in the previous 3 months or planned during the trial which may affect patient's compliance in study procedures.

20. Patients who have participated in another clinical trial with an investigational drug in the 2 months preceding the screening.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• CHF5259 or Placebo administration
Administration of 2 puffs of treatment in the morning and in the evening during a 4 week period. Each patient will be allocated to 3 out of the 5 possible treatments.

Locations

Country	Name	City	State
Czechia	Clinical Trial Site 203-002	Karlovy Vary
Czechia	Clinical Trial Site 203-003	Kralupy nad Vltavou
Czechia	Clinical Trial Site 203-001	Melnik
Czechia	Clinical Trial Site 203-007	Mlada Boleslav
Czechia	Clinical Trial Site 203-005	Moravský Krumlov
Czechia	Clinical Trial Site 203-006	Teplice
Czechia	Clinical Trial Site 203-004	Varnsdorf
Germany	Clinical Trial Site 276-003	Bonn
Germany	Clinical Trial Site 276-004	Cottbus
Germany	Clinical Trial Site 276-006	Freiburg
Germany	Clinical Trial Site 276-002	Grosshansdorf
Germany	Clinical Trial Site 276-005	Stuttgart
Germany	Clinical Trial Site 276-001	Wiesbaden
Hungary	Clinical Trail Site 348-006	Budapest
Hungary	Clinical Trial Site 348-003	Budapest
Hungary	Clinical Trial Site 348-004	Budapest
Hungary	Clinical Trial Site 348-001	Deszk
Hungary	Clinical Trial Site 348-005	Komarom
Hungary	Clinical Trial Site 348-002	Létavértes
Hungary	Clinical Trail Site 348-008	Miskolc
Hungary	Clinical Trail Site 348-009	Seregélyes
Hungary	Clinical Trail Site 348-007	Szombathely
Romania	Clinical Trial Site 642-005	Bacau
Romania	Clinical Trial Site 642-003	Brasov
Romania	Clinical Trial Site 642-007	Bucharest
Romania	Clinical Trial Site 642-008	Bucharest
Romania	Clinical Trial Site 642-004	Cluj-Napoca
Romania	Clinical Trial Site 642-001	Codlea
Romania	Clinical Trial Site 642-002	Miercurea Ciuc
Romania	Clinical Trial Site 642-006	Suceava

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Countries where clinical trial is conducted

Czechia,  Germany,  Hungary,  Romania, 

References & Publications (1)

Beeh KM, Emirova A, Prunier H, Santoro D, Nandeuil MA. Dose-response of an extrafine dry powder inhaler formulation of glycopyrronium bromide: randomized, double-blind, placebo-controlled, dose-ranging study (GlycoNEXT). Int J Chron Obstruct Pulmon Dis. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FEV1 AUC0-12h normalised by time (L)		Day 28
Secondary	Change from baseline in morning pre-dose FEV1 (L)		Day 28
Secondary	Change from baseline in morning pre-dose FEV1 (L)		Day 14
Secondary	Peak0-4h effect in FEV1 (L)		Day 28
Secondary	Adverse events and adverse drug reactions		Day 28
Secondary	Change from baseline in morning pre-dose Forced Vital Capacity FVC (L)		Day 28
Secondary	Change from baseline in morning pre-dose FVC (L)		Day 14
Secondary	Change from baseline in morning pre-dose Inspiratory Capacity IC (L)		Day 28
Secondary	Change from baseline in morning pre-dose IC (L)		Day 14

External Links

•   Study Record on EU Clinical Trials Register including results