A Phase II, 5-way Cross-over Study to Evaluate the Pharmacodynamics of "Nexthaler" Dry Powder Inhaler in COPD Patients

COPD Clinical Trial

— NEXThaler  

Official title:

Phase II, Partial Blind, Randomized, Placebo Controlled, 5-way Cross-over Study to Evaluate the Pharmacodynamics of BDP(Beclomethasone Diproprionate)/B17MP (Beclomethasone-17-Monoproprionate) and FORMOTEROL FUMARATE (FF) Across Two Different Dose Levels of CHF 1535 NEXThaler DPI (Dry Powder Inhaler) and CHF 1535 pMDI (Pressurized Metered-dose Inhaler)in Adult COPD (Chronic Obstructive Pumonary Disease) Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02000609
• Other study ID #: CCD-01535BC1-02
• Status: Completed
• Phase: Phase 2
• Start date: December 2013
• Est. completion date: April 2014

Study information

• Verified date: October 2021
• Source: Chiesi Farmaceutici S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aim is to compare the pharmacodynamic effects (cardiovascular effects- primary variable: Heart rate over 4 hours post dosing- ) after administration of BDP and formoterol administered as CHF 1535 100/6 NEXThaler DPI or CHF1535 pMDI at two different dose levels.

Description:

The effects of both formulations on serum potassium and serum glucose and the general safety and tolerability of study treatments will be also evaluated

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male and female adults (= 40 and = 75 years old).

• Outpatients with diagnosis of moderate/severe stable COPD, according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines update 2013 at least in the 6 months before the screening visit.

• A post-bronchodilator FEV1(Forced Expiratory Volume in one second) = 40 and < 80% of the predicted normal value and FEV1/FVC (Forced Vital Capacity) < 0.7, after 4 puffs (4 x 100 µg) of salbutamol pMDI. If this criterion is not met at screening, the test can be repeated once before commencing of the run-in period.

• Ability to use pMDI (pressured metered-dose inhaler)and DPI (dry powder Inhaler) devices

• Current or past smoker of at least 10 pack/years where one pack-year is equivalent to 20 cigarettes per day for 1 year

Exclusion Criteria:

• Pregnant or lactating female subjects.

• Current diagnosis of Asthma (as defined by the current GINA (Global Initiative for Asthma guidelines 2012 (update), or history of allergic rhinitis.

• COPD exacerbations requiring systemic steroids and /or antibiotics and/or oral or nebulized beta 2-agonists in the 4 weeks prior to screening and until randomization.

• Lower Respiratory Tract Infection (LRTI) in the 4 weeks prior to screening and until randomization.

• Patients with serum potassium levels < 3.5 mEq/L (milliequivalent per liter).

• History of substance abuse or drug abuse within 12 months prior to screening visit.

• Known respiratory disorders other than COPD including but not limited to a1 antitrypsin deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, restrictive lung disease and interstitial lung disease.

• Intolerance or contra-indication to treatment with beta 2-agonists and/or inhaled corticosteroids or allergy to any component of the study treatments.

• Patients treated with non-cardioselective ß-blockers in the month preceding the screening visit or during the study period.

• Patients who have clinically significant cardiovascular disease according to investigator's judgement. Thus includes but is not limited to:

• congestive heart failure (NYHA class > 3);

• acute ischemic heart disease within the past 12 months of screening;

• Sustained cardiac arrhythmias (supraventricular or ventricular, >30 seconds duration) at or within 6 months of screening;

• Non sustained cardiac arrhythmias (supraventricular or ventricular, > 3 beats < 30 seconds and or ending spontaneously and or asymptomatic);

• History of sustained and non-sustained cardiac arrhythmias (supraventricular or ventricular);

• 2nd or 3rd degree Atrioventricular conduction block;

• Left Bundle Branch Block.

• An abnormal 12-lead ECG (QRS> 120 msec, PR> 220 msec, HR < 40 bpm, Heart Rate > 110 bpm) at screening or at randomization.

• Patients whose electrocardiogram (12-lead ECG) shows QTcF >450 ms for males or QTcF > 470 ms for females at screening or at randomisation.

• Patients whose DBP/SBP is higher than: DBP 90 mmHg or SBP 160 mmHg at screening or at randomization.

Related Conditions & MeSH terms

• COPD

Intervention

Drug:
• CHF 1535 NEXThaler 800/48

• CHF 1535 NEXThaler 200/12

• CHF 1535 NEXThaler PLACEBO

• CHF 1535 pMDI 200/12

• CHF1535 pMDI 800/48

Locations

Country	Name	City	State
United Kingdom	Medicine Evaluation Unit	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Chiesi Farmaceutici S.p.A.

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Singh D, Ciurlia G, Piccinno A, Muraro A, Bocchi M, Scuri M. Acute cardiovascular safety of two formulations of beclometasone dipropionate/formoterol fumarate in COPD patients: A single-dose, randomised, placebo-controlled crossover study. Pulm Pharmacol — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average 4-hour Heart Rate bpm (beats per minutes)		4 hours
Secondary	QTcF (QT interval Fridericia's formula corrected) (milliseconds), QRS (milliseconds) and PR (milliseconds) intervals, PAC (Premature Atrial Contraction- percentage) burden, PVC (Premature Ventricular Contraction-percentage) burden, Blood Pressure (mmHg)		-45, -30, -15min pre-dose, 5, 10, 20, 30, 45min, 1, 1.5, 2, 3, 4, 5, 5, 7, 8, 10 12 hr post dose

External Links

•   CSR Synopsis available in the CHIESI Clinical Study Register
•   Study Record on EU Clinical Trials Register including results