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

NCT02000609 | Completed Phase 2

• 1 other identifier: CCD-01535BC1-02
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COPD

Keywords

pharmacodynamics COPD

Outcome Measures

Primary Outcomes (1)

• Average 4-hour Heart Rate bpm (beats per minutes)

  4 hours

Secondary Outcomes (1)

• 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

Study Arms (5)

CHF 1535 NEXThaler 800/48 ug

ACTIVE COMPARATOR

single dose administration of CHF 1535 100/6 NEXThaler DPI, total dose: 800ug BDP, 48 ug Formoterol Fumarate

Drug: CHF 1535 NEXThaler 800/48

CHF 1535 NEXThaler PLACEBO

PLACEBO COMPARATOR

single dose administration of placebo via NEXThaler DPI

Drug: CHF 1535 NEXThaler PLACEBO

CHF 1535 pMDI 200/12

ACTIVE COMPARATOR

single dose administration of CHF 1535 100/6 pMDI , total dose: 200 ug BDP, 12 ug Formoterol Fumarate

Drug: CHF 1535 pMDI 200/12

CHF 1535 100/6 pMDI 800/48

ACTIVE COMPARATOR

single dose administration of CHF 1535 100/6 pMDI total dose: 800ug BDP, 48 ug Formoterol Fumarate

Drug: CHF1535 pMDI 800/48

CHF 1535 NEXThaler 200/12

ACTIVE COMPARATOR

single dose administration of CHF 1535 100/6 pMDI, total dose: 200 ug BDP, 12 ug Formoterol Fumarate

Drug: CHF 1535 NEXThaler 200/12

Interventions

CHF 1535 NEXThaler 800/48 DRUG

CHF 1535 NEXThaler 800/48 ug

CHF 1535 NEXThaler 200/12 DRUG

CHF 1535 NEXThaler 200/12

CHF 1535 NEXThaler PLACEBO DRUG

CHF 1535 NEXThaler PLACEBO

CHF 1535 pMDI 200/12 DRUG

CHF 1535 pMDI 200/12

CHF1535 pMDI 800/48 DRUG

CHF 1535 100/6 pMDI 800/48

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 α1 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 β-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);

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

Medicine Evaluation Unit

Manchester, M239Qz, United Kingdom

Location

Related 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 Ther. 2017 Feb;42:43-51. doi: 10.1016/j.pupt.2016.12.004. Epub 2017 Jan 5.

  PMID: 28065679 RESULT

Related Links

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

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dave Singh

  Medicine Evaluation Unit, Manchester (UK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2013
• First Posted: December 4, 2013
• Study Start: December 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: October 29, 2021

Record last verified: 2021-10

Locations

GB (1)