Clinical trial NCT02000609: A Phase II, 5-way Cross-over Study to Evaluate the Pharmacodynamics of "Nexthaler" Dry Powder Inhaler in COPD Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COPD
Keywords: pharmacodynamics COPD
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2013-12-04
Enrollment: 49
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Detailed 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

Eligibility criteria: 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 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);
  * 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.

Primary outcomes:
measure: Average 4-hour Heart Rate bpm (beats per minutes)
timeFrame: 4 hours
Secondary outcomes:
measure: 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)
timeFrame: -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
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Medicine Evaluation Unit
Study officials:
affiliation: Medicine Evaluation Unit, Manchester (UK)
name: Dave Singh
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.