A Thorough QT (TQT) Study of CHF5993 pMDI in Healthy Volunteers (HV)

The main purpose of this study is to evaluate the effect of a single supratherapeutic dose of inhaled BDP/FF/GB on cardiovascular safety. The secondary purposes of the study are to: 1) evaluate the effect of a single supratherapeutic dose of inhaled BDP/FF/GB and GB on cardiovascular safety; 2) establish assay sensitivity by demonstrating the effect of a single oral dose of 400 mg moxifloxacin on cardiovascular safety; 3) determine the pharmacokinetics (PK) of single, inhaled therapeutic and supratherapeutic BDP/FF/GB doses and supratherapeutic GB dose; 4) determine if there is a relationship between the duration of the QTc intervals and the plasma concentrations of the B17MP (beclomethasone 17monopropionate active metabolite of BDP), FF and GB following the administration of BDP/FF/GB and GB pMDIs; 5) generate additional safety and tolerability information.

Key Inclusion Criteria:

• Subject's written informed consent;
• 18-55 years of age;
• Ability to understand the study procedures, the risks involved and ability to be trained to use the inhalers correctly;
• Body Mass Index (BMI) between 18 and 32 kg/m2 extremes inclusive;
• Non- or ex-smokers who smoked < 5 pack years and stopped smoking > 1 year prior to screening;
• Good physical and mental status, determined on the basis of the medical history and a general clinical examination;
• Vital signs within normal limits at screening and prior to randomization: Diastolic BP 40-89 mmHg, Systolic BP 90-139 mmHg extremes included (mean value of three measures). Body temperature < 37.5°C;
• 12 -lead digitized Electrocardiogram (12-lead ECG) in triplicate considered as normal (40 ≤ Heart rate ≤ 110bpm, 120 ms ≤ PR ≤ 220 ms, QRS ≤ 110 ms, QTcF ≤ 450 ms);
• Lung function measurements within normal limits (normal values: forced expiratory volume in the 1st second [FEV1]/forced vital capacity [FVC] > 0.70 and FEV1 > 80% predicted);
• Female subjects of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods.

Key Exclusion Criteria:

• Participation in another clinical trial where investigational drug was received and last investigations within the last 8 weeks;
• Clinically significant abnormal standard ECG at screening;
• Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic, or psychiatric disorders that may interfere with successful completion of this protocol;
• Subjects 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;
• Subjects with history of breathing problems (i.e., history of asthma including childhood asthma);
• Positive urine test for cotinine;
• Intake of non-permitted concomitant medications in the predefined period prior to screening or prior to randomization, or the subject is expected to take non-permitted concomitant medications during the study;
• Presence of any current infection, or previous infection that resolved less than 7 days prior to screening or to randomization;
• Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the trial;
• Women who are pregnant or lactating;
• Use of any kind of smoking electronic devices within 6 months before Screening.

Other inclusion/exclusion criteria as defined by the protocol.