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

Chiesi

Status and phase: Completed; Phase 1

Conditions: Asthma; Chronic Obstructive Pulmonary Disease (COPD)

Treatments: Drug: CHF5993 Placebo; Drug: CHF5259; Drug: CHF5993; Drug: Moxifloxacin 400mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05830071

CLI-05993AB7-03

Details and patient eligibility

About

The purpose of this study is to evaluate the potential for cardiac repolarization, according to electrocardiographic monitoring (including QT and QTc intervals), of two dose levels of CHF5993 pMDI (beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB)) and of one dose of CHF5259 (GB) in healthy subjects compared to moxifloxacin and placebo.

Full description

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.

Enrollment: 95 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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95 participants in 5 patient groups, including a placebo group

Single therapeutic dose of CHF5993 (BDP/FF/GB)

Experimental group

Description:

Dose: BDP/FF/GB 100/6/12.5 μg, single dose inhalation via pressurized metered dose inhaler (2 puffs from 1 BDP/FF/GB 100/6/12.5 μg pMDI + 2 puffs from 3 placebo pMDI)

Treatment:

Drug: CHF5993

Drug: CHF5993 Placebo

Single supra-therapeutic dose of CHF5993 (BDP/FF/GB)

Experimental group

Description:

Dose: BDP/FF/GB 800/48/100 μg single dose inhalation, via pressurized metered dose inhaler (8 puffs from 4 BDP/FF/GB 100/6/12.5 μg pMDI)

Treatment:

Drug: CHF5993

Single supra-therapeutic dose CHF5259 (GB)

Experimental group

Description:

Dose: GB 100 μg single dose inhalation, via pressurized metered dose inhaler (8 puffs from 4 GB 12.5 μg pMDI)

Treatment:

Drug: CHF5259

Single dose Placebo

Placebo Comparator group

Description:

Dose: placebo single dose inhalation, via pressurized metered dose inhaler 8 puffs from 4 CHF5993 placebo pMDI

Treatment:

Drug: CHF5993 Placebo

Moxifloxacin

Active Comparator group

Description:

Dose: moxifloxacin 400 mg single dose, for oral use - open label treatment (1 tablet of moxifloxacin 400 mg PO)

Treatment:

Drug: Moxifloxacin 400mg