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

NCT ID: NCT05830071

Last Updated: 2024-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-29
• Study Completion Date: 2023-10-13

Brief Summary

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.

Detailed 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.

Conditions

Asthma; Chronic Obstructive Pulmonary Disease (COPD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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

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)

Group Type: EXPERIMENTAL

CHF5993

Intervention Type: DRUG

BDP/FF/GB 100/6/12.5 μg pMDI

CHF5993 Placebo

Intervention Type: DRUG

placebo pMDI

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

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)

Group Type: EXPERIMENTAL

CHF5993

Intervention Type: DRUG

BDP/FF/GB 100/6/12.5 μg pMDI

Single supra-therapeutic dose CHF5259 (GB)

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

Group Type: EXPERIMENTAL

CHF5259

Intervention Type: DRUG

GB 12.5 μg pMDI

Single dose Placebo

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

Group Type: PLACEBO_COMPARATOR

CHF5993 Placebo

Intervention Type: DRUG

placebo pMDI

Moxifloxacin

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

Group Type: ACTIVE_COMPARATOR

Moxifloxacin 400mg

Intervention Type: DRUG

400 mg Oral Tablets

Interventions

CHF5993

BDP/FF/GB 100/6/12.5 μg pMDI

Intervention Type: DRUG

CHF5259

GB 12.5 μg pMDI

Intervention Type: DRUG

Moxifloxacin 400mg

400 mg Oral Tablets

Intervention Type: DRUG

CHF5993 Placebo

placebo pMDI

Intervention Type: DRUG

Other Intervention Names

beclometasone dipropionate /formoterol fumarate/glycopyrronium bromide; BDP/FF/GB; glycopyrronium bromide; GB; Moxifloxacin hydrochloride; BDP/FF/GB Placebo

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald Goldwater, MDCM/M.SC(A)

Role: PRINCIPAL_INVESTIGATOR

PAREXEL Baltimore Early Phase Clinical Unit

Locations

PAREXEL Baltimore Early Phase Clinical Unit

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

CLI-05993AB7-03

Identifier Type: -

Identifier Source: org_study_id