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

NCT05830071 | Completed Phase 1 FDA Drug

• 1 other identifier: CLI-05993AB7-03
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Chronic Obstructive Pulmonary Disease (COPD)

Outcome Measures

Primary Outcomes (1)

• Effect of BDP/FF/GB pMDI at therapeutic dose on the heart rate-corrected QT interval based on the Fridericia's correction (QTcF).

  Placebo-adjusted change in QTc interval based on the Fridericia's correction (ΔΔQTcF) after dosing CHF5993 pMDI (200/12/25 μg). Through digitised 12-lead ECG, extracted from 12-Lead Holter ECG.

  time 0 (pre-dose) to 24 hours

Secondary Outcomes (21)

• Effect of BDP/FF/GB pMDI and GB pMDI at supra-therapeutic dose on the heart rate-corrected QT interval based on the Fridericia's correction (QTcF).

  time 0 (pre-dose) to 24 hours

• Assay sensitivity by demonstrating the effect of a single oral therapeutic dose of moxifloxacin on QTcF.

  time 0 (pre-dose) to 6 hours

• Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on Hearth Rate (HR).

  time 0 (pre-dose) to 24 hours

• Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on PR interval (PR).

  time 0 (pre-dose) to 24 hours

• Effect of BDP/FF/GB pMDI at therapeutic and supra-therapeutic dose and of GB pMDI at supra-therapeutic dose on QRS interval (QRS).

  time 0 (pre-dose) to 24 hours

Study Arms (5)

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

EXPERIMENTAL

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)

Drug: CHF5993; Drug: CHF5993 Placebo

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

EXPERIMENTAL

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)

Drug: CHF5993

Single supra-therapeutic dose CHF5259 (GB)

EXPERIMENTAL

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

Drug: CHF5259

Single dose Placebo

PLACEBO COMPARATOR

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

Drug: CHF5993 Placebo

Moxifloxacin

ACTIVE COMPARATOR

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

Drug: Moxifloxacin 400mg

Interventions

CHF5993 DRUG

BDP/FF/GB 100/6/12.5 μg pMDI

Also known as: beclometasone dipropionate /formoterol fumarate/glycopyrronium bromide, BDP/FF/GB

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

CHF5259 DRUG

GB 12.5 μg pMDI

Also known as: glycopyrronium bromide, GB

Single supra-therapeutic dose CHF5259 (GB)

Moxifloxacin 400mg DRUG

400 mg Oral Tablets

Also known as: Moxifloxacin hydrochloride

Moxifloxacin

CHF5993 Placebo DRUG

placebo pMDI

Also known as: BDP/FF/GB Placebo

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject's written informed consent;
• 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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

PAREXEL Baltimore Early Phase Clinical Unit

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Interventions

Beclomethasone; Formoterol Fumarate; Glycopyrrolate; Moxifloxacin

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Quaternary Ammonium Compounds; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ronald Goldwater, MDCM/M.SC(A)

  PAREXEL Baltimore Early Phase Clinical Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 26, 2023
• Study Start: March 29, 2023
• Primary Completion: October 13, 2023
• Study Completion: October 13, 2023
• Last Updated: September 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)