Clinical Study to Evaluate the Safety, Tolerability and the Concentration of the BDP (Beclomethasone Dipropionate), Active Metabolite of BDP, FF( Formoterol Fumarate) and GB (Glycopyrronium Bromide), After Inhalation of CHF 5993 at Two Different Doses and QVAR®

NCT ID: NCT05898984

Last Updated: 2024-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-24
• Study Completion Date: 2023-07-14

Brief Summary

The study is being conducted to compare the pharmacokinetic (PK) of BDP (and its main active metabolite B17MP), FF, and GB between CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI and CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI (pressurized Metered Dose Inhaler), to assess the proportionality of systemic exposure to BDP and B17MP (17-Monoproprionate), and the systemic exposure to FF and GB with increasing doses of BDP.

The study includes a QVAR REDIHALER® arm too.

Detailed Description

The main purpose of this study is to evaluate the systemic exposure to B17MP, FF, and GB as the area under the concentration-time curve from zero to time 't' where t is the last quantifiable time point (AUC0-t) and maximum plasma concentration (Cmax) across two different dose strengths of CHF 5993 BDP/FF/GB (200/6/12.5 μg and 100/6/12.5 μg).

The secondary purposes of the study are:

1. To evaluate the pharmacokinetic profile of BDP and additional pharmacokinetic parameters of B17MP, FF, and GB across two different dose strengths of CHF 5993 BDP/FF/GB (200/6/12.5 μg and 100/6/12.5 μg);

2. To compare the exposure to BDP and B17MP between the high dose BDP/FF/GB (total daily dose [TDD]: 800/24/50 µg) and the highest US-approved dose of QVAR (TDD 800 µg).

3. generate additional safety and tolerability information of the two CHF 5993 pDMI strengths, after a single dose.

Participation in the study will last for a maximum of 70 days for each subject (starting from randomization).

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

single dose of CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI (T)

CHF 5993 BDP/FF/GB 200/6/12.5 µg via pressurized metered dose inhaler: 4 inhalations alternated with 4 inhalations of CHF 5993 placebo, corresponding to 8 inhalations in total and giving a total daily dose (TDD) of BDP/FF/GB: 800/24/50 µg.

Group Type: EXPERIMENTAL

Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI

Intervention Type: DRUG

CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI with HFA 134a propellant (fixed combination of BDP [200 μg], FF [6 μg] and GB [12.5 μg] via pMDI): 4 inhalations alternated with 4 inhalations of CHF 5993 placebo, corresponding to 8 inhalations in total and giving a total daily dose (TDD) of BDP/FF/GB: 800/24/50 µg.

Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI with HFA 134a propellant (fixed combination of BDP [100 μg], FF [6 μg] and GB [12.5 μg] via pMDI): 4 inhalations alternated with 4 inhalations of CHF 5993 placebo, corresponding to 8 inhalations in total and giving a TDD of BDP/FF/GB: 400/24/50 µg.

Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg): pressurised, breath-actuated, metered dose aerosol with a dose counter): 8 inhalations (TDD of BDP: 640 µg ex-actuator, 800 µg ex valve).

single dose of CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI (R1)

CHF 5993 BDP/FF/GB 100/6/12.5 µg via pressurized metered dose inhaler: 4 inhalations alternated with 4 inhalations of CHF 5993 placebo, corresponding to 8 inhalations in total and giving a TDD of BDP/FF/GB: 400/24/50 µg.

Group Type: ACTIVE_COMPARATOR

Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI

Intervention Type: DRUG

with HFA 134a propellant (fixed combination of BDP \[100 μg\], FF \[6 μg\] and GB \[12.5 μg\] via pMDI): 4 inhalations alternated with 4 inhalations of CHF 5993 placebo, corresponding to 8 inhalations in total and giving a TDD of BDP/FF/GB: 400/24/50 µg

Single dose of BDP HFA (QVAR REDIHALER®, BDP 80 μg) (R2)

BDP HFA (QVAR REDIHALER®, BDP 80 μg): pressurised, breath-actuated, metered dose aerosol with a dose counter): 8 inhalations (TDD of BDP: 640 µg ex-actuator, 800 µg ex valve).

Group Type: ACTIVE_COMPARATOR

Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg)

Intervention Type: DRUG

pressurised, breath-actuated, metered dose aerosol with a dose counter): 8 inhalations (TDD of BDP: 640 µg ex-actuator, 800 µg ex valve).

Interventions

Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI

CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI with HFA 134a propellant (fixed combination of BDP [200 μg], FF [6 μg] and GB [12.5 μg] via pMDI): 4 inhalations alternated with 4 inhalations of CHF 5993 placebo, corresponding to 8 inhalations in total and giving a total daily dose (TDD) of BDP/FF/GB: 800/24/50 µg.

Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI with HFA 134a propellant (fixed combination of BDP [100 μg], FF [6 μg] and GB [12.5 μg] via pMDI): 4 inhalations alternated with 4 inhalations of CHF 5993 placebo, corresponding to 8 inhalations in total and giving a TDD of BDP/FF/GB: 400/24/50 µg.

Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg): pressurised, breath-actuated, metered dose aerosol with a dose counter): 8 inhalations (TDD of BDP: 640 µg ex-actuator, 800 µg ex valve).

Intervention Type: DRUG

Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI

with HFA 134a propellant (fixed combination of BDP \[100 μg\], FF \[6 μg\] and GB \[12.5 μg\] via pMDI): 4 inhalations alternated with 4 inhalations of CHF 5993 placebo, corresponding to 8 inhalations in total and giving a TDD of BDP/FF/GB: 400/24/50 µg

Intervention Type: DRUG

Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg)

pressurised, breath-actuated, metered dose aerosol with a dose counter): 8 inhalations (TDD of BDP: 640 µg ex-actuator, 800 µg ex valve).

Intervention Type: DRUG

Other Intervention Names

Trimbow Medium Strenght (MS)®; QVAR REDIHALER®

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 correctly use the inhalers.
• Body mass index of 19.0 to 30.0 kg/m2 (extremes inclusive), and body weight ≥50.0 kg;
• Non- or ex-smokers who smoked <5 pack-years and stopped smoking >1 year prior to screening;
• Good physical and mental status, determined based on the medical history and a general clinical examination;
• Vital signs within normal limits at screening: diastolic blood pressure (DBP) 40 to 90 mmHg, systolic blood pressure (SBP) 90 to 140 mmHg
• 12-Lead digitised electrocardiogram (ECG) in triplicate considered as normal (40 ≤ heart rate [HR] ≤110 beats per minute, 120 milliseconds [ms] ≤ PR interval [PR] ≤220 ms [PR ≤120 ms without a delta wave may be acceptable], QRS interval [QRS] ≤120 ms, and Fridericia corrected QT interval [QTcF] ≤450 ms for males and QTcF ≤470 ms for females).
• Lung function measurements within normal limits at screening: forced expiratory volume in the first second (FEV1) equal to or more than 80% of predicted for the subject's normal value according to the Global Lung Function Initiative, European Respiratory Society Task Force Lung Function Reference Values and FEV1/forced vital capacity ratio >0.70.
• Female subjects of non-chid bearing potential or females of childbearing potential with a negative pregnancy test and acceptable contraceptive methods.

Exclusion Criteria

• Participation in another clinical study with an investigational drug in the 30 days or five half-lives of that investigational drug (whichever is longer) preceding the administration of the study treatment; longer and more appropriate time could be considered by the Investigator based on the terminal half-life (t1/2) and/or long-term toxicity of the previous investigational drug;
• Clinically relevant and uncontrolled respiratory, cardiac, hepatic, gastrointestinal, renal, endocrine, metabolic, neurologic or psychiatric disorders that may interfere with successful completion of this protocol according to the Investigator's judgment;
• 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 randomisation 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 prior to randomisation;
• Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation used in the study;
• 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 anticholinergics;
• For females only: pregnant or lactating women.
• Subjects receiving treatment with any drug known to have a well defined potential for hepatotoxicity.
• Subjects using e-cigarettes within 6 months before screening.

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

Sponsors

SGS S.A.

INDUSTRY

Sponsor Role: collaborator

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jelle Klein, MD

Role: PRINCIPAL_INVESTIGATOR

SGS Belgium NV-Clinical Pharmacology Unit

Locations

SGS Belgium NV - Clinical Pharmacology Unit

Edegem, Antwerpen, Belgium

Countries

Belgium

Other Identifiers

CLI-05993AB8-01

Identifier Type: -

Identifier Source: org_study_id