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®

NCT05898984 | Completed Phase 1

• 1 other identifier: CLI-05993AB8-01
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• systemic exposure ( area under the concentration time curve from zero to time) to beclomethasone 17 monopropionate (B17MP), FF and GB

  CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI: To evaluate the systemic exposure to beclomethasone 17 monopropionate (B17MP), FF and GB as area under the concentration time curve from zero to time 't' where t is the last quantifiable time point (AUC0-t) across two different dose strengths of CHF 5993 BDP/FF/GB (200/6/12.5 μg and 100/6/12.5 μg).

  From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB

• systemic exposure (maximum plasma concentration (Cmax) ) to beclomethasone 17 monopropionate (B17MP), FF and GB

  CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI: To evaluate the systemic exposure to beclomethasone 17 monopropionate (B17MP), FF and GB as 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).

  From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB

Secondary Outcomes (22)

• Area under the concentration-time curve from zero to infinity (AUC0-∞) of B17MP, FF and GB across two different dose strengths of CHF 5993.

  From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB

• Time to Cmax (t max) of B17MP, FF and GB across two different dose strengths of CHF 5993.

  From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB

• Time to t1/2 of B17MP, FF and GB across two different dose strengths of CHF 5993.

  From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB

• Area under the concentration time curve from zero to time 't' where t is the last quantifiable time point (AUC0-t) of BDP across two different dose strengths of CHF 5993

  From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB

• Time to Cmax (t max) of BDP across two different dose strengths of CHF 5993

  From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB

Study Arms (3)

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

EXPERIMENTAL

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.

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

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

ACTIVE COMPARATOR

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.

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

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

ACTIVE COMPARATOR

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).

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

Interventions

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

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

Also known as: Trimbow Medium Strenght (MS)®

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

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

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

Also known as: QVAR REDIHALER®

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

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: At least 28 subjects will be males and at least 28 subjects will be females, to ensure gender representation.
• 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 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead
• SGS S.A.: collaborator

Study Sites (1)

SGS Belgium NV - Clinical Pharmacology Unit

Edegem, Antwerpen, 2650, Belgium

Location

MeSH Terms

Conditions

Asthma

Interventions

alpha-ketoisovalerate dehydrogenase phosphatase

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Jelle Klein, MD

  SGS Belgium NV-Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The doses will be administered to all subjects in a crossover design. The doses administered as a single dose for the Test product (T: CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI) and Reference product 1 (R1: CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI) in this study are equivalent to the TDD authorised for asthma and the maximum TDD authorized for Reference product 2 (R2: BDP HFA \[QVAR REDIHALER®, BDP 80 μg\]) in regular treatment of asthma.

Study Record Dates

• First Submitted: April 14, 2023
• First Posted: June 12, 2023
• Study Start: April 24, 2023
• Primary Completion: July 14, 2023
• Study Completion: July 14, 2023
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)