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®

Chiesi

Status and phase: Completed; Phase 1

Conditions: Asthma

Treatments: Drug: Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg); Drug: Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI; Drug: Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI

Study type: Interventional

Funder types: Industry

Identifiers

NCT05898984

CLI-05993AB8-01

Details and patient eligibility

About

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.

Full 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).

Enrollment: 69 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Other Inclusion/exclusion criteria as defined by the protocol.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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69 participants in 3 patient groups

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

Experimental group

Description:

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.

Treatment:

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 group

Description:

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.

Treatment:

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 group

Description:

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).

Treatment:

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