AsthmaPhase 1NCT05898984
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®
A Phase 1 study testing Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI, Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI and Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg) in people with Asthma, run by Chiesi Farmaceutici S.p.A. at 1 site in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI, Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI and Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 1 siteBelgium
- Study dates
- 24 Apr 2023to 14 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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 locations and contacts
1 site in 1 country.
Belgium1 site
SGS Belgium NV - Clinical Pharmacology Unit
Edegem, Antwerpen, 2650
About this study
Official title: A Single Dose, Randomized, Open-label, 3-Way Cross-over Clinical Pharmacology Study, to Evaluate the Systemic Exposure of BDP, Beclomethasone 17-monoproprionate, Formoterol Fumarate, and Glycopyrronium Bromide, After Inhalation of the Fixed Combination BDP/FF/GB HFA pMDI (CHF 5993) at Two Different Strengths and of BDP Hydrofluoroalkane (HFA), in Healthy Volunteers.
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.
Read the 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:
- 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);
- 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).
- 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
- Being tested
- Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI, Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI, Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg)
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDIDrug
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).
Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDIDrug
Also called Trimbow Medium Strenght (MS)®
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)Drug
Also called QVAR REDIHALER®
pressurised, breath-actuated, metered dose aerosol with a dose counter): 8 inhalations (TDD of BDP: 640 µg ex-actuator, 800 µg ex valve).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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). Receives: Drug: Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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.
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 area under the concentration-time curve from zero to infinity (AUC0-∞) 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);
Measured: 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.
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 Time to Cmax (t max) 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);
Measured: 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.
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 Time to t1/2 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);
Measured: 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
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 Area under the concentration time curve from zero to time 't' where t is the last quantifiable time point (AUC0-t) 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);
Measured: 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
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI:
To Time to Cmax (t max) 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);
Measured: From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB
t max of BDP across two different dose strengths of CHF 5993
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 tmax 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);
Measured: 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 after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg)
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. BDP HFA (QVAR REDIHALER®, BDP 80 µg):
To compare the systemic exposure to BDP as Area under the concentration time curve from zero to time 't' where t is the last quantifiable time point (AUC0-t) for B17MP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Measured: From pre-dose to 24 hours post dose
Area under the concentration time curve from zero to time 't' where t is the last quantifiable time point (AUC0-t) of B17MP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. BDP HFA (QVAR REDIHALER®, BDP 80 µg):
To compare the systemic exposure to B17MP as Area under the concentration time curve from zero to time 't' where t is the last quantifiable time point (AUC0-t) for B17MP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Measured: From pre-dose to 24 hours post dose
maximum plasma concentration (Cmax) of BDP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. BDP HFA (QVAR REDIHALER®, BDP 80 µg):
To compare the systemic exposure to BDP as maximum plasma concentration (Cmax) for B17MP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Measured: From pre-dose to 24 hours post dose
maximum plasma concentration (Cmax) of B17MPafter a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. BDP HFA (QVAR REDIHALER®, BDP 80 µg):
To compare the systemic exposure to B17MP as maximum plasma concentration (Cmax) for B17MP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Measured: From pre-dose to 24 hours post dose
t max of BDP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. BDP HFA (QVAR REDIHALER®, BDP 80 µg):
To compare the systemic exposure to BDP as t max after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Measured: From pre-dose to 24 hours post dose
t max of BDP of B17MPafter a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. BDP HFA (QVAR REDIHALER®, BDP 80 µg):
To compare the systemic exposure to B17MP as t max after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Measured: From pre-dose to 24 hours post dose
Area under the concentration-time curve from zero to infinity (AUC0-∞) of B17MPafter a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. BDP HFA (QVAR REDIHALER®, BDP 80 µg):
To compare the systemic exposure to B17MP as Area under the concentration-time curve from zero to infinity (AUC0-∞) after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Measured: From pre-dose to 24 hours post dose
Time to t1/2 of B17MPafter a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI vs. BDP HFA (QVAR REDIHALER®, BDP 80 µg):
To compare the systemic exposure to B17MP as Time to t1/2 of B17MP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Measured: From pre-dose to 24 hours post dose
Incidence of Adverse events
Number and percentage of subject with at least one event and number of treatment-emergent events.
Measured: through study completion, an average of 90 days, screening phase inclusive
Incidence of study drugs reactions
Number and percentage of subject with at least one event and number of treatment-emergent events.
Measured: through study completion, an average of 90 days, screening phase inclusive
Change of systolic and diastolic Blood pressure
The number and percentage of subjects with QTcF in the following intervals will be presented at each post-dose time point and at any post-dose time point by treatment:
- Change from pre-dose >20 mmHg for SBP; Change from pre-dose >10 mmHg for DBP.
Measured: from pre-dose to 24hours post dose
12-lead ECG
The number and percentage of subjects with abnormal actual QTcF (Fridericia-correctedQT Interval).
Measured: From Pre-dose to 75 minutes post dose
12-lead ECG
The number and percentage of subjects with abnormal change from the baseline of QTcF
Measured: From Pre-dose to 75 minutes post dose
Number of participants with abnormal laboratory test results
Clinical chemistry,Fasting serum glucose;Haematology parameters will be evaluated. For continuous laboratory parameters, the laboratory values and the change from baseline will be summarised at each visit by treatment sequence using descriptive statistics. For categorical laboratory parameters, a frequency table of results will be produced at each visit by treatment sequence.
Measured: through study completion, an average of 90 days, screening phase inclusive
body temperature abnormal values
For continuous laboratory parameters, the laboratory values and the change from baseline will be summarised at each visit by treatment sequence using descriptive statistics.
Measured: through study completion, an average of 90 days, screening phase inclusive
Number of participants with abnormal results of physical examinations
For continuous laboratory parameters, the laboratory values and the change from baseline will be summarised at each visit by treatment sequence using descriptive statistics.
Measured: through study completion, an average of 90 days, screening phase inclusive
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start24 Apr 2023
- Primary completion14 Jul 2023
- Study completion14 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SGS S.A.
- Responsible party
- Sponsor
- Investigators
- Jelle Klein, MD, Principal investigator, SGS Belgium NV-Clinical Pharmacology Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05898984
- Sponsor's protocol ID
- CLI-05993AB8-01
- Status last verified
- Oct 2024
- First submitted
- 14 Apr 2023
- Last updated
- 31 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Dose, Randomized, Open-label, 3-Way Cross-over Clinical Pharmacology Study, to Evaluate the Systemic Exposure of BDP, Beclomethasone 17-monoproprionate, Formoterol Fumarate, and Glycopyrronium Bromide, After Inhalation of the Fixed Combination BDP/FF/GB HFA pMDI (CHF 5993) at Two Different Strengths and of BDP Hydrofluoroalkane (HFA), in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT05898984
- Acronym / sponsor ID
- CLI-05993AB8-01
- Conditions
- Asthma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- SGS S.A.
- Study start
- 24 Apr 2023 (actual)
- Primary completion
- 14 Jul 2023 (actual)
- Study completion
- 14 Jul 2023 (actual)
- First posted
- 12 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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);
- 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).
- 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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| single dose of CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI (T) | Experimental | Drug: Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDICHF 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. |
| single dose of CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI (R1) | Active comparator | Drug: Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDICHF 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. |
| Single dose of BDP HFA (QVAR REDIHALER®, BDP 80 μg) (R2) | Active comparator | Drug: Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg)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). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDICHF 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). | Drug | 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 pMDIAlso: Trimbow Medium Strenght (MS)®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 | Drug | 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)Also: QVAR REDIHALER®pressurised, breath-actuated, metered dose aerosol with a dose counter): 8 inhalations (TDD of BDP: 640 µg ex-actuator, 800 µg ex valve). | Drug | Single dose of BDP HFA (QVAR REDIHALER®, BDP 80 μg) (R2) |
Primary outcome
systemic exposure ( area under the concentration time curve from zero to time) to beclomethasone 17 monopropionate (B17MP), FF and GB
Time frame: From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for 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).
systemic exposure (maximum plasma concentration (Cmax) ) to beclomethasone 17 monopropionate (B17MP), FF and GB
Time frame: From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for 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).
22 secondary outcomes
Area under the concentration-time curve from zero to infinity (AUC0-∞) of B17MP, FF and GB across two different dose strengths of CHF 5993.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB
t max of BDP across two different dose strengths of CHF 5993
Time frame: 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 after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg)
Time frame: From pre-dose to 24 hours post dose
Area under the concentration time curve from zero to time 't' where t is the last quantifiable time point (AUC0-t) of B17MP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Time frame: From pre-dose to 24 hours post dose
maximum plasma concentration (Cmax) of BDP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Time frame: From pre-dose to 24 hours post dose
maximum plasma concentration (Cmax) of B17MPafter a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Time frame: From pre-dose to 24 hours post dose
t max of BDP after a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Time frame: From pre-dose to 24 hours post dose
t max of BDP of B17MPafter a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Time frame: From pre-dose to 24 hours post dose
Area under the concentration-time curve from zero to infinity (AUC0-∞) of B17MPafter a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Time frame: From pre-dose to 24 hours post dose
Time to t1/2 of B17MPafter a single inhaled dose of CHF 5993 BDP/FF/GB 200/6/12.5 μg and of BDP HFA (QVAR REDIHALER®, BDP 80 μg);
Time frame: From pre-dose to 24 hours post dose
Incidence of Adverse events
Time frame: through study completion, an average of 90 days, screening phase inclusive
Incidence of study drugs reactions
Time frame: through study completion, an average of 90 days, screening phase inclusive
Change of systolic and diastolic Blood pressure
Time frame: from pre-dose to 24hours post dose
12-lead ECG
Time frame: From Pre-dose to 75 minutes post dose
12-lead ECG
Time frame: From Pre-dose to 75 minutes post dose
Number of participants with abnormal laboratory test results
Time frame: through study completion, an average of 90 days, screening phase inclusive
body temperature abnormal values
Time frame: through study completion, an average of 90 days, screening phase inclusive
Number of participants with abnormal results of physical examinations
Time frame: through study completion, an average of 90 days, screening phase inclusive
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jelle Klein, MD principal investigator
SGS Belgium NV-Clinical Pharmacology Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Test product (T):CHF 5993 BDP/FF/GB 200/6/12.5 µg pMDI, Reference product 1 (R1): CHF 5993 BDP/FF/GB 100/6/12.5 µg pMDI and Reference product 2 (R2): BDP HFA (QVAR REDIHALER®, BDP 80 μg) in people with Asthma, run by Chiesi Farmaceutici S.p.A. at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
systemic exposure ( area under the concentration time curve from zero to time) to beclomethasone 17 monopropionate (B17MP), FF and GB (time frame: From pre-dose to 24 hours post dose for BDP/B17MP and from pre-dose to 72hours post dose for FF and GB). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2024.