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| Name | Class |
|---|---|
| SGS S.A. | INDUSTRY |
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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.
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:
Participation in the study will last for a maximum of 70 days for each subject (starting from randomization).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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); |
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Inclusion Criteria:
Exclusion Criteria:
Other Inclusion/exclusion criteria as defined by the protocol.
At least 28 subjects will be males and at least 28 subjects will be females, to ensure gender representation.
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| Name | Affiliation | Role |
|---|---|---|
| Jelle Klein, MD | SGS Belgium NV-Clinical Pharmacology Unit | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| SGS Belgium NV - Clinical Pharmacology Unit | Edegem | Antwerpen | 2650 | Belgium |
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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.
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| 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 |
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| 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). |
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| 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); | 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); | 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); | 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); | 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); | 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); | 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); | 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); | 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); | 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); | 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); | 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); | 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); | 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. | 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. | 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. | from pre-dose to 24hours post dose |
| 12-lead ECG | The number and percentage of subjects with abnormal actual QTcF (Fridericia-correctedQT Interval). | 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 | 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. | 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. | 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. | through study completion, an average of 90 days, screening phase inclusive |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C048053 | alpha-ketoisovalerate dehydrogenase phosphatase |
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