Clinical Pharmacology Study to Evaluate the Total Systemic Exposure and the Lung Availability of CHF 5993, Administered Via the Multi-dose Reservoir NEXThaler® Dry Powder Inhaler and Via a HFA-pressurised Metered Dose Inhaler With and Without Valved Holding Chamber, in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- CHF 5993 100/6/12,5 pMDI with Valved Holding Chamber
- Conditions
- COPD
- Sponsor
- Chiesi Farmaceutici S.p.A.
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Evaluation of the Area under the curve (AUC) for the lung exposure of B17MP (active metabolite of Beclometasone Dipropionate), Formoterol and Glycopirronium Bromide after charcoal blockage.
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This clinical pharmacology study is performed to evaluate the total systemic exposure and the lung availability of CHF 5993 DPI and pMDI with and without valved holding chamber, in healthy volunteers.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject's written informed consent obtained prior to any study related procedure.
- •Ability to understand the study procedures, the risks involved, and ability to be trained to use the pMDI device correctly with AIM™ (Aerosol Inhalation Monitor) Vitalograph®.
- •Ability to generate sufficient PIF (at least 40 L/min) using the In-Check device simulating NEXThaler® device.
- •Male and female Caucasian subjects aged 18 to 55 years inclusive.
- •Body mass index (BMI) within the range of 18 to 30 kg/m2 inclusive.
- •Non-smokers or ex-smokers who smoked \< 5 pack years (pack-years = the number of cigarette packs per day, times the number of years) and stopped smoking \> 1 year prior to screening.
- •Good physical and mental status, determined on the basis of the medical history and a general clinical examination, at screening and before randomization.
- •Lung function measurements within normal limits (Normal values: FEV1/FVC is \> 0.70 and FEV1 \> 80% predicted).
- •Female subject of non-childbearing potential (WONCBP) defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile) and female subjects of childbearing potential (WOCBP) fulfilling one of the following criteria:
- •WOCBP with fertile male partners: they and/or their partner of childbearing potential must be willing to use a double barrier contraceptive method including one highly effective birth control method and one acceptable birth control method (male or female condom with or without spermicide and/or cap, diaphragm or sponge with spermicide), from the signature of the informed consent and until 3 months after follow-up visit;
Exclusion Criteria
- •Blood donation (equal or more than 450 ml) or blood loss, less than 8 weeks prior screening or prior randomization.
- •Abnormal haemoglobin level defined as \< 10.5 g/dl
- •For females only: pregnant and lactating female subjects, confirmed by a positive serum test at screening and/or urine test before randomization.
- •Positive HIV1 or HIV2 serology.
- •Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C.
- •Unsuitable veins for repeated venipuncture.
- •Documented history of alcohol abuse within 12 months prior to screening.
- •Documented history of drug abuse within 12 months prior to screening, or positive urine drug test performed at screening and/or before randomization.
- •Subjects who have a positive urine test for cotinine at screening and/or before randomization.
- •Clinically relevant abnormal laboratory values, suggesting an unknown disease and requiring further clinical investigation.
Arms & Interventions
CHF 5993 100/6/12,5 pMDI VHC
with/without Charcoal Block with Valved Holding Chamber
Intervention: CHF 5993 100/6/12,5 pMDI with Valved Holding Chamber
CHF 5993 100/6/12,5 pMDI (replicate)
with/without Charcoal Block
Intervention: CHF 5993 100/6/12,5 pMDI replicate
CHF 5993 100/6/12,5 pMDI
with/without Charcoal Block
Intervention: CHF 5993 100/6/12,5 pMDI
CHF 5993 100/6/12,5 DPI test 1
with/without Charcoal Block
Intervention: CHF 5993 100/6/12,5 DPI Test 1
CHF 5993 100/6/12,5 DPI test 2
with/without Charcoal Block
Intervention: CHF 5993 100/6/12,5 DPI Test 2
Outcomes
Primary Outcomes
Evaluation of the Area under the curve (AUC) for the lung exposure of B17MP (active metabolite of Beclometasone Dipropionate), Formoterol and Glycopirronium Bromide after charcoal blockage.
Time Frame: 72 hours after adminstration
AUC 0-t
Evaluation of the Maximum Plasma Concentration (Cmax) for the systemic exposure of B17MP (active metabolite of Beclometasone Dipropionate), Formoterol and Glycopirronium Bromide.
Time Frame: 72 hours after adminstration
Cmax
Evaluation of the area under the curve (AUC0-t) for the systemic exposure of B17MP (active metabolite of Beclometasone Dipropionate), Formoterol and Glycopirronium Bromide.
Time Frame: 72 hours after adminstration
AUC0-t
Evaluation of the Maximum Plasma Concentration (Cmax) for the lung exposure of B17MP (active metabolite of Beclometasone Dipropionate), Formoterol and Glycopirronium Bromide after charcoal blockage.
Time Frame: 72 hours after adminstration
Cmax
Secondary Outcomes
- Evaluate the Area Under the Curve of Beclometasone Dipropionate, B17MP (active metabolite of Beclometasone Dipropionate), formoterol and Glycopirronium bromide with and without charcoal blockage(72 hours after adminstration)
- Evaluate the number of Adverse events and adverse drug reactions(72 hours after adminstration)
- Evaluation of the heart rate(72 hours after adminstration)
- Evaluate the Maximum Plasma Concentration of Beclometasone Dipropionate, B17MP (active metabolite of Beclometasone Dipropionate), formoterol and Glycopirronium bromide with and without charcoal blockage(72 hours after adminstration)
- Evaluation of Blood pressure(72 hours after adminstration)