Healthy Volunteers
Conditions
Keywords
pharmacokinetics, CHF10196, DDI, Dipeptidyl Peptidase 1 (DPP1) inhibitor
Brief summary
This Phase 1 study evaluates the effect of pantoprazole (a proton pump inhibitor) on the pharmacokinetics (PK) of CHF10196 (Florensocatib) in healthy male participants. Participants receive CHF10196 alone and in combination with pantoprazole to assess potential drug-drug interaction (DDI) effects on systemic exposure.
Interventions
DRUGCHF10196
Treatment Period 1: CHF10196 single dose administration on Day1; Treatment Period 2: CHF10196 single dose administration after pantoprazole single dose administration on Day13
DRUGPantoprazole
Treatment Period 2: Pantoprazole single dose administration from Day8 to Day13
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * BMI (body mass index) between 18.0 and 30.0 kg/m² * Weight between 45 and 100 kg * Non-smokers or ex-smokers (\<5 pack-years) * Clinically healthy based on medical history and examination * Normal vital signs * Normal ECG * Willingness to comply with contraception requirements Key
Exclusion criteria
* Recent participation in another clinical study * Significant medical conditions * Abnormal laboratory values * Positive HIV or hepatitis tests * Recent infection or COVID-19 * Drug or alcohol abuse * Use of prohibited medications * Gastrointestinal surgery affecting absorption * Hypersensitivity to study drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK parameter: AUC0-∞ | pre-dose up to 168 hours post-dose | comparing the ratio of adjusted geometric means for area under the concentration time curve from time 0 extrapolated to infinity (AUC0-∞) when CHF10196 administered alone and when administered with pantoprazole |
| PK parameter: AUC0-t | pre-dose up to 168 hours post-dose | comparing the ratio of adjusted geometric means for area under the plasma concentration time curve from time 0 to last quantifiable concentration (AUC0-t) when CHF10196 administered alone and when administered with pantoprazole |
| PK parameter: Cmax | pre-dose up to 168 hours post-dose | comparing the ratio of adjusted geometric means for maximum observed concentration when CHF10196 administered alone and when administered with pantoprazole |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability: Incidence of adverse events (AE) | From baseline (Day -1) to Day 8 for treatment period 1; from Day 8 to Day 20 for treatment period 2 | Number and percentage of adverse events (AE) when CHF10196 administered alone and when administered with pantoprazole |
| Safety and tolerability: Change from baselines for vital signs: PR | Day 1 to Day 7 for treatment period 1 and Day 8 to Day 19 for treatment period 2 | Mean changes from baselines to each post-dose timepoint in PR (pulse rate), by treatment period (TP). Baselines (the last value before the first administration of any CHF10196 of each TP or pantoprazole (TP2 only). In TP2, two separate baselines will be derived relative to pantoprazole and CHF10196) |
| Safety and tolerability: Change from baselines for vital signs - RR | Day 1 to Day 7 for treatment period 1 and Day 8 to Day 19 for treatment period 2 | Mean changes from baselines to each post-dose timepoint in vital signs: RR (respiratory rate) by treatment period (TP). Baselines (the last value before the first administration of any CHF10196 of each TP or pantoprazole (TP2 only). In TP2, two separate baselines will be derived relative to pantoprazole and CHF10196) |
| Safety and tolerability: Change from baselines for vital signs - blood pressure | Day 1 to Day 7 for treatment period 1 and Day 8 to Day 19 for treatment period 2 | Mean changes from baselines to each post-dose timepoint in vital signs (Systolic Blood Pressure and Diastolic Blood Pressure) by treatment period (TP). Baselines (the last value before the first administration of any CHF10196 of each TP or pantoprazole (TP2 only). In TP2, two separate baselines will be derived relative to pantoprazole and CHF10196) |
| Safety and tolerability: Change from baselines for ECG | Day 1 to Day 7 for treatment period 1 and Day 8 to Day 19 for treatment period 2 | change from baselines in milliseconds (ms). Intervals recorded: PR , RR, QT, QTc, QRS duration, QTcF (Fridericia-corrected QT interval Baselines (the last value before the first administration of any CHF10196 of each treatment period (TP) or pantoprazole (TP2 only). In TP2, two separate baselines will be derived relative to pantoprazole and CHF10196 |
| Safety and tolerability: Change from baseline for ECG (HR) | Day 1 to Day 7 for treatment period 1 and Day 8 to Day 19 for treatment period 2 | change from baseline for ECG recording of heart rate (HR) Baselines (the last value before the first administration of any CHF10196 of each Treatment Period (TP) or pantoprazole (TP2 only). In TP2, two separate baselines will be derived relative to pantoprazole and CHF10196). |
| Safety and tolerability: Change from baseline for laboratory abnormalities | From baseline (Day -1) to Day 8 for treatment period 1; from Day 8 to Day 20 for treatment period 2 | Number of participants with abnormal blood laboratory test results. Quantitative laboratory parameters (chemistry and haematology) will be summarised by treatment as absolute value and change from baseline using descriptive statistics |
| Additional pharmacokinetic parameters: AUC0-24h | From Day 1 to Day 2 for treatment period 1; from Day 13 to Day 14 for treatment period 2 | comparing the ratio of adjusted geometric means for the area under the plasma concentration time curve from time 0 to 24 h post-dose when CHF10196 administered alone and when administered with pantoprazole (with their 90% two-sided Confidence Intervals) |
| Additional pharmacokinetic parameters: CL/F | From baseline (Day -1) to Day 8 for treatment period 1; from Day 8 to Day 20 for treatment period 2 | comparing the total body clearance (CL/F) by treatment period using descriptive statistics |
| Additional pharmacokinetic parameters: t1/2 | From baseline (Day -1) to Day 8 for treatment period 1; from Day 8 to Day 20 for treatment period 2 | comparing the terminal half-life (t1/2) by treatment period using descriptive statistics |
| Additional pharmacokinetic parameters: Vd/F | From baseline (Day -1) to Day 8 for treatment period 1; from Day 8 to Day 20 for treatment period 2 | comparing the apparent volume of distribution (Vd/F) by treatment period using descriptive statistics |
| Additional pharmacokinetic parameters: tmax | From baseline (Day -1) to Day 8 for treatment period 1; from Day 8 to Day 20 for treatment period 2 | Evaluating the Hodges-Lehmann non-parametric estimate of location shift between CHF10196 with pantoprazole (test) and CHF10196 alone (reference) in median time corresponding to maximum plasma when CHF10196 administered alone and when administered with pantoprazole concentration (tmax) |
Countries
United Kingdom
Contacts
CONTACTChiesi Clinical trial Info
PRINCIPAL_INVESTIGATORBenjamen Monaghan
Fortrea Clinical Research Unit (CRU)
Outcome results
None listed