Healthy Male Volunteers
Conditions
Keywords
pharmacokinetics, CHF10196, DDI, Dipeptidyl Peptidase 1 (DPP1) inhibitor
Brief summary
The purpose of this study is to assess the potential drug-drug interaction of CHF10196 (a dipeptidyl peptidase 1 inhibitor) and its metabolite on the pharmacokinetics of dabigatran (a P-glycoprotein substrate) and Rosuvastatin (a breast cancer resistant protein substrate) in healthy male participants.
Interventions
DRUGCHF10196
Treatment period 2: Single dose administered daily from Day 8 to Day 19
DRUGDabigatran Etexilate
Treatment period 1: Single dose administered on Day 1; Treatment period 2: Single dose administered on Day 13
DRUGRosuvastatin
Treatment period 1: Single dose administered on Day 4; Treatment period 2: Single dose administered on Day 16
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will receive dabigatran and rosuvastatin alone and in combination with CHF10196 at steady-state in two sequential treatment periods.
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male participants aged 18 to 55 years * Body mass index between 18.0 and 30.0 kg/m² * Non-smokers or ex-smokers (\<5 pack-years) * Clinically healthy based on medical history and examination * Vital signs and ECG within normal limits * Willing and able to comply with study procedures
Exclusion criteria
* Use of prohibited concomitant medications * Participation in another clinical study within 3 months * Clinically relevant medical conditions * Abnormal laboratory values * Positive HIV, hepatitis B, or hepatitis C * History of bleeding disorders * Drug or alcohol abuse * Use of nicotine-containing products within defined period * Recent COVID-19 infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Dabigatran : AUC0-t | Up to 72 hours after dosing | comparing the ratios of adjusted geometric means between test 1 (dabigatran \[free and total\] with CHF10196) and reference 1 (dabigatran \[free and total\] alone), with 90% two-sided Confidential Intervals(CI), will be calculated for plasma dabigatran (free and total) area under the plasma concentration-time curve, from time 0 to the last measurable concentration (AUC0-t) |
| Pharmacokinetics of Dabigatran: AUC0-∞ | Up to 72 hours after dosing | comparing the ratios of adjusted geometric means between test 1 (dabigatran \[free and total\] with CHF10196) and reference 1 (dabigatran \[free and total\] alone), with 90% two-sided CIs, will be calculated for plasma dabigatran (free and total) area under the plasma concentration-time curve, from time 0 to the last measurable concentration (AUC0-∞) |
| Pharmacokinetics of Dabigatran: Cmax | Up to 72 hours after dosing | comparing the ratios of adjusted geometric means between test 1 (dabigatran \[free and total\] with CHF10196) and reference 1 (dabigatran \[free and total\] alone), with 90% two-sided CIs, will be calculated for plasma dabigatran (free and total) maximum observed maximum observed concentration (Cmax) |
| Pharmacokinetics of Rosuvastatin :AUC0-t | Up to 96 hours after dosing | The ratios of adjusted geometric means between test 2 (rosuvastatin with CHF10196) and reference 2 (rosuvastatin alone), with 90% two sided CIs, will be calculated for plasma rosuvastatin AUC0-t |
| Pharmacokinetics of Rosuvastatin : AUC0-∞ | Up to 96 hours after dosing | The ratios of adjusted geometric means between test 2 (rosuvastatin with CHF10196) and reference 2 (rosuvastatin alone), with 90% two sided CIs, will be calculated for plasma rosuvastatin (AUC0-∞) |
| Pharmacokinetics of Rosuvastatin: Cmax | Up to 96 hours after dosing | The ratios of adjusted geometric means between test 2 (rosuvastatin with CHF10196) and reference 2 (rosuvastatin alone), with 90% two sided CIs, will be calculated for plasma rosuvastatin Cmax |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability : Incidence of adverse events (AE) | From Baseline Day -1 until Day 8 of TP1 and from Day 8 to Day 20 of TP2 | Number and percentage of study participants by treatment with AEs, adverse events of special interest(AESIs),treatment emergent adverse event(TEAEs), adverse drug reaction(ADRs), non-serious TEAEs, serious TEAEs, serious ADRs, severe TEAEs, TEAEs leading to study discontinuation and to death |
| Safety and Tolerability : change from baseline for laboratory abnormalities | From Baseline Day -1 until Day 8 for TP1, and from Day 8 to Day 20 of TP 2 | Clinical laboratory abnormalities, based on haematology and blood chemistry test results by treatment period (TP). 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 |
| Safety and Tolerability: changes from baseline for vital signs - pulse rate | From Day 1 to Day 8 for TP1 and from Day 8 to Day 20 for TP2 | Mean changes from baseline to each post-dose timepoint in vital signs PR (pulse rate) by TP Baselines (the last value before the first administration of dabigatran etexilate of each TP or CHF10196 (TP2 only). In TP2, two separate baselines will be derived relative to dabigatran and CHF10196) |
| Safety and Tolerability: changes from baseline for vital signs - respiratory rate | From Day 1 to Day 8 for TP1 and from Day 8 to Day 20 for TP2 | Mean changes from baseline to each post-dose timepoint in vital signs RR (respiratory rate) by TP Baselines (the last value before the first administration of dabigatran etexilate of each TP or CHF10196 (TP2 only). In TP2, two separate baselines will be derived relative to dabigatran and CHF10196) |
| Safety and Tolerability: changes from baseline for vital signs - blood pressure | From Day 1 to Day 8 for TP1 and from Day 8 to Day 20 for TP2 | Mean changes from baseline to each post-dose timepoint in vital signs systolic blood pressure (SBP) and diastolic blood pressure (DBP) by TP. Baselines (the last value before the first administration of dabigatran etexilate of each TP or CHF10196 (TP2 only). In TP2, two separate baselines will be derived relative to dabigatran and CHF10196) |
| Safety and Tolerability : change from baseline for ECG intervals | From Day 1 to Day 8 for TP1 and from Day 8 to Day 20 for TP2 | Mean changes from baseline to each post-dose timepoint in 12-lead bedside ECG parameters. Intervals recorded: RR, PR, QT, QTc (Corrected QT interval), and QTcF (Fridericia corrected QT interval), and QRS duration by TP. Baselines (the last value before the first administration of dabigatran etexilate of each TP or CHF10196 (TP2 only). In TP2, two separate baselines will be derived relative to dabigatran and CHF10196) |
| Safety and Tolerability : change from baseline for ECG HR | From Day 1 to Day 8 for TP1 and from Day 8 to Day 20 for TP2 | Mean changes from baseline to each post-dose timepoint in 12-lead bedside ECG recording of Heart Rate (HR). Baselines (the last value before the first administration of dabigatran etexilate of each TP or CHF10196 (TP2 only). In TP2, two separate baselines will be derived relative to dabigatran and CHF10196) |
| Additional Pharmacokinetic Parameters : CL/F of dabigatran | From Day 1 to Day 4 for TP1 and from Day 13 to Day 16 for TP2 | total body clearance (CL/F) of dabigatran (free and total) will be analysed with descriptive statistics by TP |
| Additional Pharmacokinetic Parameters: CL/F of resuvastatin | From Day 4 to Day 8 for TP1 and from Day 16 to Day 20 for TP2 | total body clearance (CL/F) of rosuvastatin will be analysed with descriptive statistics by TP |
| Additional Pharmacokinetic Parameters: Vd/F of dabigatran | From Day 1 to Day 4 for TP1 and from Day 13 to Day 16 for TP2 | Apparent volume of distribution (Vd/F) of dabigatran (free and total) will be analysed with descriptive statistics by TP |
| Additional Pharmacokinetic Parameters: Vd/F of rosuvastatin | From Day 4 to Day 8 for TP1 and from Day 16 to Day 20 forTP2 | Apparent volume of distribution (Vd/F) of rosuvastatin will be analysed with descriptive statistics by TP |
| Additional Pharmacokinetic Parameters: tmax of dabigatran | From Day 1 to Day 4 for TP1 and from Day 13 to Day 16 for TP2 | Difference in median plasma tmax of dabigatran (free and total) between test 1 (dabigatran \[free and total\] with CHF10196) and reference 1 (dabigatran \[free and total\] alone) with 90% two-sided CIs |
| Additional Pharmacokinetic Parameters: tmax of rosuvastatin | From Day 4 to Day 8 for TP1 and from Day 16 to Day 20 for TP2 | Difference in median plasma tmax of rosuvastatin between test 2 (rosuvastatin with CHF10196) and reference 2 (rosuvastatin alone) with 90% two-sided CIs |
Countries
United Kingdom
Contacts
CONTACTChiesi Clinical Trial Info
PRINCIPAL_INVESTIGATORJonathan Ackroyd
Fortrea Clinical Research Unit (CRU)
Outcome results
None listed