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This is a an open-label, fixed-sequence DDI study conducted in Chinese healthy subjects to investigate the effect of multiple oral doses of pimicotinib on the pharmacokinetics of fexofenadine , rosuvastatin and metformin . Fexofenadine and rosuvastatin will be administered together as a cocktail, and metformin will be given via staggered dosing from the cocktail drugs administration.
Approximately 38 healthy subjects will be enrolled to achieve 28 evaluable healthy subjects complete the study.
Blood samples will be collected for PK analysis .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pimicotinib with Metformin, Fexofenadine and Rosuvastatin | Other | Multiple oral doses of pimicotinib (50 mg QD) on the pharmacokinetics of fexofenadine (P-gp sensitive substrate), rosuvastatin (BCRP sensitive substrate) and metformin (MATE1 sensitive substrate). Fexofenadine and rosuvastatin will be administered together as a cocktail, and metformin will be given via staggered dosing from the cocktail drugs administration.All subjects will receive the following study interventions:Day 1: metformin, Day 3: cocktail, Day 8 to 13: pimicotinib once daily (QD), Day 14: metformin + pimicotinib, Day 15: pimicotinib, Day 16: cocktail + pimicotinib, Day 17 to 20: pimicotinib QD |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| pimicotinib capsules | Drug | the effect of multiple oral doses of pimicotinib (50 mg QD) on the pharmacokinetics of fexofenadine (P-gp sensitive substrate), rosuvastatin (BCRP sensitive substrate) and metformin (MATE1 sensitive substrate). Fexofenadine and rosuvastatin will be administered together as a cocktail, and metformin will be given via staggered dosing from the cocktail drugs administration |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Peak concentration, the maximum observed plasma concentration of metformin, fexofenadine and rosuvastatin | pre-dose, post-dose 0.5 hour, 1 hour, 1.5hours,2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours |
| AUClast | Area under the plasma concentration-time curve from time 0 to the time of last measurable concentration | pre-dose, post-dose 0.5 hour, 1 hour, 1.5hours,2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours |
| AUC0-∞ | Area under the plasma concentration-time curve from time 0 to infinity | pre-dose, post-dose 0.5 hour, 1 hour, 1.5hours,2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours |
| Measure | Description | Time Frame |
|---|---|---|
| AE | Safety profile of pimicotinib in combination with metformin, fexofenadine and rosuvastatin including but not limited to Adverse events (AEs), | through study completion, an average of 50 days |
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Inclusion Criteria:
Healthy subjects aged 18 to 50 years (inclusive) at screening and at least 25% of each sex should be included.
Weight ≥ 50.0 kg (male) or ≥ 45.0 kg (female), with a body mass index (BMI) between 18.0 and 28.0 (inclusive), BMI = weight (kg)/height (m)2;
Normal or abnormal but not clinically significant results in physical examination, clinical laboratory tests and other relevant examinations as assessed by the investigator at Screening;
Male or female subjects of childbearing potential must agree to use effective methods of contraception during the study and within 6 months after the last dose of investigational product, and male subjects should not donate sperm during such period; female subjects should not donate ovum during such period and should not be pregnant or lactating. Pregnancy period is defined as the period from the date of conception until termination of pregnancy, and will be determined by laboratory test of human chorionic gonadotropin (hCG) during medical examination and baseline prior to initiation of the study;
Willing to participate in this study, understand the study procedures and sign the informed consent form prior to screening; willing to comply with the study procedures.
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wei Zhao, Doctor | The First Affiliated Hospital Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) | Jinan | Shandong | 250014 | China |
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Fexofenadine and rosuvastatin will be administered together as a cocktail, and metformin will be given via staggered dosing from the cocktail drugs administration. All subjects will receive the following study interventions:Day 1: metformin; Day 3: cocktail;Day 8 to 13: pimicotinib once daily (QD);Day 14: metformin + pimicotinib;Day 15: pimicotinib,Day 16: cocktail + pimicotinib,Day 17 to 20: pimicotinib QD
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