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To evaluate the effects of oral administration rifampicin or itraconazole capsules on the pharmacokinetics of ASK120067 and its metabolite CCB4580030 in healthy subjects.
To evaluate the safety of ASK120067 tablets or combination with rifampicin capsules or itraconazole capsules in healthy subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| the effect of oral rifampicin on the pharmacokinetics of ASK120067 tablets | Experimental | Take ASK120067 tablets orally once on the first day at 160mg in fast condition;Take rifampicin capsules orally once on the days 8 to 17 at 600mg in fast condition, and a combination of 160mg ASK120067 and 600mg rifampicin were administrated on the 15th day in fast condition. |
|
| effect of oral itraconazole on the pharmacokinetics of ASK120067 tablets | Experimental | Take ASK120067 tablets orally once on the first day at 80mg in fast condition;Take itraconazole capsules orally twice on the days 8 to 13 at 200mg in fed condition, and a combination of 80mg ASK120067 and 200mg itraconazole were administrated on the 11th day in fast condition. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rifampicin; ASK120067 | Drug | Take ASK120067 tablets orally once on the first day at 160mg in fast condition;Take rifampicin capsules orally once on the days 8 to 17 at 600mg in fast condition, and a combination of 160mg ASk120067 and 600mg rifampicin were administrated on the 15th day in fast condition. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Collect plasma concentrations of ASK120067 and 1 metabolites following single dose at designated time points after the administration of ASK120067 in each period to figure out maximum concentration | Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose) |
| AUC | Collect plasma concentrations of ASK120067 and 1 metabolites following single dose at designated time points after the administration of ASK120067 in each period to figure out area under the plasma concentration-time curve | Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose) |
| Measure | Description | Time Frame |
|---|---|---|
| Tmax | Collect plasma concentrations of ASK120067 and 1 metabolites following single dose at designated time points after the administration of ASK120067 in each period to figure out time to reach maximum concentration | Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Juan Li | Drum Tower Hospital of Nanjing University School of Medical | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Drum Tower Hospital of Nanjing University School of Medical | Nanjing | Jiangsu | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37811634 | Derived | Cao B, Huang L, Liu M, Lin H, Ma T, Zhao Y, Geng Y, Yang Y, Guo H, Li J. Phase 1 study to evaluate the effects of rifampin or itraconazole on the pharmacokinetics of limertinib (ASK120067), a novel mutant-selective inhibitor of the epidermal growth factor receptor in healthy Chinese subjects. Expert Opin Drug Metab Toxicol. 2023 Sep;19(9):653-664. doi: 10.1080/17425255.2023.2260738. Epub 2023 Oct 12. |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| ASK120067;itraconazole | Drug | Take ASK120067 tablets orally once on the first day at 80mg in fast condition;Take itraconazole capsules orally twice on the days 8 to 13 at 200mg in fed condition, and a combination of 80mg ASK120067 and 200mg itraconazole were administrated on the 11th day in fast condition. |
|
| t1/2 | Blood samples will be collected from each subject at pre-specified times after the administration of ASK120067 in each period, (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose) | Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose) |
| CL/F | Collect plasma concentrations of ASK120067 and 1 metabolites following single dose at designated time points after the administration of ASK120067 in each period to figure out apparent clearance | Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose) |
| Vd/F | Collect plasma concentrations of ASK120067 and 1 metabolites following single dose at designated time points after the administration of ASK120067 in each period to figure out apparent volume of distribution | Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose) |
| λz | Collect plasma concentrations of ASK120067 and 1 metabolites following single dose at designated time points after the administration of ASK120067 in each period to figure out apparent terminal elimination rate constant | Blood samples will be collected from each subject after the administration of ASK120067 on Day 1 and Day 15 in arm A ,and on Day 1 and Day 11 in arm B (pre-dose, 0.25h,0.5h, 1h,1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 5h, 6h, 8h, 12h, 24h,36h,48h,72 h post dose) |
| Incidence and Severity of Treatment-Emergent Adverse Events | Assessed by number and severity of adverse events as recorded on the case report form | Adverse events will be collected from baseline until 18 days of arm A or 14 days of arm B after the first dose administration and the follow-up period |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |