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To assess the pharmacokinetics of TY-9591 tablets and Osimertinib Mesylate tablets after a single fasting administration and the effect of food on the pharmacokinetics of TY-9591 tablets in healthy volunteers.
This is a single center, randomized, open label, two phases study in healthy adult volunteers. The first phase is a two-sequence, two-period crossover trial. The volunteers will be randomly distributed into two groups and given either TY-9591 tablets or Osimertinib Mesylate tablets on a single fasting administration. In the second phase, all volunteers will be administrated TY-9591 tablets after a high fat meal. The washout between each treatment is no less than 21 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm1: TY-9591 + Osimertinib + TY-9591 | Experimental | Participants will receive TY-9591 tablets under fasted condition in period 1 , followed by Osimeritinib Mesylate tablet under fasted condition in period 2. In period 3, participants will receive TY-9591 tablet in fed state (high-fat meal). The washout will be no less than 21 days between each treatment. |
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| Arm2: Osimertinib + TY-9591 + TY-9591 | Experimental | Participants will receive Osimeritinib Mesylate tablet under fasted condition in period 1 , followed by TY-9591 tablets under fasted condition in period 2. In period 3, participants will receive TY-9591 tablet in fed state (high-fat meal). The washout will be no less than 21 days between each treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TY-9591 Tablets under Fasted Condition - Arm1 | Drug | Phase 1 (period 1) fasted from 10 hours prior to dosing with 80 mg TY-9591 tablet (p o, once) and 4 hours after dosing on day 1. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of TY-9591 and its metabolites | Pharmacokinetics of TY-9591 and its metabolites (TY-9591-D1 (AZ5104) and TY-9591-D2) by assessment of the maximum plasma concentration. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| Cmax of Osimertinib and its metabolites | Pharmacokinetics of Osimertinib and its metabolites (AZ5104 and AZ7550) by assessment of the maximum plasma concentration. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| AUC(0-72h) of TY-9591 and its metabolites | Pharmacokinetics of TY-9591 and its metabolites (TY-9591-D1 (AZ5104) and TY-9591-D2) by assessment of area under the plasma concentration time curve from zero to 72 hours. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| AUC(0-72h) of Osimertinib and its metabolites | Pharmacokinetics of Osimertinib and its metabolites (AZ5104 and AZ7550) by assessment of area under the plasma concentration time curve from zero to 72 hours. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Tmax of TY-9591 and its metabolites | Pharmacokinetics of TY-9591 and its metabolites by assessment of time to Cmax. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| Tmax of Osimertinib and its metabolites |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kunyan Li, Ph.D | Hunan Provincial Tumor Hospital | Principal Investigator |
| Xue Chen, MD | Hunan Provincial Tumor Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hunan Provincial Tumor Hospital | Changsha | Hunan | 410006 | China |
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| Osimertinib Mesylate Tablets under Fasted Condition - Arm1 | Drug | Phase 1 (period 2) fasted from 10 hours prior to dosing with 80 mg Osimertinib Mesylate Tablets (p o, once) and 4 hours after dosing on day 1. |
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| TY-9591 Tablets after a High-fat Meal - Arm1 | Drug | Phase 2 (period 3) allocated high-fat meal prior to dosing with 80 mg TY-9591 tablet (p o, once) and 4 hours after dosing on day 1. |
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| Osimertinib Mesylate Tablets under Fasted Condition - Arm2 | Drug | Phase 1 (period 1) fasted from 10 hours prior to dosing with 80 mg Osimertinib Mesylate Tablets (p o, once) and 4 hours after dosing on day 1. |
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| TY-9591 Tablets under Fasted Condition - Arm2 | Drug | Phase 1 (period 2) fasted from 10 hours prior to dosing with 80 mg TY-9591 tablet (p o, once) and 4 hours after dosing on day 1. |
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| TY-9591 Tablets after a High-fat Meal - Arm2 | Drug | Phase 2 (period 3) allocated high-fat meal prior to dosing with 80 mg TY-9591 tablet (p o, once) and 4 hours after dosing on day 1. |
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Pharmacokinetics of Osimertinib and its metabolites by assessment of time to Cmax. |
| Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| T1/2 of TY-9591 and its metabolites | Pharmacokinetics of TY-9591 and its metabolites by assessment of Terminal half life. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| T1/2 of Osimertinib and its metabolites | Pharmacokinetics of Osimertinib and its metabolites by assessment of Terminal half life. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| λz of TY-9591 and its metabolites | Pharmacokinetics of TY-9591 and its metabolites by assessment of Terminal rate constant. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| λz of Osimertinib and its metabolites | Pharmacokinetics of Osimertinib and its metabolites by assessment of Terminal rate constant. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| AUC(0-168h) of TY-9591 and its metabolites | Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to 168 hours. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| AUC(0-168h) of Osimertinib and its metabolites | Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to 168 hours. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| AUC(0-t) of TY-9591 and its metabolites | Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to appointed time. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| AUC(0-t) of Osimertinib and its metabolites | Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to appointed time. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| AUC(0-∞) of TY-9591 and its metabolites | Pharmacokinetics of TY-9591 and its metabolites by assessment of area under the plasma concentration time curve from zero to infinity. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| AUC(0-∞) of Osimertinib and its metabolites | Pharmacokinetics of Osimertinib and its metabolites by assessment of area under the plasma concentration time curve from zero to infinity. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| CL/F of TY-9591 | Pharmacokinetics of TY-9591 only by assessment of apparent plasma clearance. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| CL/F of Osimertinib | Pharmacokinetics of Osimertinib only by assessment of apparent plasma clearance. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| Vss/F of TY-9591 | Pharmacokinetics of TY-9591 only apparent volume of distribution. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| Vss/F of Osimertinib | Pharmacokinetics of Osimertinib only apparent volume of distribution. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| Calculated for both Cmax and AUC of TY-9591 | Pharmacokinetics of TY-9591 parent to metabolite ratio. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| Calculated for both Cmax and AUC of Osimertinib | Pharmacokinetics of Osimertinib parent to metabolite ratio. | Blood samples are collected at pre-dose (within 1 hour) and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336 hours post-dose. |
| Safety variables | Adverse events, clinical symptoms, vital signs, ECG's, clinical laboratory safety tests, ect. | Assessments performed throughout the study period. |
| ID | Term |
|---|---|
| C000596361 | osimertinib |
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