A Study to Evaluate the Effects of D-1553 on PK of Midazolam, Caffeine, Rosuvastatin, Furosemide, Digoxin, and Itraconazole or Omeprazole on PK of D-1553

Study Overview
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Brief Summary
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This is a phase I study to evaluate drug-drug interactions (DDIs) of D-1553 as a perpetrator combined with midazolam (CYP3A4 substrate), caffeine (CYP1A2 substrate), rosuvastatin (OATP1B1/OATP1B3 substrate), furosemide (OAT1/OATP1B3 substrate), and digoxin (P-gp substrate) and to evaluate DDIs of D-1553 as a victim combined with itraconazole (inhibitor of CYP3A4 and P-gp) and omeprazole (proton-pump inhibitor) in healthy male subjects.

Official Title
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A Phase I Study to Evaluate the Effects of Multiple-dose D-1553 on Pharmacokinetics of Single-dose Midazolam, Caffeine, Rosuvastatin, Furosemide and Digoxin, and to Evaluate the Effects of Multiple-dose Itraconazole and Omeprazole on Pharmacokinetics of Single-dose D-1553 in Healthy Male Subjects

Conditions
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Healthy Male

Intervention / Treatment
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* Drug: D-1553


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who volunteer to participate in this clinical trial, understand the study procedures and sign the Informed Consent Form (ICF) in writing. Male, aged 18-45 years (both inclusive) at the time of signing the ICF. Non-smokers or subjects who smoked no more than 5 cigarettes or 1 pipe per day within 3 months prior to screening. Exclusion Criteria: Subjects with any clinically significant acute diseases as judged by the investigators within one month prior to screening. Subjects who are positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or Treponema pallidum antibody. Subjects with a history of blood or needle phobia. Subjects with a history of hypersensitivity to the investigational drug and/or any preparation ingredients.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multipledose D-1553 on PK of single dose midazolam, caffeine, rosuvastatin, furosemide, digoxin<br>To evaluate the effects of multiple-dose D-1553 tablets on pharmacokinetics (PK) of single-dose midazolam, caffeine, rosuvastatin, furosemide, and digoxin in healthy male subjects. | Drug: D-1553<br>* D-1553 is a novel, targeted KRASG12C inhibitor.<br>* Other names: other;|
| Experimental: Evaluate the effects of multiple-dose itraconazole on PK of single-dose D-1553<br>To evaluate the effects of multiple-dose itraconazole on PK of single-dose D-1553 tablets in healthy male subjects. | Drug: D-1553<br>* D-1553 is a novel, targeted KRASG12C inhibitor.<br>* Other names: other;|
| Experimental: Evaluate the effects of multiple-dose omeprazole on PK of single-dose D-1553<br>To evaluate the effects of multiple-dose omeprazole on PK of single-dose D-1553 tablets in healthy male subjects. | Drug: D-1553<br>* D-1553 is a novel, targeted KRASG12C inhibitor.<br>* Other names: other;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary PK parameters of midazolam, caffeine, rosuvastatin, furosemide, and digoxin: maximum concentration (Cmax). | Primary PK parameters of midazolam, caffeine, rosuvastatin, furosemide, and digoxin before and after co-administration of D-1553 tablets: maximum concentration (Cmax). | Before and after co-administration of D-1553, approximately day1 and day10 | 
| Primary PK parameters of midazolam, caffeine, rosuvastatin, furosemide, and digoxin: area under the concentration-time curve from the time of dosing to time t (AUC0-t). | Primary PK parameters of midazolam, caffeine, rosuvastatin, furosemide, and digoxin before and after co-administration of D-1553 tablets: area under the concentration-time curve from the time of dosing to time t (AUC0-t). | Before and after co-administration of D-1553, approximately day1 and day10 | 
| Primary PK parameters of midazolam, caffeine, rosuvastatin, furosemide, and digoxin: area under the concentration-time curve from time 0 to infinity (AUC0-∞). | Primary PK parameters of midazolam, caffeine, rosuvastatin, furosemide, and digoxin before and after co-administration of D-1553 tablets: area under the concentration-time curve from time 0 to infinity (AUC0-∞). | Before and after co-administration of D-1553, approximately day1 and day10 | 
| Primary PK parameters of D-1553: maximum concentration (Cmax). | Primary PK parameters of D-1553 before and after co-administration of itraconazole: maximum concentration (Cmax). | Before and after co-administration of itraconazole, approximately day1 and day9 | 
| Primary PK parameters of D-1553: area under the concentration-time curve from the time of dosing to time t (AUC0-t). | Primary PK parameters of D-1553 before and after co-administration of itraconazole: area under the concentration-time curve from the time of dosing to time t (AUC0-t). | Before and after co-administration of itraconazole, approximately day1 and day9 | 
| Primary PK parameters of D-1553: area under the concentration-time curve from time 0 to infinity (AUC0-∞). | Primary PK parameters of D-1553 before and after co-administration of itraconazole: area under the concentration-time curve from time 0 to infinity (AUC0-∞). | Before and after co-administration of itraconazole, approximately day1 and day9 | 
| Primary PK parameters of D-1553: maximum concentration (Cmax). | Primary PK parameters of D-1553 before and after co-administration of omeprazole: maximum concentration (Cmax). | Before and after co-administration of omeprazole, approximately day1 and day8 | 
| Primary PK parameters of D-1553: area under the concentration-time curve from the time of dosing to time t (AUC0-t). | Primary PK parameters of D-1553 before and after co-administration of omeprazole: area under the concentration-time curve from the time of dosing to time t (AUC0-t). | Before and after co-administration of omeprazole, approximately day1 and day8 | 
| Primary PK parameters of D-1553: area under the concentration-time curve from time 0 to infinity (AUC0-∞). | Primary PK parameters of D-1553 before and after co-administration of omeprazole: area under the concentration-time curve from time 0 to infinity (AUC0-∞). | Before and after co-administration of omeprazole, approximately day1 and day8 |