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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Male
• Intervention / Treatment: Drug: D-1553

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200031
      • Shanghai Xuhui District Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: InventisBio Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2023
• Primary Completion (Actual): February 2, 2024
• Study Completion (Actual): February 2, 2024

Study Registration Dates

• First Submitted: October 17, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: D1553-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No