A Clinical Study to Evaluate the Effect of Hepatic Impairment on the Single-Dose Pharmacokinetics of MK-1084
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 32
- Locations
- 5
- Primary Endpoint
- Area Under the Concentration Versus Time Curve from 0 to the Time of the Last Quantifiable Sample (AUC0-last) of Calderasib
Study Overview
Brief Summary
The purpose of this study is to learn what happens to calderasib levels in a person's body over time. Researchers will measure what happens to calderasib levels in the body when it is given to participants with hepatic (liver) impairment and healthy participants. Researchers also want to learn about the safety of MK-1084 when it is given to people with hepatic impairment and if people with hepatic impairment can tolerate it.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •The main inclusion criteria include but are not limited to:
- •All participants:
- •Has a body mass index (BMI) between 18.0 and 42.0 kg/m^2
- •Participants with hepatic impairment (HI):
- •Has a diagnosis of chronic, stable hepatic insufficiency at screening with features of cirrhosis
- •Healthy volunteers:
- •Is medically healthy with no clinically significant medical history
Exclusion Criteria
- •include but are not limited to:
- •All participants:
- •Has a history of gastrointestinal disease which may affect food and drug absorption
- •Has a history of cancer (malignancy)
- •Has a positive result for human immunodeficiency virus (HIV)
- •Has had major surgery and/or donated or lost significant volume of blood within 56 days prior to dosing
- •Participants with HI:
- •Has had severe complications of liver disease within the preceding 3 months of screening
- •Has a history of recent (within 3 months prior to screening) variceal bleeds
- •Has evidence of hepatorenal syndrome
- •Is not in sufficient health, with regard to stability of HI, to undergo participation in the study with anticipated survival of < 3 months
- •Has a history of liver or other solid organ transplantation
- •Has an active infection requiring systemic therapy
- •Requires paracentesis more often than 2 times per month
- •Has transjugular intrahepatic portosystemic shunt and/or has undergone portacaval shunting
- •Has received antiviral and/or immune modulating therapy for hepatitis B virus (HBV) or hepatitis C virus (HCV) within 90 days prior to dosing
- •Is using HIV protease inhibitors
- •Is positive for Hepatitis B surface antigen (HBsAg)
- •Is positive for HCV
- •Healthy volunteers:
- •Has positive results for HBsAg or HCV
Arms & Interventions
Calderasib
All participants will receive a single oral dose of calderasib on Day 1.
Intervention: Calderasib (Drug)
Outcomes
Primary Outcomes
Area Under the Concentration Versus Time Curve from 0 to the Time of the Last Quantifiable Sample (AUC0-last) of Calderasib
Time Frame: At designated timepoints up to approximately 7 days post-dose
Blood samples will be collected to determine the AUC0-last of calderasib in plasma.
Area Under the Concentration Versus Time Curve from 0 to Infinity (AUC0-inf) of Calderasib
Time Frame: At designated timepoints up to approximately 7 days post-dose
Blood samples will be collected to determine the AUC0-inf of calderasib in plasma.
Area Under the Concentration Versus Time Curve from 0 to 24 hours post-dose (AUC0-24) of Calderasib
Time Frame: Up to approximately 24 hours post-dose
Blood samples will be collected to determine the AUC0-24 of calderasib in plasma.
Maximum Observed Drug Concentration (Cmax) of Calderasib
Time Frame: At designated timepoints up to approximately 7 days post-dose
Blood samples will be collected to determine the Cmax of calderasib in plasma.
Time to Maximum Observed Drug Concentration (Tmax) of Calderasib
Time Frame: At designated timepoints up to approximately 7 days post-dose
Blood samples will be collected to determine the Tmax of calderasib in plasma.
Apparent Terminal Half-life (t1/2) of Calderasib
Time Frame: At designated timepoints up to approximately 7 days post-dose
Blood samples will be collected to determine the t1/2 of calderasib in plasma.
Apparent Clearance (CL/F) of Calderasib
Time Frame: At designated timepoints up to approximately 7 days post-dose
Blood samples will be collected to determine the CL/F of calderasib in plasma.
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Calderasib
Time Frame: At designated timepoints up to approximately 7 days post-dose
Blood samples will be collected to determine the Vz/F of calderasib in plasma.
Secondary Outcomes
- Number of Participants Who Experience an Adverse Event (AE)(Up to approximately 14 days)
- Number of Participants Who Discontinue Study Due to an AE(Up to approximately 14 days)