A Study of the Effect of Itraconazole and Phenytoin on Calderasib (MK-1084) in Healthy Adults (MK-1084-008)

A Two-Part Study to Evaluate the Effects of Multiple Doses of Itraconazole and Multiple Doses of Phenytoin on the Single-Dose Pharmacokinetics of MK-1084 in Healthy Adult Participants

The goal of this study is to learn what happens to calderasib in a healthy person's body over time, called a pharmacokinetic (PK) study. Researchers want to compare the amount of calderasib when it is taken as a single dose; with multiple doses of itraconazole, or with multiple doses of phenytoin.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Itraconazole; Drug: Phenytoin; Drug: Calderasib

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion (Site 0001)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

- Has body mass index (BMI) ≥18 kg/m^2 and ≤32 kg/m^2

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

• History of cancer (malignancy)
• Positive results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)

Part 1 Only:

- History or presence of ventricular dysfunction or risk factors for Torsades de Pointes (e.g., heart failure, cardiomyopathy, family history of Long QT Syndrome)

Pat 2 Only:

- History of seizure (excluding simple febrile seizure), epilepsy, severe head injury, multiple sclerosis, or other known neurological conditions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Calderasib + Itraconazole; Part 1: In Period 1 participants receive a single dose of calderasib on Day 1 under fasting conditions. In Period 2 participants receive itraconazole once daily (QD) for 7 consecutive days (Day 1 - Day 7), plus a single dose of calderasib administered approximately 2 hours after itraconazole dosing on Day 5. There will be a washout of at least 7 days between dosing in Period 1 and the first dose in Period 2.	Drug: Itraconazole; Oral solution; Drug: Calderasib; Oral Tablet; Other Names: MK-1084
Experimental: Part 2: Calderasib + Phenytoin; Part 2: In Period 1 participants receive a single dose of calderasib on Day 1 under fasting conditions. In Period 2 participants receive phenytoin three times daily (TID) for 14 consecutive days (Day 1 - Day 14), plus a single dose of calderasib co-administered on the morning of Day 13. There will be a washout of at least 7 days between dosing in Period 1 and the first dose in Period 2.	Drug: Phenytoin; Oral capsule (extended); Drug: Calderasib; Oral Tablet; Other Names: MK-1084

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve from Time 0 to Infinity After Single Dosing (AUC0-Inf) of Calderasib	Blood samples will be collected to determine the AUC0-Inf of calderasib.	Pre-dose and at designated time points up to 72 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.	Up to approximately 41 days
Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported.	Up to approximately 25 days
Area Under the Concentration-Time Curve from Time 0 to Last Quantifiable Sample (AUC0-last) of Calderasib	Blood samples will be collected to determine the AUC0-last of calderasib.	Pre-dose and at designated time points up to 72 hours post dose
Area Under the Concentration-Time Curve from Time 0 to 24 hours (AUC0-24) of Calderasib	Blood samples will be collected to determine the AUC0-24 of calderasib.	Pre-dose and at designated time points up to 24 hours post dose
Maximum Plasma Concentration (Cmax) of Calderasib	Blood samples will be collected to determine the Cmax of calderasib.	Pre-dose and at designated time points up to 72 hours post dose
Plasma Concentration at 24 Hours (C24) of Calderasib	Blood samples will be collected to determine the C24 of calderasib.	Pre-dose and at designated time points up to 24 hours post dose
Time to Maximum Plasma Concentration (Tmax) of Calderasib	Blood samples will be collected to determine the Tmax of calderasib.	Pre-dose and at designated time points up to 72 hours post dose
Apparent Terminal Half-life (t1/2) of Calderasib	Blood samples will be collected to determine the t1/2 of calderasib.	Pre-dose and at designated time points up to 72 hours post dose
Apparent Clearance (CL/F) of Calderasib	Blood samples will be collected to determine the CL/F of calderasib.	Pre-dose and at designated time points up to 72 hours post dose
Apparent volume of distribution during terminal phase (Vz/F) of Calderasib	Blood samples will be collected to determine the Vz/F of calderasib.	Pre-dose and at designated time points up to 72 hours post dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Actual): July 30, 2024
• Study Completion (Actual): July 30, 2024

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 2, 2024
• First Posted (Actual): December 6, 2024

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Triazoles; Piperazines; Hydantoins; Imidazolidines; Itraconazole; Phenytoin
• Other Study ID Numbers: 1084-008; MK-1084-008 (Other Identifier: MSD); CA43207 (Other Identifier: Celerion)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

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