A Study of Calderasib (MK-1084) With Midazolam and Digoxin in Healthy Participants (MK-1084-009)

A Study to Evaluate the Effect of Single and Multiple Doses of MK-1084 on the Single-Dose Pharmacokinetics of Midazolam and Digoxin in Healthy Participants

The goal of the study is to see what happens to levels of midazolam and digoxin in a person's body over time (a pharmacokinetic or PK study). Researchers will compare what happens to midazolam and digoxin in the body when it is given with and without another medicine called calderasib. Researchers are testing if digoxin and midazolam levels in the body are different when digoxin and midazolam are given with or without calderasib.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Midazolam; Drug: Digoxin; Drug: Calderasib

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

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion ( Site 0001)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

• Is medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vitals signs, and electrocardiograms (ECGs)
• Has a body mass index (BMI) ≥18 and ≤32 kg/m^2, inclusive

Exclusion Criteria:

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

• Has a medical history that may confound the results of the study or poses an additional risk to the participant in the study
• Has a history or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: Midazolam and Digoxin; Participants will receive a single oral dose of midazolam and a single oral dose of digoxin on Day 1.	Drug: Midazolam; Oral administration; Drug: Digoxin; Oral administration
Experimental: Period 2: Calderasib, Midazolam, and Digoxin; A washout period of at least 10 days will occur following midazolam and digoxin dosing in Period 1 and the first calderasib dosing in Period 2. Participants will receive calderasib once daily on Days 1 through Day 15 with a single oral dose of midazolam on Days 1, 6, and 14 and a single oral dose of digoxin on Days 1 and 11.	Drug: Midazolam; Oral administration; Drug: Digoxin; Oral administration; Drug: Calderasib; Oral administration; 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 (AUC0-Inf) of Midazolam	Blood samples will be collected to determine the AUC0-inf of midazolam.	Predose and at designated timepoints up to 24 hours postdose
Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of Midazolam	Blood samples will be collected to determine the AUC0-last of midazolam.	Predose and at designated timepoints up to 24 hours postdose
Area Under the Concentration-Time Curve from Time 0 to 24 hours (AUC0-24hr) of Midazolam	Blood samples will be collected to determine the AUC0-24hr of midazolam.	Predose and at designated timepoints up to 24 hours postdose
Maximum Plasma Concentration (Cmax) of Midazolam	Blood samples will be collected to determine the Cmax of midazolam.	Predose and at designated timepoints up to 24 hours postdose
Time to Maximum Plasma Concentration (Tmax) of Midazolam	Blood samples will be collected to determine the Tmax of midazolam.	Predose and at designated timepoints up to 24 hours postdose
Apparent Terminal Half-life (t1/2) of Midazolam	Blood samples will be collected to determine the t1/2 of midazolam.	Predose and at designated timepoints up to 24 hours postdose
Apparent Clearance (CL/F) of Midazolam	Blood samples will be collected to determine the CL/F of midazolam.	Predose and at designated timepoints up to 24 hours postdose
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Midazolam	Blood samples will be collected to determine the Vz/F of midazolam.	Predose and at designated timepoints up to 24 hours postdose
AUC0-Inf of Digoxin	Blood samples will be collected to determine the AUC0-inf of digoxin.	Predose and at designated timepoints up to 120 hours postdose
AUC0-Last of Digoxin	Blood samples will be collected to determine the AUC0-last of digoxin.	Predose and at designated timepoints up to 120 hours postdose
AUC0-24hr of Digoxin	Blood samples will be collected to determine the AUC0-24hr of digoxin.	Predose and at designated timepoints up to 24 hours postdose
Cmax of Digoxin	Blood samples will be collected to determine the Cmax of digoxin.	Predose and at designated timepoints up to 120 hours postdose
Tmax of Digoxin	Blood samples will be collected to determine the Tmax of digoxin.	Predose and at designated timepoints up to 120 hours postdose
t1/2 of Digoxin	Blood samples will be collected to determine the t1/2 of digoxin.	Predose and at designated timepoints up to 120 hours postdose
CL/F of Digoxin	Blood samples will be collected to determine the CL/F of digoxin.	Predose and at designated timepoints up to 120 hours postdose
Vz/F of Digoxin	Blood samples will be collected to determine the Vz/F of digoxin.	Predose and at designated timepoints up to 120 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of Drug Excreted in Urine from Time 1 to Time 2 (Aet1-t2) of Digoxin	Urine samples will be collected to determine the Aet1-t2 of digoxin.	Predose and at designated timepoints up to 120 hours postdose
Total Amount of Drug Excreted in Urine (Ae) of Digoxin	Urine samples will be collected to determine the Ae of digoxin.	Predose and at designated timepoints up to 120 hours postdose
Fraction of Unchanged Digoxin in Urine (Fe)	Urine samples will be collected to determine the Fe of digoxin.	Predose and at designated timepoints up to 120 hours postdose
Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.	Up to approximately 1 month
Number of Participants Who Discontinue Study Due to an AE	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study due to an AE will be reported.	Up to approximately 1 month
AUC0-24hr of Calderasib	Blood samples will be collected to determine the AUC0-24hr of calderasib.	Predose and at designated timepoints up to 24 hours postdose
AUC0-Last of Calderasib	Blood samples will be collected to determine the AUC0-last of calderasib.	Predose and at designated timepoints up to 24 hours postdose
Cmax of Calderasib	Blood samples will be collected to determine the Cmax of calderasib.	Predose and at designated timepoints up to 24 hours postdose
C24 of Calderasib	Blood samples will be collected to determine the Cmax of calderasib.	Predose and at designated timepoints up to 24 hours postdose
Tmax of Calderasib	Blood samples will be collected to determine the Tmax of calderasib.	Predose and at designated timepoints up to 24 hours postdose
t1/2 of Calderasib	Blood samples will be collected to determine the t1/2 of calderasib.	Predose and at designated timepoints up to 24 hours postdose
Cmax Accumulation Ratio of Calderasib	Blood samples will be collected to determine the Cmax accumulation ratio of calderasib. The accumulation ratio is the ratio of Predose Cmax to the 24 hour Cmax	Predose and at designated timepoints up to 24 hours postdose
AUC0-24 Accumulation Ratio of Calderasib	Blood samples will be collected to determine the AUC0-24 accumulation ratio of calderasib. The accumulation ratio is the ratio of Predose AUC0-24 to the 24 hour AUC0-24.	Predose and at designated timepoints up to 24 hours postdose

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): September 3, 2024
• Primary Completion (Actual): October 28, 2024
• Study Completion (Actual): October 28, 2024

Study Registration Dates

• First Submitted: August 26, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 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: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbohydrates; Polycyclic Compounds; Glycosides; Steroids; Fused-Ring Compounds; Benzazepines; Benzodiazepines; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Midazolam; Digoxin
• Other Study ID Numbers: 1084-009; CA43815 (Other Identifier: Celerion Protocol Number); MK-1084-009 (Other Identifier: MSD)

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