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

Phase 1
Completed
Conditions
Non-small Cell Lung Cancer
Interventions
Registration Number
NCT06575933
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

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 MK-1084. Researchers are testing if digoxin and midazolam levels in the body are different when digoxin and midazolam are given with or without MK-1084.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
28
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Period 2: MK-1084, Midazolam, and DigoxinMidazolamA washout period of at least 10 days will occur following midazolam and digoxin dosing in Period 1 and the first MK-1084 dosing in Period 2. Participants will receive MK-1084 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.
Period 2: MK-1084, Midazolam, and DigoxinMK-1084A washout period of at least 10 days will occur following midazolam and digoxin dosing in Period 1 and the first MK-1084 dosing in Period 2. Participants will receive MK-1084 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.
Period 1: Midazolam and DigoxinMidazolamParticipants will receive a single oral dose of midazolam and a single oral dose of digoxin on Day 1.
Period 1: Midazolam and DigoxinDigoxinParticipants will receive a single oral dose of midazolam and a single oral dose of digoxin on Day 1.
Period 2: MK-1084, Midazolam, and DigoxinDigoxinA washout period of at least 10 days will occur following midazolam and digoxin dosing in Period 1 and the first MK-1084 dosing in Period 2. Participants will receive MK-1084 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.
Primary Outcome Measures
NameTimeMethod
CL/F of DigoxinPredose and at designated timepoints up to 120 hours postdose

Blood samples will be collected to determine the CL/F of digoxin.

Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of MidazolamPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the AUC0-last of midazolam.

Maximum Plasma Concentration (Cmax) of MidazolamPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the Cmax of midazolam.

Area Under the Concentration-Time Curve from Time 0 to 24 hours (AUC0-24hr) of MidazolamPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the AUC0-24hr of midazolam.

Cmax of DigoxinPredose and at designated timepoints up to 120 hours postdose

Blood samples will be collected to determine the Cmax of digoxin.

Vz/F of DigoxinPredose and at designated timepoints up to 120 hours postdose

Blood samples will be collected to determine the Vz/F of digoxin.

Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of MidazolamPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the AUC0-inf of midazolam.

t1/2 of DigoxinPredose and at designated timepoints up to 120 hours postdose

Blood samples will be collected to determine the t1/2 of digoxin.

Apparent Clearance (CL/F) of MidazolamPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the CL/F of midazolam.

Tmax of DigoxinPredose and at designated timepoints up to 120 hours postdose

Blood samples will be collected to determine the Tmax of digoxin.

Time to Maximum Plasma Concentration (Tmax) of MidazolamPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the Tmax of midazolam.

Apparent Volume of Distribution During Terminal Phase (Vz/F) of MidazolamPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the Vz/F of midazolam.

AUC0-Last of DigoxinPredose and at designated timepoints up to 120 hours postdose

Blood samples will be collected to determine the AUC0-last of digoxin.

AUC0-24hr of DigoxinPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the AUC0-24hr of digoxin.

Apparent Terminal Half-life (t1/2) of MidazolamPredose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the t1/2 of midazolam.

AUC0-Inf of DigoxinPredose and at designated timepoints up to 120 hours postdose

Blood samples will be collected to determine the AUC0-inf of digoxin.

Secondary Outcome Measures
NameTimeMethod
Cmax Accumulation Ratio of MK-1084Predose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the Cmax accumulation ratio of MK-1084. The accumulation ratio is the ratio of Predose Cmax to the 24 hour Cmax

AUC0-24 Accumulation Ratio of MK-1084Predose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the AUC0-24 accumulation ratio of MK-1084. The accumulation ratio is the ratio of Predose AUC0-24 to the 24 hour AUC0-24.

Number of Participants Who Experience an Adverse Event (AE)Up to approximately 1 month

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.

AUC0-24hr of MK-1084Predose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the AUC0-24hr of MK-1084.

Fraction of Unchanged Digoxin in Urine (Fe)Predose and at designated timepoints up to 120 hours postdose

Urine samples will be collected to determine the Fe of digoxin.

Number of Participants Who Discontinue Study Due to an AEUp to approximately 1 month

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.

AUC0-Last of MK-1084Predose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the AUC0-last of MK-1084.

Cmax of MK-1084Predose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the Cmax of MK-1084.

Amount of Drug Excreted in Urine from Time 1 to Time 2 (Aet1-t2) of DigoxinPredose and at designated timepoints up to 120 hours postdose

Urine samples will be collected to determine the Aet1-t2 of digoxin.

C24 of MK-1084Predose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the Cmax of MK-1084.

Tmax of MK-1084Predose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the Tmax of MK-1084.

t1/2 of MK-1084Predose and at designated timepoints up to 24 hours postdose

Blood samples will be collected to determine the t1/2 of MK-1084.

Total Amount of Drug Excreted in Urine (Ae) of DigoxinPredose and at designated timepoints up to 120 hours postdose

Urine samples will be collected to determine the Ae of digoxin.

Trial Locations

Locations (1)

Celerion ( Site 0001)

🇺🇸

Tempe, Arizona, United States

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