A Clinical Trial of MK-4646 With Bictegravir/Emtricitabine/Tenofovir Alafenamide and Dolutegravir in Healthy Adult Participants (MK-4646)

A Drug-Drug Interaction Study of MK-4646 With Bictegravir/Emtricitabine/Tenofovir Alafenamide and Dolutegravir

Researchers are looking for new treatments for people living with HIV-1(Human Immunodeficiency Virus Type 1). HIV-1 is the most common type of HIV, which is a virus that attacks cells of the immune system.

HIV-1 treatments, called ART (antiretroviral therapy), involve taking medicines to lower the amount of HIV-1 virus in the body. Standard ART may include Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) and Dolutegravir (DTG).

MK-4646 is a trial medicine designed to treat HIV-1. Before giving a trial medicine to people with a health condition, researchers first do trials in healthy people.

The goals of this study are to learn:

• If taking MK 4646 together with BIC/FTC/TAF or DTG changes the amount of these ARTs in the blood over time.
• About the safety of MK-4646 and if people tolerate it. Tolerate means participants will receive treatment in the trial unless they need to stop it due to health problems.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Drug: Dolutegravir; Drug: MK4646

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Recruiting
      • Pinnacle Research Group ( Site 0001)
      • Contact: Study Coordinator; Phone Number: 256-236-0055

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Is in good health before randomization
• Has a body mass index (BMI) between 18 and 32 kg/m^2, inclusive

Exclusion Criteria:

• Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
• Has a history of cancer (malignancy)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF); Participants will receive a single oral dose of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).	Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Single oral tablet
Experimental: Treatment B: dolutegravir (DTG); Participants will receive a single oral dose of dolutegravir (DTG).	Drug: Dolutegravir; Oral tablet
Experimental: Treatment C: MK-4646 + bictegravir/ emtricitabine/tenofovir alafenamide (BIC/FTC/TAF); Participants will receive a single oral dose of MK-4646 coadministered with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).	Drug: Bictegravir/emtricitabine/tenofovir alafenamide; Single oral tablet; Drug: MK4646; Oral capsule
Experimental: Treatment D: MK-4646 + dolutegravir (DTG); Participants will receive a single oral dose of MK-4646 coadministered with dolutegravir (DTG).	Drug: Dolutegravir; Oral tablet; Drug: MK4646; Oral capsule

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-∞) of Bictegravir	Blood samples will be collected to determine the AUC0-∞ of bictegravir.	At designated timepoints (up to approximately 72 hours post dose)
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of Emtricitabine	Blood samples will be collected to determine the AUC0-∞ of emtricitabine.	At designated timepoints (up to approximately 72 hours post dose)
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of Tenofovir Alafenamide	Blood samples will be collected to determine the AUC0-∞ of tenofovir alafenamide.	At designated timepoints (up to approximately 72 hours post dose)
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of Tenofovir	Blood samples will be collected to determine the AUC0-∞ of tenofovir.	At designated timepoints (up to approximately 72 hours post dose)
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) of Dolutegravir	Blood samples will be collected to determine the AUC0-∞ of dolutegravir.	At designated timepoints (up to approximately 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 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 44 days
Number of Participants Who Discontinue Study Treatment 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 treatment due to an AE will be reported.	Up to approximately 31 Days
Maximum Plasma Concentration (Cmax) of Bictegravir	Blood samples will be collected to determine the Cmax of bictegravir.	At designated timepoints (up to approximately 72 hours post dose)
Time to Maximum Plasma Concentration (Tmax) of Bictegravir	Blood samples will be collected to determine the Tmax of bictegravir.	At designated timepoints (up to approximately 72 hours post dose)
Apparent Terminal Half-life (t½) of Bictegravir	Blood samples will be collected to determine the t½ of bictegravir.	At designated timepoints (up to approximately 72 hours post dose)
Maximum Plasma Concentration (Cmax) of Emtricitabine	Blood samples will be collected to determine the Cmax of emtricitabine.	At designated timepoints (up to approximately 72 hours post dose)
Time to Maximum Plasma Concentration (Tmax) of Emtricitabine	Blood samples will be collected to determine the Tmax of emtricitabine.	At designated time points (up to approximately 72 hours post dose)
Apparent Terminal Half-life (t½) of Emtricitabine	Blood samples will be collected to determine the t½ of emtricitabine.	At designated timepoints (up to approximately 72 hours post dose)
Maximum Plasma Concentration (Cmax) of Tenofovir	Blood samples will be collected to determine the Cmax of tenofovir.	At designated timepoints (up to approximately 72 hours post dose)
Time to Maximum Plasma Concentration (Tmax) of Tenofovir	Blood samples will be collected to determine the Tmax of tenofovir.	At designated timepoints (up to approximately 72 hours post dose)
Apparent Terminal Half-life (t½) of Tenofovir	Blood samples will be collected to determine the t½ of tenofovir.	At designated timepoints (up to approximately 72 hours post dose)
Maximum Plasma Concentration (Cmax) of Dolutegravir	Blood samples will be collected to determine the Cmax of dolutegravir.	At designated timepoints (up to approximately 72 hours post dose)
Time to Maximum Plasma Concentration (Tmax) of Dolutegravir	Blood samples will be collected to determine the Tmax of dolutegravir.	At designated timepoints (up to approximately 72 hours post dose)
Apparent Terminal Half-life (t½) of Dolutegravir	Blood samples will be collected to determine the t½ of dolutegravir.	At designated timepoints (up to approximately 72 hours post dose)
Plasma Concentration at 24 Hours (C24) of Bictegravir	Blood samples will be collected to determine the C24 of bictegravir.	24 hours post dose
Plasma Concentration at 24 Hours (C24) of Emtricitabine	Blood samples will be collected to determine the C24 of emtricitabine.	24 hours post dose
Maximum Plasma Concentration (Cmax) of Tenofovir Alafenamide	Blood samples will be collected to determine the Cmax of tenofovir alafenamide.	At designated timepoints (up to approximately 72 hours post dose)
Plasma Concentration at 24 Hours (C24) of Tenofovir Alafenamide	Blood samples will be collected to determine the C24 of tenofovir alafenamide.	At designated time points (up to approximately 24 hours post dose)
Time to Maximum Plasma Concentration (Tmax) of Tenofovir Alafenamide	Blood samples will be collected to determine the Tmax of tenofovir alafenamide.	At designated time points (up to approximately 72 hours post dose)
Apparent Terminal Half-life (t½) of Tenofovir Alafenamide	Blood samples will be collected to determine the t½ of tenofovir alafenamide.	At designated timepoints (up to approximately 72 hours post dose)
Plasma Concentration at (C24) of Tenofovir	Blood samples will be collected to determine the C24 of tenofovir.	24 hours post dose
Plasma Concentration at (C24) of Dolutegravir	Blood samples will be collected to determine the C24 of dolutegravir.	24 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 11, 2026
• Primary Completion (Estimated): July 21, 2026
• Study Completion (Estimated): July 21, 2026

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: dolutegravir; bictegravir, emtricitabine, tenofovir alafenamide, drug combination
• Other Study ID Numbers: 4646-006; MK-4646-006 (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