A Clinical Trial to Evaluate MK-4208/TERN-701 in Healthy Adult Participants (MK-4208-001/TERN701-1014)

NCT07838987 | Completed Phase 1 FDA Drug

• 2 other identifiers: TERN701-1014MK-4208-001
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the study is to learn what happens to different doses and forms of TERN-701 in a healthy person's body over time. Researchers will compare what happens to different doses and forms of TERN-701 in a person's body over time when given with or without food, or with or without other medications. The goal of the study is to learn:

• What happens to different doses of TERN-701 in a person's body over time when it is given with or without food, or with or without other medications.
• About the safety of TERN-701 and if people tolerate it

Conditions

Healthy

Outcome Measures

Primary Outcomes (14)

• Number of Participants Who Experience a Treatment Emergent 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 a treatment emergent AE will be reported.

  Up to approximately 102 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 102 days

• Number of Participants with Clinically Significant Abnormalities in Systolic Blood Pressure

  Blood pressure will be measured after the participant has been at rest in a supine position for at least 10 minutes. Blood pressure and pulse measurements will be assessed with a completely automated device; manual techniques will be used only if an automated device is not available. Blood pressure measurements will be carried out before blood sample collections or at least 30 minutes after any blood draws.

  up to approximately 102 days

• Number of Participants with Clinically Significant Abnormalities in Diastolic Blood Pressure

  Blood pressure will be measured after the participant has been at rest in a supine position for at least 10 minutes. Blood pressure and pulse measurements will be assessed with a completely automated device; manual techniques will be used only if an automated device is not available. Blood pressure measurements will be carried out before blood sample collections or at least 30 minutes after any blood draws.

  up to approximately 102 days

• Number of Participants with Abnormal Clinical Hematology Test Results Reported as Adverse Events

  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 with abnormal hematology-related AEs will be reported.

  up to approximately 102 days

• Number of Participants with Abnormal Clinical Chemistry Test Results Reported as Adverse Events

  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 with abnormal chemistry-related AEs will be reported.

  up to approximately 102 days

• Number of Participants with Abnormal Urinalysis Results Reported as Adverse Events

  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 with abnormal urinalysis-related AEs will be reported.

  up to approximately 102 days

• Number of Participants with Clinically Significant Abnormalities in 12-Lead (ECG) Findings

  During the 12-lead ECG collection participants will be instructed to lie supine for at least 10 minutes prior to ECG collection. During the collection, participants should be in a quiet setting, without distractions, and should refrain from talking or moving their arms or legs. All ECG acquisitions will be carried out before any blood sample collections or at least 30 minutes after any blood draws.

  up to approximately 102 days

• Area Under the Concentration versus Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) of TERN-701 in Plasma

  Blood samples will be collected to determine the AUC0-Last of TERN-701.

  Pre-dose and at designated time points up to 96 hours post dose

• Area Under the Concentration versus Time Curve Extrapolated to Infinite Time (AUC0-Inf) of TERN-701 in Plasma

  Blood samples will be collected to determine the AUC0-inf of TERN-701.

  Pre-dose and at designated time points up to 96 hours post dose

• Area Under the Concentration versus Time Curve Over the Dosing Interval (AUCtau) of TERN-701 in Plasma

  Blood samples will be collected to determine the AUCtau of TERN-701.

  Pre-dose and at designated time points up to 24 hours post dose

• Maximum Observed Concentration of Drug (Cmax) of TERN-701 in Plasma

  Blood samples will be collected to determine the Cmax of TERN-701.

  Pre-dose and at designated time points up to 96 hours post dose

• Apparent Terminal Elimination Half-Life (t1/2) of TERN-701 in Plasma

  Blood samples will be collected to determine the t1/2 of TERN-701.

  Pre-dose and at designated time points up to 96 hours post dose

• Time of Maximum Observed Concentration of Drug (Tmax) of TERN-701 in Plasma

  Blood samples will be collected to determine the Tmax of TERN-701.

  Pre-dose and at designated time points up to 96 hours post dose

Secondary Outcomes (40)

• AUC0-last of TERN-701 in Plasma Under Fed Versus Fasted Conditions

  Pre-dose and at designated time points up to 96 hours post dose

• AUC0-Inf of TERN-701 in Plasma Under Fed Versus Fasted Conditions

  Pre-dose and at designated time points up to 96 hours post dose

• Cmax of TERN-701 in Plasma Under Fed Versus Fasted Conditions

  Pre-dose and at designated time points up to 96 hours post dose

• Tmax of TERN-701 in Plasma Under Fed Versus Fasted Conditions

  Pre-dose and at designated time points up to 96 hours post dose

• AUC0-last of TERN-701 Formulations in Plasma

  Pre-dose and at designated time points up to 96 hours post dose

Study Arms (19)

Cohort 1: Single Ascending Dose (SAD) Escalation of TERN-701 Dose Level 1

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 1 under fasted conditions on Day 1.

Drug: TERN-701

Cohort 2: SAD Escalation of TERN-701 Dose Level 2

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 2 under fasted conditions on Day 1.

Drug: TERN-701

Cohort 3: SAD Escalation of TERN-701 Dose Level 3 and Food Effect

EXPERIMENTAL

On Period 1 Day 1, participants receive a single oral dose of TERN-701 Dose Level 3 under fasted conditions. On Period 2 Day 1, participants receive TERN-701 Dose Level 3 after a high-fat meal.

Drug: TERN-701

Cohort 4: SAD Escalation of TERN-701 Dose Level 4

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 4 under fasted conditions on Day 1.

Drug: TERN-701

Cohort 5: SAD Escalation of TERN-701 Dose Level 5

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 5 under fasted conditions on Day 1.

Drug: TERN-701

Cohort 6: SAD Escalation of TERN-701 Dose Level 7

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 7 under fasted conditions on Day 1.

Drug: TERN-701

Cohort 7: TERN-701 Formulations with Rabeprazole 20 mg

EXPERIMENTAL

Participants in Cohort 7 are randomized to receive TERN-701 Formulation 1 or Formulation 2 at Dose Level 5 on Day 1. On Day 7, participants receive TERN-701 Formulation 2 or Formulation 1 at Dose Level 5. Participants also receive Rabeprazole 20 mg once daily on Days 10-13. On Day 14, participants will co-administer a single oral dose of Rabeprazole 20 mg with TERN-701 Formulation 1 Dose Level 5 at the same time. All participants receive treatment under fasted conditions.

Drug: TERN-701; Drug: Rabeprazole

Cohort 8: TERN-701 + Probe Substrate Cocktail-1

EXPERIMENTAL

Per protocol, the probe substrate cocktail-1 consists of midazolam 2 mg, digoxin 0.25 mg, pravastatin 40 mg, montelukast 10 mg, and omeprazole 40 mg. On Day 1, participants receive a single oral dose of the probe substrate cocktail-1 under fasted conditions. On Day 5, participants receive a single oral dose of TERN-701 Dose Level 4 co-administered with a single oral dose of the probe substrate cocktail-1 taken at the same time under fasted conditions. On Day 9, participants receive a single oral dose of TERN-701 Dose Level 7 co-administered with a single oral dose of the probe substrate cocktail-1 taken at the same time under fasted conditions.

Drug: TERN-701; Drug: Midazolam; Drug: Digoxin; Drug: Pravastatin; Drug: Montelukast; Drug: Omeprazole

Cohort 9: TERN-701 Dose Level 5 + Rabeprazole 20 mg

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 5 on Day 1 under fasted conditions. On Days 4-7 participants will receive Rabeprazole 20 mg once daily under fasted conditions. On Day 8, under fasted conditions, participants co-administer a single oral dose of TERN-701 Dose Level 5 with a single oral dose of Rabeprazole 20 mg taken at the same time under fasted conditions.

Drug: TERN-701; Drug: Rabeprazole

Cohort 10: SAD Escalation of TERN-701 Dose Level 8

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 8 under fasted conditions on Day 1.

Drug: TERN-701

Cohort 11: SAD Escalation of TERN-701 Dose Level 9

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 9 under fasted conditions on Day 1.

Drug: TERN-701

Cohort 12: TERN-701 Dose Level 3 + Itraconazole 200 mg

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 at Dose Level 3 under nonfasted conditions on Day 1. On Day 8, participants will receive Itraconazole 200 mg twice daily after a standardized breakfast and evening snack. On Days 9-11, participants will take a single oral dose of Itraconazole 200 mg after a standardized meal. On Day 12, participants will take a single dose of Itraconazole 200mg after a standardized meal followed by TERN-701 Dose Level 3 taken an hour later. Participants will continue taking a single oral dose of Itraconazole 200 mg once daily after a standardized meal on Days 13-15.

Drug: TERN-701; Drug: Itraconazole

Cohort 13: Multiple Ascending Dose (MAD) Escalation of TERN-701 Dose Level 4

EXPERIMENTAL

Participants receive an oral dose of TERN-701 Dose Level 4 once daily from Day 1 to Day 13 under fasted conditions.

Drug: TERN-701

Cohort 14: TERN-701 Dose Level 5 + Probe Substrate Cocktail-2

EXPERIMENTAL

Per protocol, the probe substrate cocktail-2 consists of midazolam 2 mg, warfarin 5 mg, and rosuvastatin 10 mg. Participants receive a single oral dose of the Probe Substrate Cocktail-2 on Day 1 under fasted conditions. On Days 9-15, participants receive a single oral dose of TERN-701 Dose Level 5 once daily under fasted conditions. On Day 16, participants receive a single oral dose of the Probe Substrate Cocktail-2 co-administered with TERN-701 Dose Level 5 taken at the same time under fasted conditions. On Days 17-21 participants receive TERN-701 Dose Level 5 as a single oral dose once daily under fasted conditions.

Drug: TERN-701; Drug: Midazolam; Drug: Warfarin; Drug: Rosuvastatin

Cohort 15: TERN-701 Dose Level 8 + Probe Substrate Cocktail-2

EXPERIMENTAL

Per protocol, the probe substrate cocktail-2 consists of midazolam 2 mg, warfarin 5 mg, and rosuvastatin 10 mg. Participants receive a single oral dose of the Probe Substrate Cocktail-2 on Day 1 under fasted conditions. On Days 9-15, participants receive a single oral dose of TERN-701 Dose Level 8 once daily under fasted conditions. On Day 16, participants receive a single oral dose of the Probe Substrate Cocktail-2 co-administered with TERN-701 Dose Level 8 taken at the same time under fasted conditions. On Days 17-21 participants receive TERN-701 Dose Level 8 as a single oral dose once daily under fasted conditions.

Drug: TERN-701; Drug: Midazolam; Drug: Warfarin; Drug: Rosuvastatin

Cohort 16: Food Effect on TERN-701 Dose Level 8 Formulations with Rabeprazole 20 mg

EXPERIMENTAL

On Period 1 Day 1, participants receive a single oral dose of TERN-701 Formulation 3 Dose Level 8. On Period 1 Day 7, participants receive a single oral dose of TERN-701 Formulation 4 Dose Level 8. On Period 1 Day 13, participants receive a single oral dose of TERN-701 Formulation 5 Dose Level 8. On Period 1 Day 19, participants receive a single oral dose of TERN-701 Formulation 6 Dose Level 8. All Period 1 treatments are administered under fasted conditions. Per protocol, following Period 1, one formulation is selected for Period 2. On Period 2 Day 1, participants receive a single oral dose of the selected TERN-701 formulation Dose Level 8 after a high-fat meal. On Period 2 Days 7-10, participants receive rabeprazole 20 mg once daily under fasted conditions. On Period 2 Day 11, participants receive the selected formulation of TERN-701 Dose Level 8 as a single oral dose, co-administered with the single oral dose of Rabeprazole 20 mg taken at the same time under fasted conditions.

Drug: TERN-701; Drug: Rabeprazole

Cohort 17: Food Effect on TERN-701 Dose Level 8 Selected Formulation with Rabeprazole 20 mg

EXPERIMENTAL

Per protocol, a formulation from Cohort 16 Period 1, different from the formulation selected for Cohort 16 Period 2, may be selected to evaluate the effects of food and rabeprazole 20 mg. On Day 1, participants receive a single oral dose of the selected formulation of TERN-701 Dose Level 8 under fasted conditions. On Day 7, participants receive a single oral dose of the selected formulation of TERN-701 Dose Level 8 after a high-fat meal. On Days 13-16, participants receive a single oral dose of rabeprazole 20 mg once daily. On Day 17, participants receive a single oral dose of the selected formulation of TERN-701 Dose Level 8 co-administered with a single oral dose of rabeprazole 20 mg taken at the same time under fasted conditions.

Drug: TERN-701; Drug: Rabeprazole

Cohort 18: TERN-701 Dose Level 8 + Bosentan 125 mg

EXPERIMENTAL

On Day 1, participants receive a single oral dose of TERN-701 Dose Level 8 under fasted conditions. Beginning on Day 8, participants receive an oral dose of Bosentan 125 mg twice daily. On Day 15, participants receive TERN-701 Dose Level 8 as a single oral dose co-administered with the morning dose of Bosentan 125 mg taken at the same time under fasted conditions; participants then receive the second daily dose of Bosentan 125 mg in the evening. Participants continue taking Bosentan 125 mg twice daily on Days 16-18.

Drug: TERN-701; Drug: Bosentan

Cohort 19: TERN-701 Dose Level 6 + Quinidine 300 mg

EXPERIMENTAL

Participants receive a single oral dose of TERN-701 Dose Level 6 on Day 1 under fasted conditions. Beginning on Day 6, participants receive an oral dose of Quinidine 300 mg three times daily. On Day 8, participants receive TERN-701 Dose Level 6 as a single oral dose co-administered with the morning final dose of Quinidine 300 mg taken at the same time under fasted conditions.

Drug: TERN-701; Drug: Quinidine

Interventions

TERN-701 DRUG

Oral Tablet

Also known as: MK-4208, HS-10382

Cohort 10: SAD Escalation of TERN-701 Dose Level 8; Cohort 11: SAD Escalation of TERN-701 Dose Level 9; Cohort 12: TERN-701 Dose Level 3 + Itraconazole 200 mg; Cohort 13: Multiple Ascending Dose (MAD) Escalation of TERN-701 Dose Level 4; Cohort 14: TERN-701 Dose Level 5 + Probe Substrate Cocktail-2; Cohort 15: TERN-701 Dose Level 8 + Probe Substrate Cocktail-2; Cohort 16: Food Effect on TERN-701 Dose Level 8 Formulations with Rabeprazole 20 mg; Cohort 17: Food Effect on TERN-701 Dose Level 8 Selected Formulation with Rabeprazole 20 mg; Cohort 18: TERN-701 Dose Level 8 + Bosentan 125 mg; Cohort 19: TERN-701 Dose Level 6 + Quinidine 300 mg; Cohort 1: Single Ascending Dose (SAD) Escalation of TERN-701 Dose Level 1; Cohort 2: SAD Escalation of TERN-701 Dose Level 2; Cohort 3: SAD Escalation of TERN-701 Dose Level 3 and Food Effect; Cohort 4: SAD Escalation of TERN-701 Dose Level 4; Cohort 5: SAD Escalation of TERN-701 Dose Level 5; Cohort 6: SAD Escalation of TERN-701 Dose Level 7; Cohort 7: TERN-701 Formulations with Rabeprazole 20 mg; Cohort 8: TERN-701 + Probe Substrate Cocktail-1; Cohort 9: TERN-701 Dose Level 5 + Rabeprazole 20 mg

Rabeprazole DRUG

The United States commercially marketed 20 mg oral tablet formulation is being used in this trial.

Cohort 16: Food Effect on TERN-701 Dose Level 8 Formulations with Rabeprazole 20 mg; Cohort 17: Food Effect on TERN-701 Dose Level 8 Selected Formulation with Rabeprazole 20 mg; Cohort 7: TERN-701 Formulations with Rabeprazole 20 mg; Cohort 9: TERN-701 Dose Level 5 + Rabeprazole 20 mg

Midazolam DRUG

2 mg oral syrup formulation administered as part of the probe substrate cocktail-1 and probe substrate cocktail-2. The United States commercially marketed formulation is being used in this trial.

Cohort 14: TERN-701 Dose Level 5 + Probe Substrate Cocktail-2; Cohort 15: TERN-701 Dose Level 8 + Probe Substrate Cocktail-2; Cohort 8: TERN-701 + Probe Substrate Cocktail-1

Digoxin DRUG

0.25 mg oral tablet formulation administered as part of the probe substrate cocktail-1. The United States commercially marketed formulation is being used in this trial.

Cohort 8: TERN-701 + Probe Substrate Cocktail-1

Pravastatin DRUG

40 mg oral tablet formulation administered as part of the probe substrate cocktail-1. The United States commercially marketed formulation is being used in this trial.

Cohort 8: TERN-701 + Probe Substrate Cocktail-1

Montelukast DRUG

10 mg oral tablet formulation administered as part of the probe substrate cocktail-1. The United States commercially marketed formulation is being used in this trial.

Cohort 8: TERN-701 + Probe Substrate Cocktail-1

Omeprazole DRUG

40 mg oral tablet formulation administered as part of the probe substrate cocktail-1. The United States commercially marketed formulation is being used in this trial.

Cohort 8: TERN-701 + Probe Substrate Cocktail-1

Itraconazole DRUG

The United States commercially marketed 200 mg oral capsule formulation is being used in this trial.

Cohort 12: TERN-701 Dose Level 3 + Itraconazole 200 mg

Warfarin DRUG

5 mg oral tablet formulation administered as part of the probe substrate cocktail-2. The United States commercially marketed formulation is being used in this trial.

Cohort 14: TERN-701 Dose Level 5 + Probe Substrate Cocktail-2; Cohort 15: TERN-701 Dose Level 8 + Probe Substrate Cocktail-2

Rosuvastatin DRUG

10 mg oral tablet formulation administered as part of the probe substrate cocktail-2. The United States commercially marketed formulation is being used in this trial.

Cohort 14: TERN-701 Dose Level 5 + Probe Substrate Cocktail-2; Cohort 15: TERN-701 Dose Level 8 + Probe Substrate Cocktail-2

Bosentan DRUG

The Europe commercially marketed 125 mg oral tablet formulation is being used in this trial.

Cohort 18: TERN-701 Dose Level 8 + Bosentan 125 mg

Quinidine DRUG

The United States commercially marketed 300 mg oral tablet formulation is being used in this trial.

Cohort 19: TERN-701 Dose Level 6 + Quinidine 300 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has body weight ≥48 kg (105.6 lbs) and body mass index within the range of 18.5 to 32 kg/m\^2 (inclusive)
• Is in good health

You may not qualify if:

• Has history or clinical manifestation of any metabolic, allergic, autoimmune, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, ocular, respiratory, endocrine, or psychiatric disorder, or any condition that would affect drug absorption, distribution, metabolism, or excretion (eg, stomach or intestinal surgery, or gallbladder removal/cholecystectomy). Uncomplicated appendectomy and hernia repair will be allowed.
• Has history of QT prolongation syndrome, unexplained syncope, family history of sudden death, atrial fibrillation, malignant tumor, mental disorder, or any major disease
• Has positive screening test for Hepatitis B surface antigen, anti-Hepatitis C virus antibodies, or anti-Human immunodeficiency virus (HIV) 1 and 2 antibodies
• Has any known history of bleeding, or prothrombin time (TERN-701 + Probe Substrate Cocktail-2 arm only)

Sponsors & Collaborators

• Terns, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (1)

ICON

Millcreek, Utah, 84124, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

Rabeprazole; Midazolam; Digoxin; Pravastatin; montelukast; Omeprazole; Itraconazole; Warfarin; Rosuvastatin Calcium; Bosentan; Quinidine

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzodiazepines; Benzazepines; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Piperazines; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Pyrimidines; Benzenesulfonamides; Benzene Derivatives; Cinchona Alkaloids; Alkaloids; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Quinolines

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2026
• First Posted: September 24, 2026
• Study Start: December 21, 2023
• Primary Completion: June 30, 2026
• Study Completion: June 30, 2026
• Last Updated: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)