Drug-Interaction Assessment of GSK3772701 in Healthy Male and Female Participants Aged 18 to 55 Years

A Phase 1, Open-Label Study in Healthy Participants Aged 18 to 55 Years to Investigate the CYP3A4 Interaction Potential of GSK3772701

This study aims to evaluate whether GSK3772701 alters the pharmacokinetics (PK) of midazolam (MDZ), a standard probe substrate for the CYP3A4 enzyme. The findings are planned to be used to determine whether GSK3772701 acts as an inducer and/or inhibitor of CYP3A4 and will help guide recommendations for safe co-administration with CYP3A4 substrates.

Study Overview

• Status: Not yet recruiting
• Conditions: Malaria, Falciparum
• Intervention / Treatment: Drug: Midazolam (MDZ); Drug: GSK3772701

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged 18 to 55 years (inclusive), at the time of signing the informed consent form (ICF).
2. Weight of at least 50 kg with a body-mass index <=18.0 and <=30.0 kg/m².
3. Written informed consent obtained from the participant prior to performance of any study specific procedure, and which includes agreement to compliance, with the requirements and restrictions listed in the ICF and in this protocol.
4. Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of study assessments, return for follow-up visits).

5. Participants who are healthy as established by medical evaluation including medical history, physical examination, cardiac monitoring, and clinical laboratory assessment before entering into the study.

   Contraception:

   • Male participants are eligible to participate.
   • A female participant is eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies:
6. Is a participant of non-childbearing potential (PONCBP). OR
7. Is a POCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, for 30 days prior to and during the study intervention period and for at least 7 days after the last dose of GSK3772701 and at least 2 days after the last dose of MDZ.
8. A POCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at Screening and within 24 hours before the first dose of study intervention.
9. A blood sample for simultaneous follicle-stimulating hormone (FSH) may be collected, and estradiol levels may be included at investigator's discretion to confirm non-reproductive potential when menopausal status is uncertain according to the local laboratory reference range.

Exclusion Criteria:

1. History or presence/significant history of or current cardiovascular, respiratory, hepatic, renal, urological, gastrointestinal, immunological, dermatological, endocrine, hematologic, neurological, or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
2. Any condition where the administration of MDZ could be contraindicated, including but not limited to, hypersensitivity (MDZ, any of its excipients, or to any benzodiazepines), sleep apnea, glaucoma (narrow-angle glaucoma, acute or open angle glaucoma, untreated), myasthenia gravis, respiratory insufficiency, impaired pulmonary function, or severe hepatic impairment.
3. History of any malignancy within the past 5 years. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy which is considered cured with minimal risk of recurrence. Participants under evaluation for possible malignancy are not eligible.
4. History of any reaction or hypersensitivity likely to be exacerbated by any component (formulation, capsule, or excipients) of the study intervention(s) (including hypromellose [hydroxypropyl methylcellulose] for GSK3772701) or allergies to cherries (as per MDZ USPI).
5. Acute or chronic clinically significant pulmonary, endocrinological, cardiovascular, muscular, neurological, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
6. Participants should have baseline clinical laboratory values (renal, hepatic, and hematological) within normal limits or clinically acceptable to the investigator. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, or outside the normal reference range for the population being studied, may be included only if the investigator considers that the finding is unlikely to introduce additional risk factors for the participant and will not interfere with the study procedures or endpoints.
7. Participants with supine blood pressure (BP) >=140 mm Hg (systolic) or >=90 mm Hg (diastolic).
8. Estimated glomerular filtration rate (eGFR) of <80 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2021).
9. The participant must agree to and adhere to the concomitant therapy (including non-drug therapies) restrictions from the Screening Visit through to the end of the study.
10. Any other clinical condition that, in the opinion of the investigator, might pose an additional risk to the participant due to participation in the study or would make adhering to study procedures for the duration of the study difficult.
11. Sensitivity to heparin or heparin-induced thrombocytopenia.
12. Past or intended use of over-the-counter or prescription medication (including herbal medications, vitamins and supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer), or 5 times the half-life (whichever is longer) prior to dosing.
13. Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) or investigational drugs or non-registered product (drug, vaccine, or medical device) within 3 months or 5 times the half-life (whichever is longer) prior to dosing.
14. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.

15. Current or prior enrolment in this or any other clinical study involving an investigational study intervention, or any other type of medical research, within the last 30 days or 5 half-lives, whichever is longer, prior to signing of the ICF.

    Participants who screen fail for the current study are not eligible for re-screening or enrollment.

16. Positive drug/alcohol screen, including tetrahydrocannabinol at Screening or Admission.
17. Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine containing products within 6 months prior to Screening.
18. Positive human immunodeficiency virus (HIV) antibody test.
19. Regular alcohol consumption within 6 months prior to the clinical study defined as: An average weekly alcohol intake of 14 units for males or 7 units for females. One unit is equivalent to 8 g of alcohol: a half-pint. (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.
20. Regular use of combustible tobacco products, and non-combustible nicotine delivery systems, inclusive of cigarettes, cigars, pipes, and materials used to "vape".
21. Participants who have lost or donated over 500 mL of blood within 90 days prior to enrollment or intend to donate blood or blood products during the study.
22. Participants who have donated plasma within 7 days prior to enrollment.
23. Any study personnel or their immediate dependents, family, or household members.
24. Regular use of known drugs of abuse, including tetrahydrocannabinol.

25. The following liver safety criteria are exclusionary:

    • Alanine aminotransferase (ALT) >1.5 × the upper limit of normal (ULN).
    • Total bilirubin >1.5 × ULN. Participants with Gilbert's syndrome can be included with total bilirubin >1.5 × ULN if direct bilirubin is <=1.5 × ULN.
    • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
    • Presence of hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) at Screening or within 3 months prior to first dose of study intervention.
    • Positive hepatitis C antibody test results at Screening or within 3 months prior to first dose of study intervention.
    • Positive hepatitis C RNA test results at Screening or within 3 months prior to first dose of study intervention.
26. QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 msec.
27. The participant has congenital long QT syndrome or known prolongation of the QTc interval.
28. The participant has a family history of QT prolongation or sudden death.
29. The participant has any current or previous history of episodes of symptomatic bradycardia or bradyarrhythmia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study participants; Healthy participants receive Midazolam (MDZ) on days 1, 3, 6 and 10, and GSK3772701 on days 3, 4 and 5.	Drug: Midazolam (MDZ); Participants receive MDZ orally.; Drug: GSK3772701; Participants receive GSK3772701 orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax) of MDZ	At 0 hours (h) (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Area under the concentration-time curve. from time 0 to the last measurable concentration [AUC(0-t)] of MDZ	At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Area under the plasma concentration-time curve from time 0 extrapolated to infinity [AUC(0-inf)] of MDZ	At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of 1-hydroxymidazolam (OH-MDZ)		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
AUC(0-t) of 1-OH-MDZ		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
AUC(0-inf) of 1-OH-MDZ		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Metabolite-to-parent ratios (1-OH-MDZ/MDZ) based on Cmax		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Metabolite-to-parent ratios (1-OH-MDZ/MDZ) based on AUC(0-t)		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Metabolite-to-parent ratios (1-OH-MDZ/MDZ) based on AUC(0-inf)		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Time to maximum observed concentration (Tmax) of MDZ and 1-OH-MDZ		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Terminal half-life (t1/2) of MDZ and 1-OH-MDZ		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Apparent oral plasma clearance (CL/F) of MDZ		At 0h (pre-dose) and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose for each MDZ administration on days 1, 3, 6 and 10
Cmax of GSK3772701		At 0h (pre-dose) and at 0.5, 1, 2, 3, 4, 6, 12, 20 and 24 hours post-dose on days 3 and 5
AUC(0-t) of GSK3772701		At 0h (pre-dose) and at 0.5, 1, 2, 3, 4, 6, 12, 20 and 24 hours post-dose on days 3 and 5
Area under the plasma concentration-time curve from time zero to 24 hours [AUC(0-24)] of GSK3772701		At 0h (pre-dose) and at 0.5, 1, 2, 3, 4, 6, 12, 20 and 24 hours post-dose on days 3 and 5
Tmax of GSK3772701		At 0h (pre-dose) and at 0.5, 1, 2, 3, 4, 6, 12, 20 and 24 hours post-dose on days 3 and 5
Concentration at 24 hours post dose (C24h) of GSK3772701		At Day 4 pre-dose (24 hours post Day 3 dose), Day 5 pre-dose (24 hours post Day 4 dose) and Day 6 (24 hours post Day 5 dose)
Incidence of adverse events (AEs) overall, by severity and relationship to GSK3772701	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. The severity of AEs is determined by the investigator using the Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading of Severity of Adult and Pediatric Adverse Events, corrected version 2.1. Grades are defined based on numeric criteria as follows Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: potentially life-threatening; Grade 5: death. Higher grades indicate greater severity. The incidence rate describes the rate at which an event occurs.	From Day 1 to Day 12
Incidence of serious adverse events (SAEs) overall, by severity and relationship to GSK3772701	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or extends existing hospitalization, causes persistent or significant disability/incapacity, involves a congenital anomaly/birth defect in a participants offspring, includes an abnormal pregnancy outcome, or occurs in any other situation per the investigators judgement. The severity of SAEs is determined by the investigator using the DAIDs Table for Grading of Severity of Adult and Pediatric Adverse Events, corrected version 2.1. Grades are defined based on numeric criteria as follows Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: potentially life-threatening; Grade 5: death. Higher grades indicate greater severity. The incidence rate describes the rate at which an event occurs.	From Day -30 to Day 12

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Estimated): June 26, 2026
• Primary Completion (Estimated): August 27, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: June 19, 2026
• First Submitted That Met QC Criteria: June 19, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy participants; Midazolam; Open label; CYP3A4; GSK3772701
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Malaria, Falciparum; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Midazolam
• Other Study ID Numbers: 300294

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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