Drug-Drug Interaction Study of MDR-001 With Rifampin and Itraconazole in Healthy Adult Participants

A Phase 1 Study to Evaluate the Effect of Rifampin on the Pharmacokinetics of MDR-001 and the Effect of Itraconazole on the Pharmacokinetics of MDR-001 in Healthy Adult Study Participants

A Phase I, open-label, fixed-sequence, two-part drug-drug interaction study in healthy Chinese adults to evaluate the effect of multiple-dose rifampin (Part A) or itraconazole (Part B) on the single-dose pharmacokinetics of MDR-001, an oral GLP-1 receptor agonist.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers (HV)
• Intervention / Treatment: Drug: MDR-001; Drug: Rifampin; Drug: Itraconazole

Detailed Description

This phase 1, single-center, open-label, fixed-sequence drug-drug interaction study will evaluate the effect of multiple-dose rifampicin (a strong CYP3A4 inducer) and multiple-dose itraconazole (a strong CYP3A4 inhibitor) on the single-dose pharmacokinetics of MDR-001, an oral small-molecule GLP-1 receptor agonist being developed for weight management. The study plans to enroll 28 healthy Chinese adults (18-55 years, BMI 18-28 kg/m²), with 12 participants in Part A (rifampicin) and 16 in Part B (itraconazole). The primary outcomes are the effects of rifampicin and itraconazole on Cmax, AUC0-t, and AUC0-∞ of MDR-001. Secondary outcomes include safety and tolerability (adverse events, vital signs, ECG, laboratory tests) and comparison of other pharmacokinetic parameters (Tmax, t1/2, MRT, CL/F, Vd/F, λz) between MDR-001 alone and combined with the interacting drugs.

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

Contacts and Locations

• Study Contact: Name: Guodong Li, PhD; Phone Number: +8618968027256; Email: guodong.li@mindrank.cn
• Study Contact Backup: Name: Adam A. H. Baidoo, MD; Phone Number: +8615658610670; Email: adam@mindrank.cn

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
      • Contact: Xiaojiao Li, MD; Phone Number: +8613514314089; Email: xingxingsuo12345@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Voluntary participation and signed informed consent before any study procedures, with full understanding of the study content, procedures, and potential adverse reactions.
• Healthy Chinese adult males or females aged 18 to 55 years (inclusive).
• Body weight ≥50 kg for males and ≥45 kg for females, and body mass index (BMI) between 18 and 28 kg/m² (inclusive).
• Judged by the investigator to be in good health, with medical history, laboratory tests, physical examination, vital signs, and ECG results being normal or abnormal without clinical significance.
• Participants and their partners must have no pregnancy plan and agree to use effective non-drug contraceptive measures (e.g., condoms, non-medicated intrauterine devices) from 2 weeks before screening until 6 months after the end of the study, unless permanent sterilization has been performed (e.g., bilateral tubal ligation, vasectomy).
• Willing to comply with the visit schedule, study treatment, laboratory tests, and other study-related procedures and requirements as specified in the protocol.

Exclusion Criteria:

• Average daily smoking >5 cigarettes within 3 months before dosing.
• History of headaches (e.g., migraine, tension-type headache).
• Allergic constitution (multiple drug or food allergies) or intolerance/allergy to the active ingredient or excipients of the study drugs.
• History of alcohol abuse (≥14 units of alcohol per week; 1 unit = 285 mL beer, 25 mL spirits, or 100 mL wine).
• History of drug abuse or use of illicit drugs within 5 years before dosing.
• Blood donation or significant blood loss (≥400 mL) within 3 months before dosing, or planned blood donation during the study.
• Any disease that increases bleeding risk, such as acute gastritis or gastric/duodenal ulcer.
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2), or genetic conditions predisposing to MTC.
• History of pancreatitis or symptomatic gallbladder disease.
• Serum calcitonin > upper limit of normal (ULN) at screening.
• Dysphagia, or gastrointestinal disorders affecting absorption (e.g., diarrhea, vomiting, inflammatory bowel disease, active ulcer), or history of gastrointestinal surgery leading to malabsorption, or long-term use of drugs affecting gastrointestinal motility (e.g., bariatric surgery such as gastric banding).
• Special dietary requirements and unable to accept standardized meals.
• Surgery within 3 months before dosing, or planned surgery during the study, or surgery that affects drug absorption, distribution, metabolism, or excretion.
• Received live attenuated vaccine within 1 month before dosing, or planned vaccination during the study.
• Use of any prescription drug, over-the-counter drug, vitamin product, or herbal medicine within 14 days before dosing.
• Significant changes in diet or exercise habits within 3 months before dosing.
• Use of CYP3A4 inhibitors, CYP3A4 inducers, or P-gp inhibitors within 14 days before the first dose, or planned use during the study.
• Participation in another clinical trial or receipt of an investigational drug within 3 months before dosing (unless the participant withdrew before treatment/randomization).
• ECG abnormalities with clinical significance at screening; QTcF >450 msec (males) or >470 msec (females) by Fridericia's correction.
• Pregnant, lactating, or positive pregnancy test in females of childbearing potential.
• Clinically significant laboratory abnormalities, or clinically significant diseases within 12 months before dosing (respiratory, circulatory, digestive, endocrine, rheumatic/immune, nervous, hematologic, or psychiatric disorders) that make the participant unsuitable for the study.
• Positive screening for hepatitis B surface antigen, hepatitis C antibody/core antigen, HIV antibody, or syphilis antibody.
• Acute illness or concomitant medication between screening and first dose.
• Positive alcohol breath test or urine drug screen.
• Any other condition judged by the investigator as unsuitable for participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (Rifampin Arm); Participants receive a single oral dose of MDR-001 alone on Day 1. then rifampin from Day 3 to Day 11, with a second single dose of MDR-001 co-administered on Day 10.	Drug: MDR-001; Oral small-molecule GLP-1 receptor agonist ;Investigational drug (not yet approved); Drug: Rifampin; Strong CYP3A4 inducer; Marketed anti-tuberculosis drug
Experimental: Part B (Itraconazole Arm); Participants receive a single oral dose of MDR-001alone on Day 1. , then receive itraconazole once daily from Day 3 to Day 8, with a second single dose of MDR-001 co-administered on Day 7.	Drug: MDR-001; Oral small-molecule GLP-1 receptor agonist ;Investigational drug (not yet approved); Drug: Itraconazole; Strong CYP3A4 inhibitor; Marketed antifungal drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of MDR-001	Maximum observed plasma concentration of MDR-001 after single-dose administration alone and in combination with rifampin (Part A) or itraconazole (Part B).	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
AUC0-t of MDR-001	Area under the plasma concentration-time curve from time zero to the last measurable concentration after single-dose administration alone and in combination.	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
AUC0-∞ of MDR-001	Area under the plasma concentration-time curve from time zero extrapolated to infinity after single-dose administration alone and in combinatio	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other Pharmacokinetic Parameters of MDR-001	Tmax (time to reach Cmax) when administered alone vs. in combination.	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Other Pharmacokinetic Parameters of MDR-001	t1/2 (terminal elimination half-life) when administered alone vs. in combination.	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Other Pharmacokinetic Parameters of MDR-001	MRT (mean residence time) when administered alone vs. in combination.	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Other Pharmacokinetic Parameters of MDR-001	CL/F (apparent clearance) when administered alone vs. in combination.	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Other Pharmacokinetic Parameters of MDR-001	Vd/F (apparent volume of distribution) when administered alone vs. in combination.	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Other Pharmacokinetic Parameters of MDR-001	λz (terminal elimination rate constant) when administered alone vs. in combination.	Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Safety and Tolerability - Adverse Events	Incidence, severity, and causality of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESI: grade ≥2 gastrointestinal events, grade 3 hypoglycemia, acute pancreatitis, thyroid C-cell tumors).	From first dose of study drug (Day 1) through follow-up phone call (Day 19 ±2 for Part A, Day 16 ±2 for Part B).
Safety and Tolerability - Clinical Laboratory Tests	Clinically significant changes from baseline in hematology parameters as measured by complete blood cell count with differential,	Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.
Safety and Tolerability - Clinical Laboratory Tests	Clinically significant changes from baseline in serum chemistry tests	Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.
Safety and Tolerability - Clinical Laboratory Tests	Clinically significant changes from baseline in coagulation tests.	Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.
Safety and Tolerability - Clinical Laboratory Tests	Clinically significant changes from baseline in urinalysis	Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.
Safety and Tolerability - Clinical Laboratory Tests	Clinically significant changes from baseline in thyroid function tests.	Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.
Safety and Tolerability - 12 Lead ECG	Changes from baseline in PR interval	Screening, Day -1, Day 1 (pre-dose and 2h post-dose), Day 3, Day 6 (Part A), Day 10 or 7 (pre-dose and 2h post-dose), Day 12 or 9, and early termination.
Safety and Tolerability - 12-Lead ECG	Changes from baseline in QRS duration	Screening, Day -1, Day 1 (pre-dose and 2h post-dose), Day 3, Day 6 (Part A), Day 10/7 (pre-dose and 2h post-dose), Day 12/9, and early termination.
Safety and Tolerability - 12 Lead ECG	Changes from baseline in QT interval	Screening, Day -1, Day 1 (pre-dose and 2h post-dose), Day 3, Day 6 (Part A), Day 10 or 7 (pre-dose and 2h post-dose), Day 12 or 9, and early termination.
Safety and Tolerability - 12 Lead ECG	Changes from baseline in QTcF interval.	Screening, Day -1, Day 1 (pre-dose and 2h post-dose), Day 3, Day 6 (Part A), Day 10 or 7 (pre-dose and 2h post-dose), Day 12 or 9, and early termination.
Safety and Tolerability - 12 Lead ECG	Changes from baseline in heart rate.	Screening, Day -1, Day 1 (pre-dose and 2h post-dose), Day 3, Day 6 (Part A), Day 10 or 7 (pre-dose and 2h post-dose), Day 12 or 9, and early termination.
Safety and Tolerability - Vital Signs	Changes from baseline in systolic and diastolic blood pressure	Screening, Day -1, Day 1 and co-administration day (pre-dose, 2h and 6h post-dose), Day 2, Day 3-9 or 11 (daily), Day 12 or 9, and early termination.
Safety and Tolerability - Vital Signs	Changes from baseline in pulse rate.	Screening, Day -1, Day 1 and co-administration day (pre-dose, 2h and 6h post-dose), Day 2, Day 3-9 or 11 (daily), Day 12 or 9, and early termination.
Safety and Tolerability - Vital Signs	Changes from baseline in body temperature.	Screening, Day -1, Day 1 and co-administration day (pre-dose, 2h and 6h post-dose), Day 2, Day 3-9 or 11 (daily), Day 12 or 9, and early termination.
Safety and Tolerability - Physical Examination	Clinically significant abnormalities in general physical examination.	Screening, Day -1, Day 3, co-administration day (Day 10 or 7), Day 12 or 9, and early termination.

Collaborators and Investigators

• Sponsor: MindRank AI Ltd
• Investigators: Principal Investigator: Xiaojiao Li, MD, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Estimated): May 6, 2026
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): June 8, 2026

Study Registration Dates

• First Submitted: April 11, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Healthy volunteers; Itraconazole; Rifampin; GLP-1 receptor agonist; Drug-drug interaction (DDI); Pharmacokinetics (PK); CYP3A4 inhibitor; CYP3A4 inducer; MDR-001
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Azoles; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Triazoles; Piperazines; Rifampin; Itraconazole
• Other Study ID Numbers: MDR-001-CN-06

Drug and device information, study documents

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