Healthy Volunteers (HV)
Conditions
Keywords
MDR-001, GLP-1 receptor agonist, Drug-drug interaction (DDI), Rifampin, Itraconazole, CYP3A4 inducer, CYP3A4 inhibitor, Pharmacokinetics (PK), Healthy volunteers
Brief summary
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.
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.
Interventions
DRUGMDR-001
Oral small-molecule GLP-1 receptor agonist ;Investigational drug (not yet approved)
DRUGRifampin
Strong CYP3A4 inducer; Marketed anti-tuberculosis drug
DRUGItraconazole
Strong CYP3A4 inhibitor; Marketed antifungal drug
Sponsors
MindRank AI Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Fixed-sequence crossover design where each participant serves as their own control. The study consists of two independent, non-randomized, open-label parts: Part A and B. The design allows within-participant comparison of pharmacokinetic parameters (alone vs. combination) for each part independently.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of MDR-001 | 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). | Maximum observed plasma concentration of MDR-001 after single-dose administration alone and in combination with rifampin (Part A) or itraconazole (Part B). |
| AUC0-t of MDR-001 | 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). | Area under the plasma concentration-time curve from time zero to the last measurable concentration after single-dose administration alone and in combination. |
| AUC0-∞ of MDR-001 | 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). | Area under the plasma concentration-time curve from time zero extrapolated to infinity after single-dose administration alone and in combinatio |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Other Pharmacokinetic Parameters of MDR-001 | 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). | Tmax (time to reach Cmax) when administered alone vs. in combination. |
| Safety and Tolerability - Adverse Events | 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). | 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). |
| Safety and Tolerability - Clinical Laboratory 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. | Clinically significant changes from baseline in hematology parameters as measured by complete blood cell count with differential, |
| Safety and Tolerability - 12 Lead ECG | 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. | Changes from baseline in PR interval |
| Safety and Tolerability - 12-Lead ECG | 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. | Changes from baseline in QRS duration |
| Safety and Tolerability - Vital Signs | 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. | Changes from baseline in systolic and diastolic blood pressure |
| Safety and Tolerability - Physical Examination | Screening, Day -1, Day 3, co-administration day (Day 10 or 7), Day 12 or 9, and early termination. | Clinically significant abnormalities in general physical examination. |
Countries
China
Contacts
CONTACTGuodong Li, PhD
CONTACTAdam A. H. Baidoo, MD
PRINCIPAL_INVESTIGATORXiaojiao Li, MD
The First Hospital of Jilin University
Outcome results
None listed