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
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- MindRank AI Ltd
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Cmax of MDR-001
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts 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.
Arms & Interventions
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.
Intervention: MDR-001 (Drug)
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.
Intervention: Rifampin (Drug)
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.
Intervention: MDR-001 (Drug)
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.
Intervention: Itraconazole (Drug)
Outcomes
Primary Outcomes
Cmax of MDR-001
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- 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).)
- 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).)
- 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.)
- 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.)
- 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.)
- 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.)
- Safety and Tolerability - Physical Examination(Screening, Day -1, Day 3, co-administration day (Day 10 or 7), Day 12 or 9, and early termination.)