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

Official title

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

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

• Drug MDR-001
  Oral small-molecule GLP-1 receptor agonist ;Investigational drug (not yet approved)
• Drug Rifampin
  Strong CYP3A4 inducer; Marketed anti-tuberculosis drug
• Drug Itraconazole
  Strong CYP3A4 inhibitor; Marketed antifungal drug

Primary outcome measures

• 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).]
• 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).]
• 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).]

Secondary outcome measures (12)

• Other Pharmacokinetic Parameters 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).]
• Other Pharmacokinetic Parameters 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).]
• Other Pharmacokinetic Parameters 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).]
• Other Pharmacokinetic Parameters 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).]
• Other Pharmacokinetic Parameters 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).]
• Other Pharmacokinetic Parameters 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).]
• Safety and Tolerability - Adverse Events [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Crossover

Masking

Open label

Primary purpose

Basic science

Study locations

China · 1 center

• The First Hospital of Jilin University — Changchun

Identifiers

NCT: NCT07550621 · MDR-001-CN-06

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗