Drug-drug Interaction Study of XZP-3621 Tablet

A Drug-drug Interaction Study Evaluating the Pharmacokinetic Effects of Itraconazole or Rifampin or Esomeprazole on XZP-3621 Tablets in Healthy Subjects

This is an open-label, single center, 2 period, one sequence study to investigate the potential drug drug interaction between itraconazole or rifampin or esomeprazole and XZP-3621 tablet.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: XZP-3621 tablet and itraconazole oral liquid (for Arm1); Drug: XZP-3621 tablet and Rifampicin capsules (For Arm 2); Drug: XZP-3621 tablet and esomeprazole tablet (For Arm3)

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ninghua Zhu; Phone Number: +86-13910648041; Email: zhuninghua@xuanzhubio.com

Study Locations

• China
  • Shan Dong
    • Qingdao, Shan Dong, China
      • The Affiliated Hospital of Qingdao University
      • Contact: Yu Cao, Doctor; Phone Number: +86-0532-82911767; Email: caoyu1767@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male or female subjects aged 18-65 years (including boundary values);
2. Male weight ≥50kg, female weight ≥45kg, body mass index (bmi) in the range of 19-28 kg/m2 (including boundary value);
3. No mental abnormalities, cardiovascular system, nervous system, respiratory system, digestive system, urinary system, History of systemic, endocrine and metabolic abnormalities;
4. The subject and his/her partner agreed to use effective contraception and had no plans to donate sperm or eggs from the time of trial screening until 6 months after the last dose. Women of childbearing age must have a negative blood pregnancy test before the first dose;
5. The subjects should be able to communicate well with the researchers, understand and comply with the requirements of the study, and understand and sign the informed consent.

Exclusion Criteria:

• 1. Allergy (allergy to two or more substances) or known allergy to XZP-3621 or similar drugs (Group 1 (itraconazole group) excluded patients with history of allergy to itraconazole or similar drugs; group 2 (rifampicin group) excluded patients with allergy to rifampicin or its similar antibacterial drugs); The third group (esomeprazole group) excluded patients with esomeprazole or similar drug allergy history];

  2.During screening, there are clinical significant abnormal results in Physical examination, laboratory tests, 12-lead electrocardiogram, Anteroposterior and lateral chest x-ray examination or abdomen B ultrasound examination (including thyroid dysfunction with clinical significance)

  3. Frequent use of sedation, sleeping pills or other addictive drugs within 6 months before enrollment;

  4. Patients with a history of drug abuse or positive urine drug screening within 12 months before enrollment;

  5. Smokers who smoked more than 5 cigarettes per day in the 3 months before screening, or who could not stop using any tobacco products during the study;

  6. Alcohol breath test positive o regular drinkers within 6 months before enrollment, drinking more than 3 units per day, or more than 21 units of alcohol per week(1 unit is equivalent to a 350-ml bottle beer or 120 mL liquor or 30 mL spirits (above 50°)];

  7. Use any prescription drugs or traditional Chinese medicine within 4 weeks before enrollment, and/or use any OTC drugs or food supplements (including vitamins, calcium tablets, etc.) within 2 weeks before the first dose;

  8. Participated in other clinical trials and used investigational drugs within 3 months before enrollment;

  9. Those who received live vaccine within 2 weeks before the first dose, or planned to receive live vaccine during the study or within 7 days after the study was completed;

  10. Blood donation or blood loss of 400 mL within 3 months before enrollment, or blood transfusion; Blood donation (including component blood donation) or blood loss of 200 mL within 1 month before enrollment;

  11. Have a history of major disease or major surgery or trauma within 3 months before screening;

  12. Gastrointestinal disease causing clinically significant symptoms such as nausea, vomiting, diarrhea, or malabsorption syndrome, or a history of severe vomiting or diarrhea within one week before enrollment;

  13. Female subjects during pregnancy and lactation and female subjects of reproductive age who cannot take contraception as required;

  14. HBsAg, HCV Ab, Treponema pallidum antibody, HIV Ab test results are positive;

  15. Those who have special dietary requirements (including lactose intolerance) and are unable to comply with the provided diet and corresponding regulations;

  16. Subjects refused to discontinue any beverage or food containing xanthine derivatives, such as caffeine (coffee, tea, cola, chocolate, etc.) for 48 hours before the first dose and until the end of the study;

  17. Use of any drug that inhibits or induces hepatic metabolism (inducer) within 30 days prior to the first dose such as: barbiturates, carbamazepine, phenytoin sodium, rifamequine; Inhibitors such as cimetidine, Cyclosporine, macrolides, verapamil, quinolones, pyrroles, etc.);

  18. Use of proton pump inhibitor (PPI) drugs within 7 days before the first dose(eg: Rabeprazole, pantoprazole, esomeprazole, etc.).

  19. Ingested or planned ingestion of grapefruit or grapefruit-related citrus within 14 days before the first dose Fruit (such as lime, grapefruit), star fruit, papaya, pomegranate or above fruit products;

  20. Those who cannot tolerate blood collection by venipuncture or whose blood vessels are in poor condition;

  21. Other subjects deemed unsuitable to participate in the study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XZP-3621 tablet and itraconazole oral liquid	Drug: XZP-3621 tablet and itraconazole oral liquid (for Arm1); There are 2 periods, for the 1st period, the subjects will only take XZP-3621 tablets QD on Day1. For period 2,the subjects will take itraconazole from Day11 to Day13，they will take itraconazole in combinaiton with XZP-3621 on Day14，then take itraconazole only, from Day15 to Day27.
Experimental: XZP-3621 tablet and Rifampicin capsules	Drug: XZP-3621 tablet and Rifampicin capsules (For Arm 2); There are 2 periods, for the 1st period, the subjects will only take XZP-3621 tablets qd on Day1 . For period 2,the subjects will take Rifampicin from Day11 to Day17，they will take Rifampicin in combinaiton with XZP-3621 on day18，then take Rifampicin only, from Day19 to Day26.
Experimental: XZP-3621 tablet and esomeprazole tablet	Drug: XZP-3621 tablet and esomeprazole tablet (For Arm3); There are 2 periods, for the 1st period, the subjects will only take XZP-3621 tablets QD on Day1 . For period 2,the subjects will take esomeprazole from Day11 to Day 15，they will take esomeprazole in combinaiton with XZP-3621 on Day16.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration versus time curve of XZP-3621 and its metabolite in plasma (AUC) (Part 1a and Part1b)	To determine the AUC of XZP-3621 and its metabolite.	Up to nearly 1 month.
Maximum serum concentration (Cmax) of XZP-3621 and its metabolite.	To determine the maximum serum concentration (Cmax) of XZP-3621 and its metabolite.	Up to nearly 1 week.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of Maximum observed serum concentration (Tmax) of XZP-3621 and its metabolite .	To determine the Tmax of XZP-3621 and its metabolite.	Up to nearly 1 week.
Serum Half-life (T-HALF) of XZP-3621 and its metabolite .	To determine the t1/2 of XZP-3621 and its metabolite .	Up to nearly 1 week.
Number of patients with adverse events and serious adverse events.	Number of patients who experienced an adverse event or serious adverse events.	Up to nearly 2 months.
Severity of adverse events and serious adverse events.	Severity of the adverse events or serious adverse events.	Up to nearly 2 months.

Collaborators and Investigators

• Sponsor: Xuanzhu Biopharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Yu Cao, The Affiliated Hospital of Qingdao University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 15, 2022
• Primary Completion (Anticipated): April 5, 2023
• Study Completion (Anticipated): August 2, 2023

Study Registration Dates

• First Submitted: October 16, 2022
• First Submitted That Met QC Criteria: October 16, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole; Esomeprazole
• Other Study ID Numbers: XZP-3621-1003

Drug and device information, study documents

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