A Study to Evaluate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of SY-5007 in Healthy Subjects

A Randomized, Open-label, Two-period, Self-controlled Study to Evaluate the Effect of Oral Rifampicin or Itraconazole on the Pharmacokinetics of SY-5007 Tablets in Healthy Subjects

This study is a single-center, open-lable and fixed sequence test conducted in healthy subjects to evaluate the pharmacokinetic effects of Itraconazole and Rifampicin on a single dose of SY-5007 Oral administration. It is planned to enroll 28 healthy subjects and assign them to two parallel test groups, Group A (SY-5007 combined with Itraconazole) and Group B (SY-5007 combined with Rifampicin).

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: SY-5007; Drug: Itraconazole; Drug: SY-5007; Drug: Rifampin

Detailed Description

A total of 28 evaluable healthy male subjects will be enrolled in this study. The subjects will be divided into two groups, A and B, with 14 people in each group.

In the itraconazole study (Group A), patients received single-dose SY-5007 80 mg on Day 1 and Day 11 and itraconazole 200 mg once or twice daily on Day 8-Day 18 orally.

In the rifampicin study (Group B), patients received single-dose SY-5007 160mg on Day 1 and Day 16 and rifampicin 600 mg once daily on Day 8-Day 21 orally.

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

Contacts and Locations

• Study Contact: Name: Yinghui Sun, Dr; Phone Number: 86-10-88858616; Email: yhsun@centaurusbio.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
      • Contact: Li Zheng; Phone Number: 86-28-85423655; Email: zhengli@wchscu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:

1. Fully understand the purpose, nature, methods, and potential adverse reactions of the trial, voluntarily participate, and sign a written informed consent form (ICF), and be able to follow the protocol requirements to complete the study as healthy subjects.
2. Male subjects aged ≥18 and ≤45 years old (including boundary values, based on the time of signing the informed consent form).
3. Body weight ≥50kg, and body mass index (BMI = weight/height^2, kg/m^2) between 18 and 26 kg/m^2 (including boundary values).
4. Qualified subjects of reproductive capability must agree with their sexual partners to adopt a medically accepted contraceptive measure (such as intrauterine device, contraceptive pills, or condoms) during the trial and for 3 months after the end of the trial, and have no plans to donate sperm/eggs during the trial and for 3 months after the end of the trial.

Exclusion Criteria:

Subjects will be ineligible for this study if they meet any of the following criteria:

1. Clear history of severe allergies, non-allergic drug reactions, or multiple drug allergies, or known hypersensitivity reactions to the investigational drug (active pharmaceutical ingredient or excipients).
2. Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen, hepatitis C antibodies, or syphilis treponema antibodies at screening.
3. Presence of clinically significant abnormal vital signs, physical examination findings, laboratory test results, or electrocardiogram results at screening.
4. Currently suffering from or known by the investigator to have chronic gastrointestinal, liver, or kidney diseases that may affect trial outcomes.
5. Symptoms or medical history of any major diseases, including but not limited to cardiovascular, hepatic, renal diseases, or other acute or chronic gastrointestinal diseases, respiratory diseases, musculoskeletal diseases, as well as diseases of the blood, endocrine, nervous, or psychiatric systems, or any other conditions or physiological states that may interfere with trial results.
6. Any surgical conditions or conditions that may significantly affect drug absorption, distribution, metabolism, and excretion, or any surgical conditions or conditions that may pose harm to subjects participating in the trial, such as a history of gastrointestinal surgery (gastrectomy, gastrojejunal anastomosis, intestinal resection, etc.), urinary tract obstruction or difficulty in urination, history of digestive tract ulcers, gastrointestinal bleeding, etc. (Subjects who have undergone appendectomy or hernia repair surgery can be enrolled in the study).
7. Known or suspected history of drug abuse within the past two years at screening, or drug abuse within the past three months at screening or baseline, or positive drug abuse screening during screening or baseline.
8. Underwent major surgery within the past six months before the first dose or planning to undergo surgery during the trial.
9. Smoked an average of more than 5 cigarettes per day within the past three months before the first dose or unwilling to stop using any tobacco products during the trial.
10. Regularly consumed alcohol within the past three months before the first dose (defined as consuming more than 14 units of alcohol per week, with 1 unit equal to 360 mL of beer with an alcohol content of 5%, or 45 mL of spirits with an alcohol content of 40%, or 150 mL of wine with an alcohol content of 12%), or unable to stop drinking during the trial, or positive alcohol breath test at screening.
11. History of blood donation or significant blood loss (≥300 mL) within the past two years before the first dose, or use of blood products or receiving blood transfusions within the past month before the first dose.
12. Participated in other drug or medical device clinical trials within the past three months before the first dose (excluding those screened but ultimately not enrolled), or used the study drug before.
13. Received vaccination or inactivated vaccines within the past month before the first dose.
14. Used any prescription drugs, non-prescription drugs, health products, or herbal medicines within the past two weeks before the first dose (if the half-life (t1/2) of the drug used can be confirmed, the washout period should be ≥5 t1/2, with the longer one taken).
15. Habitually consumed grapefruit juice or excessive amounts (more than 8 cups, 1 cup = 250 mL) of tea, coffee, and/or caffeinated beverages and unable to stop drinking for at least 48 hours before the first dose and during the trial.
16. Have special dietary requirements or difficulty swallowing.
17. Difficulty in blood sampling, or a history of fainting or intolerance to venipuncture.
18. Clear history of neurological or psychiatric disorders, including dementia or epilepsy, etc.
19. Diagnosis of malignant tumors within the past five years (excluding cured in situ cancers, such as non-melanoma skin cancers).
20. For scientific reasons, compliance reasons, or for the safety of the subjects, the investigator deems it inappropriate for the subject to participate in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A, Treatment Sequence (SY-5007-SY-5007/Itraconazole); SY-5007 80mg, tablets, once daily on Day 1 and Day 11 before meal; Itraconazole 200mg, once or twice daily from Day 8 to Day 18.	Drug: SY-5007; SY-5007 80 mg, Tablets, 2 discrete single doses at Day 1 and Day 11; Drug: Itraconazole; Itraconazole 200 mg, Capsules, Day 8-Day 18; Drug: SY-5007; SY-5007 160 mg, Tablets, 2 discrete single doses at Day 1 and Day 16
Experimental: Group B, Treatment Sequence (SY-5007-SY-5007/Rifampin); SY-5007 160mg, tablets, once daily on Day 1 and Day 16 before meal, Rifampicin 600mg, once daily from Day 8 to Day 21.	Drug: SY-5007; SY-5007 80 mg, Tablets, 2 discrete single doses at Day 1 and Day 11; Drug: SY-5007; SY-5007 160 mg, Tablets, 2 discrete single doses at Day 1 and Day 16; Drug: Rifampin; Rifampin 600 mg, Capsules, Day 8-Day 21

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax for SY-5007	Defined as maximum observed plasma concentration	Day 1-Day 22
Tmax for SY-5007	Defined as time to maximum plasma concentration	Day 1-Day 22
AUC0-t for SY-5007	Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration	Day 1-Day 22
AUC0-∞ for SY-5007	Defined as area under the single-dose plasma concentration-time curve from Hour 0 to infinity	Day 1-Day 22
t½ for SY-5007	Defined as apparent plasma terminal phase disposition half-life	Day 1-Day 22
CL/F for SY-5007	Defined as apparent total body clearance	Day 1-Day 22
Vz/F for SY-5007	Defined as apparent oral Volume of distribution	Day 1-Day 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of SY-5007	AE (adverse event) will be summarized by type and severity	Up to 29 days

Collaborators and Investigators

• Sponsor: Shouyao Holdings (Beijing) Co. LTD
• Investigators: Study Director: Yinghui Sun, Shouyao Holdings (Beijing) Co. LTD

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Itraconazole; Rifampin; SY-5007 tablets; Drug-drug Interaction Study
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; 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; 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
• Other Study ID Numbers: SY-5007-I-03

Drug and device information, study documents

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