The Effect of Itraconazole and Rifampicin on the Pharmacokinetics of SH-1028

A Single-center, Open-label, Drug-drug Interaction Study of SH-1028 Tablets in Healthy Subjects

This is a phase I study to assess the drug-drug interaction of SH-1028 tablets and Itraconazole/Rifampicin tablets. The study also evaluates the pharmacokinetic and tolerability of SH-1028 tablets in healthy subjects. This study provides evidence for the designing of following clinical trial protocols.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Male Volunteers
• Intervention / Treatment: Drug: SH-1028; Drug: Itraconazole; Drug: Rifampicin

Detailed Description

A total of 40 evaluable healthy male subjects will be enrolled in this study.The subjects will be divided into two groups, A and B, with 20 people in each group.

In the itraconazole study (Group A), patients received single-dose SH-1028 200 mg on Days 1 and 12 and itraconazole(200 mg twice daily) on Days 8-14 orally.

In the rifampicin study (Group B), patients received SH-1028 200mg once daily on Days 1 and 14 and rifampicin 600 mg once daily on Days 8-16.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Huan Zhou, Ph D; Phone Number: 13665527160; Email: zhouhuan@bbmc.edu.cn

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • the First Affiliated Hospital with Bengbu Medical College
      • Contact: Huan Zhou, Ph D; Phone Number: 13665527160; Email: zhouhuan@bbmc.edu.cn
      • Principal Investigator: Huan Zhou, Ph D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male volunteers between the age of 18 to 45 years old (including 18 and 45 years old)
2. Body weight between 50.0 and 80.0 kg, Body mass index between 19.0 and 26.0 kg/m2 (including 19.0 and 26.0 kg/m2);
3. Normal physical findings, clinical laboratory values, vital signs and 12-lead ECG, or any abnormality that is non-clinically significant;
4. Promise not to smoke, drink alcohol or drink caffeinated beverages during the trial;
5. Be able to communicate well with the researcher and be able to complete the trial in accordance with the program.
6. Male subjects of reproductive potential with partners will be instructed to,and must be willing to practice a highly effective method of birth control for the duration of the study and continuing 6 months after discontinuing treatment with the investigational product.

Exclusion Criteria:

1. History of or current clinically significant cardio, pulmonary, endocrine, metabolism, renal, hepatic, gastrointestinal, dermatology, infection, hematology, neurological, mental disease or disorder. Or any other disease or physiological condition that may affect the results of the study;
2. Those who have undergone surgery within the first 3 months of the screening period, or who plan to undergo surgery during the study period, or who have previously undergone surgery that may affect drug absorption, distribution, metabolism, and excretion;
3. Subjects with dysphagia or have history of gastrointestinal disorders which affects study drug absorption;
4. Alcohol breath test results greater than 0.0mg/100mL.
5. Urine drug screening (morphine, methamphetamine, ketamine, dimethyldioxyamphetamine, tetrahydrocannabinol) positive;
6. Those who had received the vaccine within 28 days prior to screening, or who planned to receive the vaccine during the trial;
7. Positive test for HBs-Ag, HCV-Ab, HIV-Ab, or syphilis antibody;
8. Allergies, have allergies to drugs or foods; or have known allergies to the components of the investigated drug;
9. Those who smoked daily >5 sticks of cigarette, or the weekly alcohol consumption was higher than 14 units of alcohol (1 unit=10ml or 8g absolute alcohol. 25 ml 40% liquor, 330ml 5% beers, 175ml 12% grape wine are equal to 1.0, 1.5 and 2.0 units of alcohol respectively), or the history of drug abuse and drug abuseor 3 months prior to screening period;
10. Subjects with history of blood donation or massive blood loss (> 200 mL) within 3 months prior to screening;
11. Participated in other clinical trials within 3 months before screening;
12. Use of any drugs that alter liver enzyme activity within 28 days prior to screening;
13. Do not promise not to smoke, not drink alcoholic food or beverages, not consume xanthine-rich foods, not consume grapefruit, dragon fruit, mango, lime, carambola or other products within 24 hours before taking the study drug. Prepared foods or beverages, as well as chocolate, tea, coffee or cola and other special diets that affect the absorption, distribution, metabolism and excretion of drugs;
14. People who have used any medicine (including Chinese herbal medicine and health care products) within two weeks before taking the test drug;
15. History of syncope / needle syncope and intolerable intravenous indwelling needle;
16. Those who have special requirements for diet and cannot follow a unified diet;
17. hose who cannot complete this study because of other reasons, or any factors judged by investigator that the participants cannot meet.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole and SH-1028; In the itraconazole study, patients received single-dose SH-1028 200 mg on Days 1 and 12 and itraconazole(200 mg twice daily) on Days 8-14 orally.	Drug: SH-1028; tablet, oral, 200 mg once daily for day 1 and day 12; Drug: Itraconazole; capsule, oral, 200 mg twice daily for day 8 to day 14
Experimental: Rifampicin and SH-1028; In the rifampicin study, patients received SH-1028 200mg once daily on Days 1 and 14 and rifampicin 600 mg once daily on Days 8-16	Drug: SH-1028; tablet, oral, 200 mg once daily for day 1 and day 12; Drug: Rifampicin; capsule, oral, 600 mg once daily for day 8 to day 16

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Pharmacokinetics of SH-1028 by assessment of maximum plasma concentration	Blood samples collected on Day 1 and Day 12 (arm 1)/Day 14 (arm 2) at pre-dose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 96 hours post SH-1028 dose
AUC(0-last)	Pharmacokinetics of SH-1028 by assessment of area under the plasma concentration time curve from zero to last assessed timepoint	Blood samples collected on Day 1 and Day 12 (arm 1)/Day 14 (arm 2) at pre-dose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 96 hours post SH-1028 dose
AUC(0-∞)	Pharmacokinetics of SH-1028 by assessment of area under the concentration time curve from time 0 to infinity	Blood samples collected on Day 1 and Day 12 (arm 1)/Day 14 (arm 2) at pre-dose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 96 hours post SH-1028 dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Safety and tolerability	Up to 10 days after last dose

Collaborators and Investigators

• Sponsor: Nanjing Sanhome Pharmaceutical, Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 6, 2021
• Primary Completion (Anticipated): June 10, 2021
• Study Completion (Anticipated): June 30, 2021

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: March 18, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

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; 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: SHC013-I-05

Drug and device information, study documents

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