A Study to Evaluate Drug-Drug Interaction of Larotinib With Itraconazole and Rifampin in Healthy Adult Participants

Healthy Volunteers Clinical Trial

— Z650  

Official title:

A Single-center, Open, Self-controlled Design Clinical Study to Evaluate the Pharmacokinetic Effects of Rifampicin or Itraconazole on Single-dose Laolotinib Mesylate Capsules in Healthy Subjects

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05057949
• Other study ID #: Z650-DDI-104
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 24, 2021
• Est. completion date: March 21, 2023

Study information

• Verified date: October 2022
• Source: Sunshine Lake Pharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to characterize the effect of rifampin (Part A) and itraconazole(Part B) on the single-dose pharmacokinetics (PK) of Larotinib in healthy adult participants.

Description:

The drug being tested in this study is called Larotinib (Z650). The study assessed the drug-drug interaction of Larotinib with either a strong cytochrome P-450 (CYP)3A inducer, rifampin (Part A) , or with a strong CYP3A inhibitor itraconazole (Part B) in healthy adult participants.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: March 21, 2023
• Est. primary completion date: January 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. The informed consent was signed before the study, and the content, process and possible adverse reactions of the study were fully understood;

2. Without Plan for pregnancy or pregnant within 6 months from screening to the last dose of the study drug;

3. Healthy, adult, male or female, 18 - 55 years of age;

4. Male subjects should weigh at least 50 kg and female subjects should weigh at least 45 kg. Body mass index (BMI) =18.0 and =28.0 kg/m2;

5. Subjects, who are healthy, as having no clinically significant abnormalities in vital signs and physical examination.

Exclusion Criteria:

1. Average daily smoking >5 cigarettes in 3 months before the study;

2. Known allergic reactions or hypersensitivity to any excipient of the study drug formulation(s).

3. History of alcoholism(defined as Alcohol consumption of > 14 units/week);

4. Those with positive urine drug screening or those with a history of drug abuse or drug use in the past five years ;

5. Blood donation or significant blood loss (>450 mL) within 3 months prior to screening;

6. Have dysphagia or have gastrointestinal, liver, or kidney disease (whether cured or not) that affects drug absorption or excretion within 6 months prior to screening;

7. Have any medical condition that increases the risk of bleeding, such as hemorrhoids, acute gastritis, or stomach and duodenal ulcers ;

8. Use of any prescription drugs, over-the-counter drugs, any vitamin products or herbal medicines in the 14 days prior to screening;

9. Any drugs that changed the activity of liver drug enzymes, such as barbiturates and rifampicin, were taken within 30 days before screening;

10. Have taken the following inhibitors or inducers of CYP3A4, CYP2C8, CYP2C19 and P-GP within 30 days before screening;

11. Patients who had taken special diet (including pitaya, mango, grapefruit, etc.) or had strenuous exercise, or had other factors affecting drug absorption, distribution, metabolism and excretion, as judged by the researcher, within 14 days before screening ;

12. Participants who have participated in any drug clinical trials within 3 months prior to screening and have used the test drug (subjects may be enrolled in the study if they dropped out of the study prior to dosing, i.e., were not randomized or received dosing) ;

13. Abnormal abdominal ultrasonography, chest radiography, ECG examination is clinically significant, or the corrected QT interval (QTcF) of ECG >470ms during screening period ;

14. Female subjects were lactating or had positive blood pregnancy results at screening or check in;

15. Laboratory examination is abnormal and clinically significant, or the following diseases (including but not limited to gastrointestinal, renal, liver, neurological, hematological, endocrine, tumor, lung, immune, psychiatric or cardiovascular and cerebrovascular diseases) are clinically significant as found within 12 months prior to screening;

16. Viral hepatitis (including hepatitis B and C), HIV antigen/antibody or treponema pallidum antibody was positive at screening;

17. Acute illness or concomitant medication was occurred from the screening to the first administration of the experimental drug;

18. Subjects who consume chocolate, any food or drink containing caffeine or rich in xanthine within 24 hours before taking the study drug;

19. Alcohol breath test is positive at check-in.

20. Subjects who received vaccination within 28 days prior to screening or who plan to receive vaccination during the trial ;

21. The investigator deemed the subject unsuitable for this study for any reason

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Larotinib
Larotinib Capsules
• Rifampin
Rifampin Capsules
• Itraconazole
Itraconazole Capsules

Locations

Country	Name	City	State
China	First Hospital of Jilin University	Changchun	Jilin

Sponsors (1)

Lead Sponsor	Collaborator
Sunshine Lake Pharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax	Maximum Observed Plasma Concentration of Larotinib	Day 1 pre-dose at multiple time points (up to 192 hours) post-dose
Primary	AUC8	Area Under the Plasma Concentration-time Curve from Time 0 to Infinity, calculated using the observed value of the last quantifiable concentration for Larotinib	Day 1 pre-dose at multiple time points (up to 192 hours) post-dose
Secondary	AUClast	Area Under the Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Larotinib	Day 1 pre-dose at multiple time points (up to 192 hours) post-dose
Secondary	Tmax	Time to Reach the Maximum Plasma Concentration (Cmax) for Larotinib	Day 1 pre-dose at multiple time points (up to 192 hours) post-dose