Clinical trial NCT05057949: A Study to Evaluate Drug-Drug Interaction of Larotinib With Itraconazole and Rifampin in Healthy Adult Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Sunshine Lake Pharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-27
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cmax
timeFrame: Day 1 pre-dose at multiple time points (up to 192 hours) post-dose
measure: AUC∞
timeFrame: Day 1 pre-dose at multiple time points (up to 192 hours) post-dose
Secondary outcomes:
measure: AUClast
timeFrame: Day 1 pre-dose at multiple time points (up to 192 hours) post-dose
measure: Tmax
timeFrame: Day 1 pre-dose at multiple time points (up to 192 hours) post-dose
Other outcomes:
Locations:
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
Study officials:
affiliation: The First Hospital of Jilin University
name: Yanhua Ding
role: PRINCIPAL_INVESTIGATOR
References: