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

NCT05057949 | Completed Phase 1

• 1 other identifier: Z650-DDI-104
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (2)

• Cmax

  Maximum Observed Plasma Concentration of Larotinib

  Day 1 pre-dose at multiple time points (up to 192 hours) post-dose

• AUC∞

  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 Outcomes (2)

• AUClast

  Day 1 pre-dose at multiple time points (up to 192 hours) post-dose

• Tmax

  Day 1 pre-dose at multiple time points (up to 192 hours) post-dose

Study Arms (2)

Part A, Treatment Sequence(Larotinib-Larotinib/Rifampin)

EXPERIMENTAL

Larotinib , capsules (150mg\*2+50mg\*1), at Hour 0 on Day 1 followed by an overnight fast. On Days 15 to 26, participants received rifampin 600 mg as capsules, orally, once daily (QD) and Larotinib 350 mg as capsules, orally was coadministered on Day 20. There was a washout period of 13 days between the two treatments.

Drug: Larotinib; Drug: Rifampin

Part B, Treatment Sequence(Larotinib-Larotinib/itraconazole)

EXPERIMENTAL

Larotinib , capsules (150mg\*2+50mg\*1), at Hour 0 on Day 1 followed by an overnight fast. On Days 15 to Day 25, participants received itraconazole 200 mg solution, orally, once daily (QD) on Days 15 to Day 25 and a single oral dose of Larotinib 350 mg as capsule was coadministered on Day 19 (Treatment B). There was a washout period of 13 days between the two treatments.

Drug: Larotinib; Drug: Itraconazole

Interventions

Larotinib DRUG

Larotinib Capsules

Also known as: Z650

Part A, Treatment Sequence(Larotinib-Larotinib/Rifampin); Part B, Treatment Sequence(Larotinib-Larotinib/itraconazole)

Rifampin DRUG

Rifampin Capsules

Also known as: Rifampin Capsules

Part A, Treatment Sequence(Larotinib-Larotinib/Rifampin)

Itraconazole DRUG

Itraconazole Capsules

Also known as: Itraconazole Capsules

Part B, Treatment Sequence(Larotinib-Larotinib/itraconazole)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The informed consent was signed before the study, and the content, process and possible adverse reactions of the study were fully understood;
• Without Plan for pregnancy or pregnant within 6 months from screening to the last dose of the study drug;
• Healthy, adult, male or female, 18 - 55 years of age;
• 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;
• Subjects, who are healthy, as having no clinically significant abnormalities in vital signs and physical examination.

You may not qualify if:

• Average daily smoking \>5 cigarettes in 3 months before the study;
• Known allergic reactions or hypersensitivity to any excipient of the study drug formulation(s).
• History of alcoholism(defined as Alcohol consumption of \> 14 units/week);
• Those with positive urine drug screening or those with a history of drug abuse or drug use in the past five years ;
• Blood donation or significant blood loss (\>450 mL) within 3 months prior to screening;
• 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;
• Have any medical condition that increases the risk of bleeding, such as hemorrhoids, acute gastritis, or stomach and duodenal ulcers ;
• Use of any prescription drugs, over-the-counter drugs, any vitamin products or herbal medicines in the 14 days prior to screening;
• Any drugs that changed the activity of liver drug enzymes, such as barbiturates and rifampicin, were taken within 30 days before screening;
• Have taken the following inhibitors or inducers of CYP3A4, CYP2C8, CYP2C19 and P-GP within 30 days before screening;
• 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 ;
• 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) ;
• Abnormal abdominal ultrasonography, chest radiography, ECG examination is clinically significant, or the corrected QT interval (QTcF) of ECG \>470ms during screening period ;
• Female subjects were lactating or had positive blood pregnancy results at screening or check in;
• 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;

Sponsors & Collaborators

• Sunshine Lake Pharma Co., Ltd.: lead

Study Sites (1)

First Hospital of Jilin University

Changchun, Jilin, 130000, China

Location

MeSH Terms

Interventions

Rifampin; Itraconazole

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Piperazines

Study Officials

• Yanhua Ding

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2021
• First Posted: September 27, 2021
• Study Start: November 24, 2021
• Primary Completion: February 17, 2022
• Study Completion: September 28, 2023
• Last Updated: May 18, 2025

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)