A Drug-drug Interaction Trial to Evaluate the Pharmacokinetics Effect of Rifampicin on Famitinib

A Single Center, Single Arm, Open and Fixed Sequence Study to Investigate the Pharmacokinetic Effects of Rifampicin on Famitinib in Healthy Male Subjects

The primary objective of the study was to assess the effect of repeated oral doses of Rifampicin on the pharmacokinetic profile of a single dose of Famitinib.

The secondary objective of the study was to assess the safety of Famitinib given alone versus Famitinib co-administered with Rifampicin.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Subjects
• Intervention / Treatment: Drug: Famitinib capsule; Drug: Rifampicin capsule

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Qingdao, Shandong, China, 266055
      • Affiliated Hospital of Qingdao University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male subjects aged 18 to 50 years old at the date of signing the informed consent;
2. Male body weight ≥ 50kg, body mass index (BMI) within the range of 19 ~ 28 kg/m2 (including 19 and 28) (BMI= weight (kg)/height 2 (m2));
3. Subjects have no childbirth plans and agree to take effective contraceptive measures within 3 months of the last medication;
4. The subject can communicate well with the researcher, understand and comply with the requirements of the study, understand and sign the informed consent.

Exclusion Criteria:

1. History of or currently suffering from any serious clinical diseases such as diseases in circulatory system, endocrine system, nervous system, digestive system, respiratory system, genitourinary system, hematology, immunology, psychiatry, and metabolic abnormalities, or any other diseases may interfere with the test results;
2. Any surgery within 6 months before screening, or plan to perform surgery during the study period, or who have previously undergone any surgery that affects gastrointestinal absorption (including gastrectomy, bowel resection, gastric reduction surgery, etc.)
3. Blood donation or massive blood loss (≥200 mL), or received blood transfusion, or used blood products within 3 months before screening;
4. History of allergy to drugs, food or other substances;
5. Frequent use of sedatives, sleeping pills or other addictive drugs; History of drug abuse within 1 year prior to screening; Positive for urine drug abuse screening test;
6. Participated in any clinical trial and took the study drug within 3 months prior to the first administration;
7. Used any prescription drug or herbal tonic within 1 month before the first administration; Have used any over-the-counter (OTC) medicines, food supplements (including vitamins, calcium tablets, etc.) within 2 weeks prior to the first administration;
8. Those who had smoked more than 5 cigarettes per day in the previous 3 months before screening and could not stop using any tobacco products during the study period; Nicotinic test positive;
9. Frequent drinkers in the previous 6 months before screening, i.e., those who drink more than 14 units of alcohol per week (1 unit = 285 mL beer, or 25 mL spirits, or 100 mL wine) and cannot stop using any alcoholic products during the study period; alcohol test positive;
10. Abnormal vital signs, physical examination, 12-lead ECG, abdominal B-ultrasound, chest radiograph, routine blood test, biochemical test, routine urine test and blood coagulation test with clinical significance;
11. Hepatitis B surface antigen positive, hepatitis C antibody positive, syphilis antibody positive, HIV antibody positive;
12. Subjects have taken and do not agree to stop using any drink or food containing methylxanthine, such as coffee, tea, cola, chocolate, etc. from 48 hours before the first administration until end of the study;, subjects have taken and do not agree to discontinue any beverage or food containing grapefruit from 7 days prior to initial administration until end of the study; Those who have special requirements on diet and cannot follow a uniform diet;
13. Subjects who are considered to have other factors that are not appropriate to participate in this study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; single dose of Famitinib on Day 1, and co-administered with Rifampicin on Day 16	Drug: Famitinib capsule; single dose and co-administrated with Rifampicin capsule; Other Names: SHR1020; Drug: Rifampicin capsule; repeated doses of Rifampicin capsule; Other Names: Rifampicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Famitinib	Pharmacokinetics parameters of Famitinib	Day 1 to Day 24
AUC0-t of Famitinib	Pharmacokinetics parameters of Famitinib	Day 1 to Day 24
AUCinf of Famitinib	Pharmacokinetics parameters of Famitinib	Day 1 to Day 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax of Famitinib	Pharmacokinetics parameters of Famitinib	Day 1 to Day 24
T1/2 of Famitinib	Pharmacokinetics parameters of Famitinib	Day 1 to Day 24
CL/F of Famitinib	Pharmacokinetics parameters of Famitinib	Day 1 to Day 24
Vz/F of Famitinib	Pharmacokinetics parameters of Famitinib	Day 1 to Day 24
incidence of adverse events/serious adverse events	safety evaluation based on NCI-CTC AE 5.0	from ICF signing date to approximate Day 31

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• Li T, Li X, Jiang X, Wang C, Sun F, Liu Y, Lin P, Shi P, Fu Y, Gao X, Zhang Y, Cao Y. The effect of rifampin on the pharmacokinetics of famitinib in healthy subjects. Cancer Chemother Pharmacol. 2022 Nov;90(5):409-415. doi: 10.1007/s00280-022-04474-8. Epub 2022 Sep 15.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2020
• Primary Completion (Actual): August 13, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: July 28, 2020
• First Posted (Actual): July 31, 2020

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 27, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin
• Other Study ID Numbers: FMTN-I-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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