Drug-drug Interaction Study Between Fluconazole and Famitinib in Healthy Subjects

A Single-center, Open-label, Fixed-sequence Study to Evaluate the Effects of Fluconazole on the Pharmacokinetics and Safety of Famitinib in Healthy Subjects

An open-label, fixed-sequence, drug-drug interaction study to evaluate the effects of fluconazole on the pharmacokinetics and safety of famitinib in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Tumor
• Intervention / Treatment: Drug: Fluconazole、Famitinib

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. With my consent and informed consent, I am willing and able to complete the study in accordance with the requirements of the experimental protocol;
2. Healthy male or female aged 18-45 years (including threshold) on the date of signing the informed consent form;
3. Male body weight ≥ 50 kg, female body weight ≥ 45 kg, body mass index (BMI) in the range of 19.0-26.0 kg / m2 (including the critical value);
4. Physical examination, vital signs, laboratory measurements (blood routine, blood biochemistry, urine routine test, coagulation function, etc.), 12-lead ECG, abdominal B-ultrasound, chest X-ray, etc. are normal or abnormal, but the researcher has no clinical significance according to NCI CTCAE 5.0 standard;
5. Fertile subjects had no family planning and had to take acceptable contraceptive measures and no plans to donate eggs and sperm within 3 months from the date of signing informed consent to the last medication; the serum pregnancy test of fertile women within 24 hours before the first administration of the study drug should be negative.

Exclusion Criteria:

1. Those who have previously suffered from primary diseases of important organs, including but not limited to neuropsychiatric, cardiovascular, digestive tract, respiratory system, urinary, endocrine, blood, immune and other diseases, which are judged by the researchers to be unsuitable for the trial;
2. Subjects who have received any previous operation affecting gastrointestinal absorption;
3. Subjects who had received any surgery within 6 months before screening, or planned to undergo surgery during the study period;
4. Those who lost blood or donated more than 400 ml or received blood transfusion within 3 months before screening;
5. HBsAg positive, HCVAb positive, HIV antibody positive, syphilis antibody positive;
6. History of drug use in the past 5 years or drug abuse, or drug screening positive;
7. Smoking and alcohol addict and unable to stop smoking during the test period; those with positive alcohol screening; those with positive nicotine screening;
8. Subjects who have swallowing resistance or obstacle that will affect the drug absorption;
9. Allergic constitution, including severe drug allergy or drug allergy history; known allergy to fluconazole and famitinib or its excipients;
10. Those who have participated in other clinical trials and taken the study drug within 3 months before taking the study drug for the first time;
11. Inducers or inhibitors of CYP3A4 were taken within 4 weeks before the first administration of study drug;
12. Taking any prescription drug, over-the-counter drug, traditional Chinese medicine or food supplement within 2 weeks before taking the study drug for the first time;
13. Ingestion of grapefruit containing products, fruit juice, food or beverage containing methylxanthine or alcohol within 48 hours before taking the study drug for the first time; taking strenuous exercise; or having other factors affecting the absorption, distribution, metabolism and excretion of drugs;
14. Lactating women;
15. The researchers considered that the subjects had any other factors that were not suitable for the trial.

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: Fluconazole and Famitinib interaction	Drug: Fluconazole、Famitinib; Fluconazole, once daily on Days 12 to 24; Famitinib, once daily on Days 1 and 15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed serum concentration (Cmax) for famitinib	Day 1 to Day 25
Area under the concentration-time curve from time zero to time t (AUC0-t,) for famitinib	Day 1 to Day 25
Area under the concentration-time curve extrapolated to infinity (AUC0-∞.) for famitinib (if applicable)	Day 1 to Day 25

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to maximum observed serum concentration (Tmax) for famitinib	Day 1 to Day 25
Time to elimination half-life (t1/2) for famitinib	Day 1 to Day 25
Apparent oral clearance (CL/F) for famitinib	Day 1 to Day 25
Apparent Volume of Distribution (Vz/F) for famitinib	Day 1 to Day 25
Tmax for famitinib metabolite SHR116637	Day 1 to Day 25
Cmax for famitinib metabolite SHR116637	Day 1 to Day 25
AUC0-t, for famitinib metabolite SHR116637	Day 1 to Day 25
AUC0-∞. for famitinib metabolite SHR116637(if applicable)	Day 1 to Day 25
t1/2 for famitinib metabolite SHR116637	Day 1 to Day 25
The incidence and severity of adverse events/serious adverse events (based on NCI-CTC AE 5.0)	Day 1 to Day 25

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2022
• Primary Completion (Actual): May 2, 2022
• Study Completion (Actual): May 2, 2022

Study Registration Dates

• First Submitted: December 6, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: FMTN-I-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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