A Bioequivalence Study of Famitinib Malate on Healthy Chinese Volunteers

Study Overview
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Brief Summary
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The primary objective is to evaluate the bioequivalence of famitinib malate capsules in new and old formulations after oral dose under fasted condition on healthy Chinese subjects. The secondary objective is to evaluate the safety after famitinib malate capsules oral dose on healthy Chinese subjects.

Official Title
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A Single-centre, Single-dose, Randomized, Open-label and Two-cycle Crossover Bioequivalence Study of Famitinib Malate Capsules in Old and New Formulation on Healthy Chinese Subjects

Conditions
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Healthy Adult Subjects

Intervention / Treatment
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* Drug: Famitinib malate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects aged 18 45 (including 18 and 45 years old); Body weight ≥ 50kg, body mass index (BMI) within the range of 19   26kg/m2 (including 19 and 26 kg/m2) (BMI= weight (kg)/height 2 (m2)); Consent to abstinence or take effective non-drug contraception measures during the study and for at least 3 months after the last drug administration. The subjects were able to communicate well with the researchers, understand and comply with the requirements of this study, understand and sign the informed consent; Exclusion Criteria: Anyone who has suffered from any clinical serious disease such as the circulatory system, endocrine system, nervous system, digestive system, respiratory system, urogenital system, hematology, immunology, psychiatry and metabolic abnormalities, or any other disease which can affect the study results. Those who have undergone surgery within 6 months before the trial, or plan to perform surgery during the study period; Those who donated blood or suffered heavy blood loss (≥200 mL), received blood transfusions, or used blood products within 3 months before enrollment; Have a history of allergies to drugs, food or other substances; Have taken sedatives, sleeping pills or other addictive medicines within 1 year before the study; Those with positive results in urine drug abuse screening; Those who have participated in any clinical trials and have taken study drugs within 3 months before the first administration; Those who have taken any medicine within 4 weeks before the first administration (including prescription medicines, non-prescription medicines, Chinese herbal medicines, vitamins, calcium tablets and other food supplements); Those who smoked more than 5 cigarettes per day within 3 months before the study and who could not stop using any tobacco products during the study; Regular drinkers within 6 months before the test, that is, drinking more than 14 units of alcohol per week (1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine), and any alcohol-containing products cannot be stopped during the study Those who are positive for alcohol breath test; Those with any abnormal result (clinically significant) of vital signs, physical examination, 12-lead electrocardiogram, chest radiograph, abdominal ultrasound, colour Doppler echocardiography, hematology, clinical chemistry, urinalysis and coagulation; Hepatitis B virus surface antigen is positive, or hepatitis C virus antibody is positive, or treponema pallidum antibody is positive, or human immunodeficiency virus antibody is positive; The subject refuses to stop any beverage or food containing methylxanthine, such as coffee, tea, cola, chocolate, etc., within 48 hours before the first dose until the end of the study; The subject refuses to stop any beverage or food containing grapefruit; Those who have special dietary requirements and cannot accept the unified diet; Other factors of the subject that are not suitable for participating in the study judged by the investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Treatment group TR Intervention: Drug: famitinib malate, new formulation; Intervention: Drug: famitinib malate, old formulation. Treatment group RT Intervention: Drug: famitinib malate, old formulation; Intervention: Drug: famitinib malate, new formulation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group TR<br>Intervention: Drug: famitinib malate, new formulation; Intervention: Drug: famitinib malate, old formulation. | Drug: Famitinib malate<br>* TR group: The first period，the subjects will be administrated with Famitinib malate in new formulation, then conduct blood collection within 192h; 14 days washout；The second period，the subjects will be administrated with Famitinib malate in old formulation, then conduct blood collection within 192h. RT group: The first period，the subjects will be administrated with Famitinib malate in old formulation, then conduct blood collection within 192h; 14 days washout；The second period，the subjects will be administrated with Famitinib malate in new formulation, then conduct blood collection within 192h.<br>|
| Experimental: Treatment group RT<br>Intervention: Drug: famitinib malate, old formulation; Intervention: Drug: famitinib malate, new formulation. | Drug: Famitinib malate<br>* TR group: The first period，the subjects will be administrated with Famitinib malate in new formulation, then conduct blood collection within 192h; 14 days washout；The second period，the subjects will be administrated with Famitinib malate in old formulation, then conduct blood collection within 192h. RT group: The first period，the subjects will be administrated with Famitinib malate in old formulation, then conduct blood collection within 192h; 14 days washout；The second period，the subjects will be administrated with Famitinib malate in new formulation, then conduct blood collection within 192h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameter: Cmax | Peak plasma concentration （Cmax） | through study completion, an average of 30 days | 
| Pharmacokinetics parameter: AUC | Area under the plasma concentration versus time curve（AUC） | through study completion, an average of 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameter: Tmax | Time of maximum observed concentration (Tmax) | through study completion, an average of 30 days | 
| Pharmacokinetics parameter: t1/2 | Half time (t1/2) | through study completion, an average of 30 days | 
| Pharmacokinetics parameter: λz | First order elimination rate constant (λz) | through study completion, an average of 30 days | 
| The number of participants with treatment-related adverse events assessed by CTCAE V5.0 | An adverse event is any untoward medical occurrence in the subjects or clinical study participants. | through study completion, an average of 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Old formulation, New formulation