A Bioequivalence Study of Sunitinib Malate Capsules.

Study Overview
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Brief Summary
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A randomized, open, two-period, two-sequence crossover trial design used to assess the pharmacokinetics and safety of Sunitinib Malate Capsules in healthy volunteers under fed condition, and compare the bioequivalence of Sunitinib Malate Capsules produced by Pfizer and Chia Tai Tianqing Pharmaceutical Group Co., Ltd, respectively.

Official Title
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A Bioequivalence Study of Sunitinib Malate Capsules in Healthy Volunteers Under Fed Condition.

Conditions
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Gastrointestinal Stromal Tumors, Renal Cell Carcinoma, Pancreatic Neuroendocrine Tumor

Intervention / Treatment
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* Drug: Sunitinib malate capsules generic product
* Drug: Sunitinib malate capsules reference product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The informed consent was signed before the study, fully understood the content and process of the study and the potential adverse reactions. Ability to complete the study in accordance with the protocol requirements. Chinese healthy adults aged 18-45 (included), male. Weight not less than 50 kg with a body mass index (BMI) between 18 and 28 kg/m2 (included, BMI = weight /height2). Health status: No mental abnormalities, no medical history of cardiovascular system, nervous system, respiratory system, digestive system, urinary system, endocrine system and metabolic abnormalities. Vital signs, physical examination, laboratory examination, electrocardiogram and imaging examinations should be normal or abnormal with no clinical significance. Volunteers (including the partner) should ensure proper contraception from 2 weeks before dosing to at least 6 months after the last study drug administration, and ensure that one or more contraception measures are used in sexual during this period. Exclusion Criteria: Previously suffered from neuropsychiatric system, respiratory system, cardiovascular system, gastrointestinal system, hemolymphatic system, liver and kidney insufficiency, endocrine system, musculoskeletal system diseases or other diseases, and the investigator judges that the past medical history may affect drug metabolism or safety. History of dysphagia or any gastrointestinal disorder affecting drug absorption. Have a history of intracranial hemorrhage or any disease that increases the risk of bleeding (such as repeated rhinorrhea, purpura, hemorrhoids, acute gastritis, etc.). Male subjects with clinically significant abnormal ECG history, or corrected QT (QTC) interval greater than 450 ms. People who have a history of dizziness of needles or blood. People who are allergic to sunitinib malate and its metabolites or its excipients. People who smoked more than 5 cigarettes per day in the 3 months before the clinical trial. People who have a history of drug and/or alcohol abuse (drinking 14 units of alcohol per week: 1 unit = 360 mL of beer or 45 mL of 40% spirits or 150 mL of wine). Blood donation or massive blood loss (> 450mL) within 2 months before taking study drug. Taking any drugs and contraceptives that change the activity of liver enzymes within 28 days before the study drug administration (such as liver drug enzyme inhibitors chlorpromazine, cimetidine, ciprofloxacin, metronidazole, etc.; liver drug enzyme inducers barbiturates, carbamazepine, rifampicin, dexamethasone, etc.). Taking any prescription drug, over-the-counter drug, any vitamin product, or herbal remedies within 14 days prior to the study drug administration. Need to use tobacco, alcohol and caffeinated drinks during the clinical trial, or certain foods that may affect metabolism (including dragon fruit, mango, grapefruit, and/or xanthine diet, etc.), or have significant changes in diet or exercise habits before the clinical trial , or other factors that affect drug absorption, distribution, metabolism, excretion, etc. Taking any study drug or participated in another drug clinical trial within 2 months before the study drug administration. Abnormal vital sign examination results with clinically significance. Abnormal clinical laboratory tests with clinically significance. Abnormal chest x-ray with clinically significance. Screening positive for hepatitis (including hepatitis B and C), Acquired immunodeficiency syndrome (AIDS), and syphilis. People who were positive in drug screening or had a history of drug abuse in the past five years or used drugs in the 3 months before the clinical trial. Difficulty or intolerance to blood collection by venipuncture. Acute illness occurred during the pre-study screening phase or prior to study medication. People who are unable to comply with ward management regulations. People who are unable to complete the clinical trial due to personal reasons. Other conditions that the investigator judges are not suitable for inclusion.

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib malate capsules generic product<br>Single dose of Sunitinib malate capsule under fed condition on Day 1 and Day 29, respectively. | Drug: Sunitinib malate capsules generic product<br>* Sunitinib is an inhibitor targeting multiple receptor tyrosine kinases (RTK).<br>|
| Active Comparator: Sunitinib malate capsules reference product<br>Single dose of Sunitinib malate capsule under fed condition on Day 1 and Day 29, respectively. | Drug: Sunitinib malate capsules reference product<br>* Sunitinib is an inhibitor targeting multiple receptor tyrosine kinases (RTK).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | Maximum plasma concentration | Before administration and 2, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72, 96, 120, 168 hours after administration. | 
| Time to maximum concentration (Tmax) | Time to reach maximum concentration after drug administration | Before administration and 2, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72, 96, 120, 168 hours after administration. | 
| Area under the drug-time curve (AUC) | Area under the drug-time curve | Before administration and 2, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72, 96, 120, 168 hours after administration. | 
| Apparent terminal elimination half-life (t1/2) | Apparent terminal elimination half-life (t1/2) | Before administration and 2, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72, 96, 120, 168 hours after administration. | 
| Apparent volume of distribution (Vd/F) | Apparent volume of distribution | Before administration and 2, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72, 96, 120, 168 hours after administration. | 
| Clearance rate (CL/F) | Clearance rate | Before administration and 2, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72, 96, 120, 168 hours after administration. | 
| Apparent terminal elimination rate constant (λz) | Apparent terminal elimination rate constant | Before administration and 2, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72, 96, 120, 168 hours after administration. | 
| Relative bioavailability (F) | Relative bioavailability (F) of the tested product to reference product | Before administration and 2, 4, 6, 8, 10, 12, 14, 16, 24, 48, 72, 96, 120, 168 hours after administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AE) | Incidence of adverse events (AE) evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) V5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Severity of adverse events (AE) | Severity of adverse events (AE) evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal blood biochemistry results | The proportion of subjects with abnormal blood biochemistry results evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal blood routine | The proportion of subjects with abnormal blood routine results evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal urinalysis results | The proportion of subjects with abnormal urinalysis results evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal coagulation function | The proportion of subjects with abnormal coagulation function evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal thyroid function | The proportion of subjects with abnormal thyroid function evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal blood pressure | The proportion of subjects with abnormal blood pressure evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal pulse | The proportion of subjects with abnormal pulse evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal body temperature | The proportion of subjects with abnormal body temperature evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. | 
| Proportion of subjects with abnormal 12-lead electrocardiogram (ECG) | The proportion of subjects with abnormal 12-lead ECG evaluated in accordance with the National Cancer Institute's Common Toxicity Criteria (NCI CTC) v5.0. | From the date of randomization until the date of withdrawal from the study for any reason. Assessed up to 40 days. |