A Mass Balance Study to Investigate the Absorption, Metabolism, and Excretion Of [14C] Fruquintinib
A Mass Balance Study to Investigate the Absorption, Metabolism, and Excretion Of [14C] Fruquintinib
This will be an open-label, single-center study to evaluate pharmacokinetics and safety of
 HMPL-013 in approximately 6 healthy male subjects receiving a single oral 5mg dose of
 HMPL-013 containing approximately 100 microcuries of [14C] HMPL-013. This study will
 investigate the absorption, drug biotransformation and mass balance of HMPL-013, seek to
 identify the compound's major metabolites and supply information for clinical application.
This study will be an open-label, mass balance study of fruquintinib administered orally at
 5mg (100mCi). Subjects will be screened for eligibility up to 14 days prior to entry into the
 study. For study period, subjects will be admitted to the clinical research unit (CRU) on the
 day before dosing and fast overnight (approximately 10 hours). On the morning of dosing for
 study period, subjects will receive a single oral dose of 5 mg fruquintinib in the fasted
 state. Subjects will remain at the CRU for at least 336 hours after administration of study
 drug for collection of serial blood samples for pharmacokinetic (PK) analysis and safety
 monitoring.
Inclusion Criteria:

 1. A Healthy Male Volunteer between 18 and 40 years of age inclusive;

 2. A Body Mass Index (BMI) within the range of 19 to 25 kg/m2 and a total body weight
 >50kg;

 3. Medically normal subjects with no significant abnormal findings at the screening vital
 signs, physical examination, electrocardiogram (ECG), and laboratory parameters as
 evaluated by the investigator;

 4. Fertile male subjects and their partners are willing to undergo contraception as
 follows: condom, contraceptive sponge, contraceptive gel, contraceptive diaphragm,
 intrauterine devices, hormonal contraceptives (oral or injectable), subepidermal
 contraceptive implant and other contraception methods during the study and until 1
 year after taking the dose of investigational product,

 5. Subject must voluntarily consent to participate in this study, provide their written
 informed consent prior to start of any study- specific procedures and be willing to
 comply with all study procedures.

 Exclusion Criteria:

 1. Subjects who have a family history of coronary heart disease;

 2. Subjects who have a known history of bleeding such as gingival hemorrhage, epistaxis
 and hemorrhoid bleeding etc.;

 3. Subjects have hypertension (Systolic Pressure ≥140 mmHg or Diastolic Pressure ≥90
 mmHg);

 4. Subjects who are taking, or have taken any drugs that affect metabolism or
 prescription medication during the screening or within 30 days prior to the screening;
 Subjects who are taking, or have taken any OTC, herbal remedies or Vitamin during the
 screening or within 14 days prior to the screening; Subjects who are taking, or have
 taken any plant extracts like Hypericum Perforatum L. which are not therapeutic but
 have health function and can affect the absorption and metabolism during the screening
 or within 3 days prior to the screening; Subjects who have participated in another
 clinical trial within 2 months prior to the screening;

 5. Subjects who are taking, or have taken any drugs which have toxicity to major organs
 during the screening or within 3 months prior to the screening;

 6. Subjects who test positive for nicotine screening or can't quit smoking completely in
 the study;

 7. Subjects who have history or presence of any clinically significant diseases within 3
 months prior to the screening;

 8. Subjects who have history or presence of gastrointestinal, hepatic, renal diseases or
 any other known condition that can affect the absorption, distribution, metabolism or
 excretion of the investigational product;

 9. Subjects who have chronic constipation, diarrhea, irritable bowel syndrome or
 inflammatory bowel disease;

 10. Subjects who have hemorrhoids or perianal complications with regular hematochezia;

 11. Subjects who have a known history of severe allergic reaction such as drug allergy or
 had an acute allergic rhinitis or food allergy within 14 days prior to the study
 medication;

 12. Subjects who have donated blood or plasma more than 500ml within 2 months prior to the
 study medication or more than 50ml within 14 days prior to the study medication;

 13. Subjects who have had a positive test for hepatitis B (HBsAg) or hepatitis C (excluded
 immunization);

 14. Subjects who have had a positive test for human immunodeficiency virus (HIV);

 15. Subjects who have taken vaccination during the screening or within 6 months prior to
 the screening;

 16. Subjects who have any prior history of substance abuse or treatment (including
 alcohol) ;

 17. Subjects who can't understand the purpose, extent and possible outcomes of the study
 because of mental disease;

 18. Adult subjects who are imprisoned or whose freedom are restricted because of
 administrative problem or legal issues;

 19. Subjects who can't comply with the protocol such as discontinue the follow-up and
 finish the study according to the protocol;

 20. Subjects who are involved in the study design and proceeding such as investigator,
 pharmacist, clinical research coordinator or other related personnel;

 21. Subjects who have any other unsuitable or adverse condition to be determined by the
 investigator;

 22. Subjects who have participated in a radiolabeled clinical trial prior to study
 medication;

 23. Subjects who have been exposed to significant radiation (e.g., x-ray investigation, CT
 investigation, more than one time radiation exposure in barium meal examination) or
 whose occupation requires exposure to radiation in the last 12 months.