Food Effect Study of Single Dose of Fruquintinib (HMPL-013) in Healthy Subjects

Study Overview
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Brief Summary
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This study will determine the effect of food on the pharmacokinetics (PK) of a single dose of 4mg fruquintinib in normal healthy subjects.

Detailed Description
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This study will be an open-label, randomized, two-period, crossover PK food effect study of fruquintinib administered orally at 4mg. Subjects will be screened for eligibility up to 14 days prior to entry into the study. For each of 2 study periods, 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 each of the 2 study periods, subjects will receive a single oral dose of 4 mg fruquintinib in either the fasted or fed state. Subjects will remain at the CRU for at least 120 hours after administration of study drug for collection of serial blood samples for pharmacokinetic (PK) analysis and safety monitoring. Subjects will return to the CRU for safety assessment for up to 336 hours postdose.

Official Title
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A Single Center, Open-label, Randomized, Two-period Crossover Food Effect Study of Single Doses of Fruquintinib (HMPL-013) in Healthy Subjects

Conditions
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Food Effect of Fruquintinib in Health Subjects

Intervention / Treatment
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* Drug: fruquintinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males , between 18 and 45 years of age, inclusive. Body mass index (BMI) within the range of 19 to 25 kg/m2, inclusive. In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, and vital signs. Adequate hepatic, renal, heart, and hematologic functions Male subjects who are either sterile or agree to use, during the period from informed consent until 90 days following Study Completion, 1 of the following approved methods of contraception: a double barrier method (eg, male condom with spermicide, use by female sexual partner of an intrauterine device with spermicide, a female condom with spermicide, contraceptive sponge with spermicide, a diaphragm with spermicide, or use of a cervical cap with spermicide); a sterile sexual partner; a female sexual partner using an intravaginal system (eg,NuvaRing®); or a partner using an oral, implantable, transdermal, or injectable contraceptives. Able to comprehend and willing to sign an informed consent form (ICF). Exclusion Criteria: Significant history or clinical manifestation of any significant metabolic/endocrine, allergic, dermatological, hepatic, renal, hematological, pulmonary, immune, cardiovascular, gastrointestinal, genitourinary, neurological, or psychiatric disorder(as determined by the Investigator). History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator. History of stomach or intestinal surgery, nephrectomy, cholecystectomy or resection that would potentially alter absorption and/or excretion of orally administered drugs as determined by the investigator (appendectomy and/or hernia repair may be allowed). History or presence of an abnormal ECG, which, in the Investigator's opinion, is clinically significant. Diagnosis of alcoholism or drug addiction within 1 year prior to Period 1 Check-in. Participation in any other investigational drug study in which receipt of an investigational study drug occurred within 5 half-lives or 30 days, whichever is longer prior to informed consent. Use of any prescription medications or products within 14 days prior to Period 1 prior to informed consent. Use of any over-the-counter (OTC), non-prescription preparations (including vitamins, minerals, and phytotherapeutic, herbal, dietary supplements, or plant derived preparations) within 7 days prior to each study period Check-in. Use of alcohol-, grapefruit-, Seville orange-, or caffeine-containing foods, juices, or beverages within 72 hours prior to each study period Check-in. Use of known hepatic or renal clearance altering agents (eg, erythromycin, cimetidine, barbiturates, phenothiazines, or herbal/plant derived preparations such as St. John's Wort, etc.) for a period of 60 days prior to informed consent; Poor peripheral venous access. Donation of blood ≥ 250 mL from 30 days prior to informed consent until study completion, inclusive, or of plasma from 2 weeks prior to informed consent until study completion, inclusive. Receipt of blood products within 2 months prior to Period 1 Check-in; Blood pressure greater than 140/90 mmHg confirmed by repeat at Screening or at Period 1 Check-in. Any acute or chronic condition that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in this clinical study.

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: A-fasted dosing followed by fed dosing<br>Experimental: Fasted dosing of fruquintinib followed by fed dosing; Dosing in the fasted state followed by fed dosing | Drug: fruquintinib<br>* Fruquintinib 4 mg capsule, 2 discrete single doses separated by 2-weeks<br>* Other names: HMPL-013;|
| Experimental: B-fed dosing followed by fasted dosing<br>Experimental: Fed dosing of fruquintinib followed by fasted dosing; Dosing in the fed state followed by fasted dosing | Drug: fruquintinib<br>* Fruquintinib 4 mg capsule, 2 discrete single doses separated by 2-weeks<br>* Other names: HMPL-013;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • To determine the effect of food on the PK of a single dose of 4mg fruquintinib in normal healthy subjects. | Blood samples for PK analysis of serum fruquintinib levels will be collected for a 2-week period following each of 2 doses. | Planned Enrollment/Screening Duration: Approximately 2 weeks. Length of Each Confinement: Approximately 7days prior to dose until approximately 120 hours postdose. Planned Study Conduct Duration: Approximately 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • To assess the safety and tolerability of single doses of 4mg fruquintinib | Safety will be assessed by physical exam, clinical laboratory evaluations and ECGs. | Planned Enrollment/Screening Duration: Approximately 2 weeks. Length of Each Confinement: Approximately 7days prior to dose until approximately 120 hours postdose. Planned Study Conduct Duration: Approximately 6 weeks |