A Food Effect Phase I Study of the Volitinib in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate to determine the effect of food on the PK of a single dose of 600 mg Volitinib and its two major metabolites in healthy subjects.

Detailed Description
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The purpose of this study is to evaluate to determine the effect of food on the PK( pharmacokinetics) of a single dose of 600 mg Volitinib and its two major metabolites in healthy subjects and to assess the safety and tolerability of single doses of 600mg in healthy subjects.This study will be an open-label, randomized, four-period, crossover PK food effect study of Volitinib administered orally at 600 mg. Subjects will be screened for eligibility up to 14 days prior to entry into the study,there will be 4 treatments,2 weeks follow-up.

Official Title
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A Single Center, Open-label, Randomized, Four-Sequence, Four-period Crossover Study to Investigate Food Effect on the Pharmacokinetics of Single Dose of Volitinib in Healthy Subjects

Conditions
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Food Effect, Health Subjects

Intervention / Treatment
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* Drug: Volitinib


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: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Volitinib ,after high fat meal intake<br>A:single oral Volitinib after high fat meal intake | Drug: Volitinib<br>* 600mg Volitinib ,single dose,oral<br>* Other names: HMPL-504;|
| Experimental: Volitinib,after general diet<br>B:single oral Volitinib, after general diet | Drug: Volitinib<br>* 600mg Volitinib ,single dose,oral<br>* Other names: HMPL-504;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics | The following PK parameters will be derived from the plasma concentration-time profile of Volitinib following administration:Area Under Curve (AUC), both from time zero to time with last observation and from time zero to infinity;;Maximum plasma concentration (Cmax);Time to reach the Cmax (Tmax);Apparent oral Clearance (CL/F);Apparent oral Volume of distribution (Vz/F);Other parameters, such as elimination half-life | 1-3days after every drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | AE(adverse event) will be summarized by type and severity | 1 day to the 14days after every drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food Effect, Health subjects