Phase I Clinical Trial in Healthy Male Volunteers

Exclusion Criteria

• •Subjects are excluded from participation in the study if any of the following criteria apply:
• •Subjects with, or a history of, cancer, diabetes or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, hematological, dermatological, venereal, neurological, psychiatric or other major disorder;
• •Presence or history of GI, hepatic or renal disease or any other condition (including surgery) known to interfere with the absorption, distribution, metabolism or excretion of medicines; Hutchison MediPharma Ltd. Clinical Study Protocol HMPL-004-1002 Confidential \& Proprietary 27 Final 20 July 2011
• •Systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 40 to 90 mmHg, and/or pulse rate outside the range of 40 to 100 bpm after one repeat at screening or check-in;
• •Abnormal ECGs at screening
• •History of clinically significant drug and/or food allergies as determined by the Principal Investigator (PI);
• •Subjects will be excluded if they experience arrhythmia of any clinical significance;
• •Subject is not willing to abstain from alcohol for 48 hours prior to the start of the first dose until completion of the post-study follow-up assessments;
• •Any history (within 2 years) or current diagnosed alcoholism defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (One unit is equivalent to a half-pint of beer or 1 measure of spirits or 1 glass of wine.);
• •Recent history or current diagnosed drug abuse;
• •Tobacco or nicotine use within the 6 months prior to first dose until the follow-up assessment, or a positive urine screen for cotinine;
• •Hypersensitivity or idiosyncratic reaction to compounds related to the study drug;
• •Use of substances known to be strong inhibitors or inducers of cytochrome P450 enzymes (eg, macrolides, calcium channel blockers, ritonavir, rifampin, St. John's Wort, etc.) within 30 days prior to the first dose;
• •Use of prescription or non-prescription drugs, including high-dose vitamins, herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication (except for strong inhibitors or inducers of cytochrome P450 enzymes);
• •Consumption of food or beverage containing grapefruit or cranberry within 7 days prior to the dose of study medication;
• •Recent significant changes in body weight due to dieting or nutritional treatment;
• •Donation of whole blood in excess of 500 mL within 56 days prior to checkin;
• •Plasma donation within 7 days prior to check-in;
• •Subject participated in an investigational clinical study within 30 days prior to the first dosing, or days calculated as ten times the half-life of the compound which the subject was treated with, whichever is longer. Factors other than the half-life of the compound, such as accumulation of tissue, muscle or organ, should also be considered for the enrollment;
• •Exposure to 4 or more investigational products within 12 months prior to the first dosing day; Hutchison MediPharma Ltd. Clinical Study Protocol HMPL-004-1002 Confidential \& Proprietary 28 Final 20 July 2011
• •Positive screen for HIV, hepatitis B, and/or hepatitis C at screening;
• •Positive urine screen for drugs of abuse at screening or check-in; and
• •Any condition that, in the opinion of the Principal Investigator, would complicate or compromise the study, or the well-being of the subject 4.2.3 General and Dietary Restrictions
• •The following items are not to be consumed for 48 hours (2 days) prior to the first dose until the last scheduled blood sample collection of the study:
• •Caffeine/xanthine such as coffee, tea, chocolate, and all caffeine containing soft drinks or energy drinks;
• •Alcoholic beverages and/or other alcohol containing products; and
• •Any foods containing poppy seeds.
• •The following items are not to be consumed for 14 days prior to the first dose and throughout the study until the last scheduled blood sample collection:
• •Grapefruit, pomelo, cranberry, or grapefruit, pomelo, or cranberry-containing products. While in the CPU, subjects will not be allowed additional sugar in beverages or on cereal, though limited use of other sweeteners is allowed.