Surufatinib DDI With a PPI and a CYP3A Inducer

Ph. 1, Open-label, 2 Part, 2 Period Fixed-Sequence Crossover Study to Assess the Effect of Rabeprazole, a Proton Pump Inhibitor, and the Effect of Rifampin, a Strong CYP3A Inducer, on the Pharmacokinetics of Surufatinib in Healthy Subjects

The purpose of this is to evaluate the effect of proton pump inhibitor (rabeprazole) and the effect of a CYP3A inducer (rifampin) on the pharmacokinetics of Surufatinib.

This study will be a single center, open-label, 2 part, 2 period fixed-sequence crossover study to be conducted with 28 healthy male and female subjects (part A and part B). Subjects will be enrolled in either part A or part B.

In Part A, subjects will be administered surufatinib alone in treatment Period 1 and co-administered with rabeprazole in treatment Period 2.

In Part B, subjects will be administered surufatinib alone in treatment Period 1 and co-administered with rifampin in treatment Period 2.

PK samples will be collected through out both study periods.Subjects will be confined in the clinic from check-in on Day -1 through the end-of study visit on Day 15 (part A) and Day 16 (part B).

Inclusion Criteria

• Non-smoking, healthy male or female between the ages of 18 and 55 years (inclusive)
• Body mass index (BMI) > 18 and ≤ 29 kg/m2
• Females must be of non-childbearing potential or surgically sterile
• Males who have not had a successful vasectomy and are partners of women of childbearing potential must use, or their partners must use, a medically acceptable method of contraception starting for at least 1 menstrual cycle prior to and throughout the entire study period, and for 2 weeks after the last dose of study drug. Those with partners using hormonal contraceptives must also use an additional approved method of contraception such as a condom with spermicide. Males who have had a successful vasectomy (confirmed azoospermia, documentation needed) require no additional contraception. No sperm donation is allowed during the study period and for 90 days after study drug discontinuation.

Exclusion Criteria

• Evidence of clinically significant cardiovascular, hepatic, GI, renal, respiratory, endocrine, hematological, neurological, or psychiatric disease or abnormalities
• Known history of any GI surgery or any condition possibly affecting drug absorption, however appendectomy and hernia repair will be allowed
• Clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to first dose
• Known food allergy deemed clinically significant.
• Clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations
• Systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg
• Clinically significant ECG abnormality, including a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTcF interval > 480 msec), or had a family history of prolonged QTc syndrome or sudden death
• Has Gilbert's syndrome as indicated by total bilirubin > upper limit of normal (ULN) and subsequent measurement of direct bilirubin is not within normal range.
• History of smoking or use of nicotine-containing substances within the previous 2 months
• History of drug or alcohol misuse in the previous 6 months
• Diagnosed with acquired immune deficiency syndrome (AIDS) or has performed tests that are positive for human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV)
• Participated in a clinical trial of other drug and the last use of other study drug is less than 5 times the half-life or 4 weeks, whichever is longer, or the subject is currently enrolled in another clinical trial
• Consumes grapefruit, starfruit, Seville oranges, or their products within 7 days before first dose
• Consumes herbal preparations/medications, including, but not limited to kava, ephedra (ma huang), Ginkgo biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng within 7 days before first dose
• Weight loss or gain of > 10% within 4 weeks before first dose
• Received blood or blood products within 4 weeks, or donated blood or blood products within 8 weeks, or donated double red blood cells within 16 weeks before first dose
• Uses any over-the-counter (OTC) medications or prescription drugs within 2 weeks before first dose
• Uses CYP3A inducers (including St. John's wort) or inhibitors within 2 weeks before first dose
• Allergic to the study drugs (including rabeprazole or rifampin) or to any of the excipients
• Cannot abstain from using a proton pump inhibitor (PPI) or a histamine H2 receptor antagonist (H2 blocker) or locally acting antacids (eg, Gaviscon, Gelusil, Maalox, Milk of Magnesia, Mylanta, Rolaids, Tums)
• Female participant is pregnant, lactating, or breastfeeding