Healthy
Conditions
Brief summary
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.
Detailed description
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).
Interventions
DRUGPart A
in Part A, all subjects will receive Surufatinib 300 mg in a single dose on study days 1 and 11 and receive Rabeprazole 30 mg single dose on study days 5 through 11
DRUGPart B
in Part B, all subjects will receive Surufatinib 300 mg in a single dose on study days 1 and 12 and receive Rifampin 600 mg single dose on study days 5 through 16
Sponsors
Hutchison Medipharma Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC (0-t) of Surufatinib [ Time Frame: Up to Day 15 ] Pharmacokinetics of surufatinib by assessment of area under the plasma concentration time curve from zero to the last measurable concentration | up to 16 days | Pharmacokinetics of surufatinib by assessment of area under the plasma concentration time curve from zero to the last measurable concentration |
| AUC of Surufatinib | up to 16 days | Pharmacokinetics of surufatinib by assessment of area under the plasma concentration curve from zero extrapolated to infinity (if data permit) |
| Cmax of Surufatinib | up to 16 days | Pharmacokinetics of Surufatinib by assessment of maximum plasma Surufatinib concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment emergent adverse events as assessed by CTCAE v5.0 | up to 16 days | To evaluate the safety, in healthy subjects, of a single dose of 300 mg surufatinib administered alone and with rabeprazole or rifampin |
Countries
United States
Outcome results
None listed