Surufatinib DDI With a PPI and a CYP3A Inducer

HUTCHMED

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Part B

Drug: Part A

Study type

Interventional

Funder types

Industry

Identifiers

NCT04510649

2020-012-00US1

Details and patient eligibility

About

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.

Full 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).

Enrollment

28 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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