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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Part A; Drug: Part B

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).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • West Coast Clinical Trials (WCCT)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surufatinib and Rabeprazole (Part A); Part A: Surufatinib 300 mg on study days 1 and 11 Rabeprazole 40 mg on study days 5 - 11	Drug: Part 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; Other Names: Rabeprazole 30 mg
Experimental: Surufatinib and Rifampin (Part B); Part B: Surufatinib 300 mg on study days 1 and 12 Rifampin 600 mg on study days 5-15	Drug: Part 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; Other Names: Rifampin 600 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Pharmacokinetics of surufatinib by assessment of area under the plasma concentration time curve from zero to the last measurable concentration	up to 16 days
AUC of Surufatinib	Pharmacokinetics of surufatinib by assessment of area under the plasma concentration curve from zero extrapolated to infinity (if data permit)	up to 16 days
Cmax of Surufatinib	Pharmacokinetics of Surufatinib by assessment of maximum plasma Surufatinib concentration	up to 16 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment emergent adverse events as assessed by CTCAE v5.0	To evaluate the safety, in healthy subjects, of a single dose of 300 mg surufatinib administered alone and with rabeprazole or rifampin	up to 16 days

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Investigators: Principal Investigator: Youngiun Kim, MD, WCCT Global Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2020
• Primary Completion (Actual): September 11, 2020
• Study Completion (Actual): March 2, 2021

Study Registration Dates

• First Submitted: August 10, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rabeprazole; Rifampin
• Other Study ID Numbers: 2020-012-00US1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No