Surufatinib DDI With a PPI and a CYP3A Inducer

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04510649
• Other study ID #: 2020-012-00US1
• Status: Completed
• Phase: Phase 1
• Start date: July 9, 2020
• Est. completion date: March 2, 2021

Study information

• Verified date: August 2020
• Source: Hutchison Medipharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: March 2, 2021
• Est. primary completion date: September 11, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

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
• 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

Locations

Country	Name	City	State
United States	West Coast Clinical Trials (WCCT)	Cypress	California

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Cmax of Surufatinib	Pharmacokinetics of Surufatinib by assessment of maximum plasma Surufatinib concentration	up to 16 days
Secondary	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