Surufatinib DDI With a PPI and a CYP3A Inducer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1 |
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 Design
Arms and Interventions
| 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:
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| 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:
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Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria
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Non-smoking, healthy male or female between the ages of 18 and 55 years (inclusive)
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Body mass index (BMI) > 18 and ≤ 29 kg/m2
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Females must be of non-childbearing potential or surgically sterile
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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
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Evidence of clinically significant cardiovascular, hepatic, GI, renal, respiratory, endocrine, hematological, neurological, or psychiatric disease or abnormalities
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Known history of any GI surgery or any condition possibly affecting drug absorption, however appendectomy and hernia repair will be allowed
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Clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to first dose
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Known food allergy deemed clinically significant.
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Clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations
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Systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg
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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
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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.
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History of smoking or use of nicotine-containing substances within the previous 2 months
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History of drug or alcohol misuse in the previous 6 months
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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)
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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
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Consumes grapefruit, starfruit, Seville oranges, or their products within 7 days before first dose
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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
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Weight loss or gain of > 10% within 4 weeks before first dose
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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
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Uses any over-the-counter (OTC) medications or prescription drugs within 2 weeks before first dose
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Uses CYP3A inducers (including St. John's wort) or inhibitors within 2 weeks before first dose
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Allergic to the study drugs (including rabeprazole or rifampin) or to any of the excipients
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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)
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Female participant is pregnant, lactating, or breastfeeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | West Coast Clinical Trials (WCCT) | Cypress | California | United States | 90630 |
Sponsors and Collaborators
- Hutchison Medipharma Limited
Investigators
- Principal Investigator: Youngiun Kim, MD, WCCT Global Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2020-012-00US1