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Surufatinib Hepatic Impairment Study

Primary Purpose

Hepatic Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Surufatinib
Surufatinib
Sponsored by
Hutchison Medipharma Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Hepatic Impairment

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

All Subjects

  • Male or female between 18 and 75 (inclusive)
  • Subject has BMI >18 and ≤40 kg/m^2 and body weight not ≤50 kg at screening.
  • The subject is a non-smoker or light smoker who smokes no more than 10 cigarettes, 2 cigars, 2 pipes, or other nicotine equivalents (eg, vape, snuff, gum) of tobacco per day; willing to limit smoking during the treatment period to 4 cigarettes or 1 cigar per day.
  • Females 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.

Subjects with Hepatic Impairment

  • For moderate hepatic impairment, the subject must have a Child-Pugh score of 7 to 9. For mild hepatic impairment, the subject must have a Child-Pugh score of 5 to 6.
  • The subject must have no clinically significant change in disease status within the last 30 days before screening.
  • If diabetic, the subject must have the disease controlled
  • Subjects with ascites must not have a paracentesis within 3 months of screening.
  • The subject must have blood pressure between 90 and 160 mm Hg systolic, inclusive, and not higher than 100 mm Hg diastolic.

Subjects with Normal Hepatic Function

  • The subject must be without hepatic disease and have normal hepatic function
  • The subject must be in good health
  • The subject must have blood pressure between 95 and 150 mm Hg systolic, inclusive, and no higher than 90 mm Hg diastolic

Exclusion Criteria:

All Subjects

  • The subject has evidence of clinically significant cardiovascular, GI, renal, respiratory, endocrine, hematological, neurological, or psychiatric disease or abnormalities.
  • The subject has a known history of any GI surgery or any condition possibly affecting drug absorption.
  • The subject has a clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to the first dose.
  • The subject has a clinically significant ECG abnormality
  • The subject has been diagnosed with acquired immune deficiency syndrome (AIDS), or tests positive for human immunodeficiency virus (HIV).
  • The subject has participated in a clinical study of another drug before dosing, and the time since the last use of other study drug is less than 5 times the half-life or 4 weeks before Day 1, whichever is longer, or is currently enrolled in another clinical study.
  • The subject has consumed grapefruit, starfruit, Seville oranges, or their products within 7 days prior to the first dose.
  • The subject has consumed herbal preparations/medications, including, but not limited to, kava, ephedra (ma huang), Ginkgo biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng, within 7 days prior to the first dose.
  • The subject has received blood or blood products within 8 weeks, or donated blood or blood products within 8 weeks prior to the first dose, or donated double red cells within 16 weeks prior to the first dose.
  • The subject has used any drug that is a strong inhibitor or inducer (including St. John's wort) of CYP3A or P-gp within 2 weeks prior to first dose or will require use during study treatment period.
  • The subject is allergic to the study drug or to any of its excipients.
  • Female subjects who are pregnant or planning to become pregnant, lactating, or breastfeeding.
  • The subject has used a proton pump inhibitor (PPI) within 4 days prior to the first dose or a histamine 2 (H2) receptor antagonist (H2 blocker) within 2 days prior to the first dose.

Subjects with Hepatic Impairment

  • The subject has clinically significant vital sign abnormalities at screening or baseline.
  • The subject has used acetaminophen at doses >1 g/day within 2 weeks prior to study drug administration.
  • The subject has a history or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study
  • The subject has Gilbert's syndrome, liver transplant, Wilson's disease, autoimmune liver disease
  • The subject has previously been diagnosed with hepatocellular carcinoma.
  • The subject has acute or exacerbating hepatitis, fluctuating or rapidly deteriorating hepatic function
  • The subject has a history of drug misuse within 6 months prior to screening or a positive drug test at screening or on Day -1.
  • The subject has evidence of current or recent abuse of alcohol
  • The subject has received therapy known to exacerbate hepatic impairment within 4 weeks of study drug administration.
  • The subject is taking antiviral therapy for treatment of active hepatitis infection at the time of screening.

Subjects with Normal Hepatic Function

  • The subject has evidence of clinically significant hepatic illness or abnormalities.
  • The subject has evidence of a clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations at screening or baseline.
  • The subject tests positive for Hepatitis B virus (HBV), HBsAg, Hepatitis C virus (HCV), or Hepatitis C antibody
  • The subject has used any prescription or nonprescription drugs, including over-the-counter (OTC) medications or vitamins, within 2 weeks prior to the first dose, unless otherwise specified.
  • The subject has a history of drug or alcohol misuse within 6 months prior to screening or a positive drug test at screening or on Day -1.

Sites / Locations

  • Orange County Research Center
  • Orlando Clinical Research Center, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3 (if enrolled)

Arm Description

Subjects with Normal Hepatic Function: All patients to receive study drug (Surufatinib 250mg) on Day 1

Subjects with Moderate Hepatic Impairment: All patients to receive study drug (Surufatnib 250mg) on Day 1

Subjects with Mild Hepatic Impairment: All patients to receive study drug (Surufatnib 250mg) on Day 1

Outcomes

Primary Outcome Measures

AUC0-t
Area under the plasma concentration-time curve from time 0 to time of the last measurable concentration
AUC0-inf
Area under the plasma concentration-time curve from time 0 to infinity (if data permit)
Cmax
Maximum observed plasma concentration

Secondary Outcome Measures

Number of participants with treatment emergent adverse events as assessed by NCI CTCAE v5.0
To evaluate the safety of a single dose of 250mg surufatinib administered in subjects with mild (if enrolled) and moderate hepatic impairment

Full Information

First Posted
February 4, 2021
Last Updated
August 29, 2022
Sponsor
Hutchison Medipharma Limited
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1. Study Identification

Unique Protocol Identification Number
NCT04755075
Brief Title
Surufatinib Hepatic Impairment Study
Official Title
A Phase 1 Study To Assess The Effect Of Hepatic Impairment On The Pharmacokinetics Of Surufatinib
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
February 12, 2021 (Actual)
Primary Completion Date
October 11, 2021 (Actual)
Study Completion Date
October 11, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hutchison Medipharma Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
An open-label, multicenter, single-dose, single-period, sequential study to determine the effect of hepatic impairment on the PK of surufatinib.
Detailed Description
This is a phase 1, open-label, multicenter, single-dose, single-period, sequential study with the primary objective of determining the effect of moderate and mild hepatic impairment on the PK of surufatinib. The secondary objective is to evaluate the safety in subjects with moderate and mild (if enrolled) hepatic impairment and subjects with normal hepatic function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Subjects with Normal Hepatic Function: All patients to receive study drug (Surufatinib 250mg) on Day 1
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Subjects with Moderate Hepatic Impairment: All patients to receive study drug (Surufatnib 250mg) on Day 1
Arm Title
Cohort 3 (if enrolled)
Arm Type
Experimental
Arm Description
Subjects with Mild Hepatic Impairment: All patients to receive study drug (Surufatnib 250mg) on Day 1
Intervention Type
Drug
Intervention Name(s)
Surufatinib
Other Intervention Name(s)
HMPL-012
Intervention Description
Subjects to receive Surufatinib 250 mg on Day 1
Intervention Type
Drug
Intervention Name(s)
Surufatinib
Other Intervention Name(s)
HMPL-012
Intervention Description
Subjects to receive Surufatinib 250 mg on Day 1
Primary Outcome Measure Information:
Title
AUC0-t
Description
Area under the plasma concentration-time curve from time 0 to time of the last measurable concentration
Time Frame
From Day 1 to Day 7
Title
AUC0-inf
Description
Area under the plasma concentration-time curve from time 0 to infinity (if data permit)
Time Frame
From Day 1 to Day 7
Title
Cmax
Description
Maximum observed plasma concentration
Time Frame
From Day 1 to Day 7
Secondary Outcome Measure Information:
Title
Number of participants with treatment emergent adverse events as assessed by NCI CTCAE v5.0
Description
To evaluate the safety of a single dose of 250mg surufatinib administered in subjects with mild (if enrolled) and moderate hepatic impairment
Time Frame
From Day 1 to Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: All Subjects Male or female between 18 and 75 (inclusive) Subject has BMI >18 and ≤40 kg/m^2 and body weight not ≤50 kg at screening. The subject is a non-smoker or light smoker who smokes no more than 10 cigarettes, 2 cigars, 2 pipes, or other nicotine equivalents (eg, vape, snuff, gum) of tobacco per day; willing to limit smoking during the treatment period to 4 cigarettes or 1 cigar per day. Females 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. Subjects with Hepatic Impairment For moderate hepatic impairment, the subject must have a Child-Pugh score of 7 to 9. For mild hepatic impairment, the subject must have a Child-Pugh score of 5 to 6. The subject must have no clinically significant change in disease status within the last 30 days before screening. If diabetic, the subject must have the disease controlled Subjects with ascites must not have a paracentesis within 3 months of screening. The subject must have blood pressure between 90 and 160 mm Hg systolic, inclusive, and not higher than 100 mm Hg diastolic. Subjects with Normal Hepatic Function The subject must be without hepatic disease and have normal hepatic function The subject must be in good health The subject must have blood pressure between 95 and 150 mm Hg systolic, inclusive, and no higher than 90 mm Hg diastolic Exclusion Criteria: All Subjects The subject has evidence of clinically significant cardiovascular, GI, renal, respiratory, endocrine, hematological, neurological, or psychiatric disease or abnormalities. The subject has a known history of any GI surgery or any condition possibly affecting drug absorption. The subject has a clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to the first dose. The subject has a clinically significant ECG abnormality The subject has been diagnosed with acquired immune deficiency syndrome (AIDS), or tests positive for human immunodeficiency virus (HIV). The subject has participated in a clinical study of another drug before dosing, and the time since the last use of other study drug is less than 5 times the half-life or 4 weeks before Day 1, whichever is longer, or is currently enrolled in another clinical study. The subject has consumed grapefruit, starfruit, Seville oranges, or their products within 7 days prior to the first dose. The subject has consumed herbal preparations/medications, including, but not limited to, kava, ephedra (ma huang), Ginkgo biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng, within 7 days prior to the first dose. The subject has received blood or blood products within 8 weeks, or donated blood or blood products within 8 weeks prior to the first dose, or donated double red cells within 16 weeks prior to the first dose. The subject has used any drug that is a strong inhibitor or inducer (including St. John's wort) of CYP3A or P-gp within 2 weeks prior to first dose or will require use during study treatment period. The subject is allergic to the study drug or to any of its excipients. Female subjects who are pregnant or planning to become pregnant, lactating, or breastfeeding. The subject has used a proton pump inhibitor (PPI) within 4 days prior to the first dose or a histamine 2 (H2) receptor antagonist (H2 blocker) within 2 days prior to the first dose. Subjects with Hepatic Impairment The subject has clinically significant vital sign abnormalities at screening or baseline. The subject has used acetaminophen at doses >1 g/day within 2 weeks prior to study drug administration. The subject has a history or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study The subject has Gilbert's syndrome, liver transplant, Wilson's disease, autoimmune liver disease The subject has previously been diagnosed with hepatocellular carcinoma. The subject has acute or exacerbating hepatitis, fluctuating or rapidly deteriorating hepatic function The subject has a history of drug misuse within 6 months prior to screening or a positive drug test at screening or on Day -1. The subject has evidence of current or recent abuse of alcohol The subject has received therapy known to exacerbate hepatic impairment within 4 weeks of study drug administration. The subject is taking antiviral therapy for treatment of active hepatitis infection at the time of screening. Subjects with Normal Hepatic Function The subject has evidence of clinically significant hepatic illness or abnormalities. The subject has evidence of a clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations at screening or baseline. The subject tests positive for Hepatitis B virus (HBV), HBsAg, Hepatitis C virus (HCV), or Hepatitis C antibody The subject has used any prescription or nonprescription drugs, including over-the-counter (OTC) medications or vitamins, within 2 weeks prior to the first dose, unless otherwise specified. The subject has a history of drug or alcohol misuse within 6 months prior to screening or a positive drug test at screening or on Day -1.
Facility Information:
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
Orlando Clinical Research Center, Inc.
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States

12. IPD Sharing Statement

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Surufatinib Hepatic Impairment Study

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