Fruquintinib Hepatic Impairment Study

NCT05216367 | Completed Phase 1 FDA Drug

• 1 other identifier: 2021-013-00US1
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

An Open-label, Phase 1 Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Fruquintinib

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (3)

• AUC 0-t

  Area under the plasma concentration-time curve from time 0 to time of the last measurable concentration

  Day 1 to Day 11

• AUC 0-inf

  Area under the plasma concentration-time curve from time 0 to infinity (if data permit)

  Day 1 to Day 11

• Maximum Plasma Concentration [Cmax]

  To determine the maximum observed plasma concentration of Fruquintinib

  Day 1 to Day 11

Secondary Outcomes (1)

• Incidence of Adverse Events/Serious Adverse Events

  Day 1 to Day 11

Study Arms (3)

Cohort 1 (healthy subjects)

EXPERIMENTAL

8 healthy subjects with normal hepatic function will receive a single dose of 5 mg (1x5 mg) fruquintinib

Drug: Fruquintinib

Cohort 2 (moderate hepatic impairment)

EXPERIMENTAL

8 subjects with moderate hepatic impairment will receive a single dose of 2 mg (2 x 1 mg) fruquintinib

Drug: Fruquintinib

Cohort 3 (mild hepatic impairment)

EXPERIMENTAL

8 subjects with mild hepatic impairment will receive a single dose of 5 mg (1 x 5 mg) fruquintinib

Drug: Fruquintinib

Interventions

Fruquintinib DRUG

Fruquintinib will be administered as a single oral dose on the morning of day 1 under fasting conditions

Also known as: HMPL-013

Cohort 1 (healthy subjects); Cohort 2 (moderate hepatic impairment); Cohort 3 (mild hepatic impairment)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Subjects
• Male or female between the ages of 18 and 75 years old (inclusive)
• BMI \>18 and ≤40 kg/m2 and body weight not \<50 kg at screening.
• 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 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 treatment phase, 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.
• 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 clinical condition within the last 30 days before screening
• The subject must have a condition consistent with hepatic impairment and associated symptoms but otherwise be determined to be in good health in the opinion of the Investigator.
• Subjects with ascites must not have a paracentesis within 3 months of screening.
• If diabetic, the subject must have the diabetes controlled (as determined by the Investigator).
• Concomitant medications to treat underlying disease states or medical conditions related to hepatic impairment are allowed. Subjects must be on a stable dose of medication and/or treatment regimen for at least 2 weeks before dosing as well as during the study.
• Subjects with Normal Hepatic Function
• The subject must be without hepatic disease and have normal hepatic function

You may not qualify if:

• 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 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 clinically significant renal laboratory findings, including estimated creatinine clearance \<60 mL/min as calculated by the Cockcroft-Gault equation.
• The subject has participated in a clinical study of another drug before screening, 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
• The subject has consumed grapefruit, starfruit, Seville oranges, or their products within 7 days prior to day 1.
• 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 day 1.
• The subject has received blood or blood products within 8 weeks, or donated blood or blood products within 8 weeks prior to day 1 or donated double red cells within 16 weeks prior to day 1.
• The subject has experienced a weight loss or gain of \>10% within 4 weeks prior to day 1 as documented by recent medical history and weight at screening to check-in (excluding subjects with moderate hepatic impairment).
• The subject has used any drug that is a strong inhibitor or inducer of CYP3A within 2 weeks (within 3 weeks for St. John's wort) prior to day 1 or will require use during the treatment period.
• The subject is allergic to the study drug or to any of its excipients.
• Female subject who is pregnant or planning to become pregnant, lactating, or breastfeeding.

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (2)

Clinical Pharmacology of Miami

Miami, Florida, 33014-3616, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Interventions

HMPL-013

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2022
• First Posted: January 31, 2022
• Study Start: March 11, 2022
• Primary Completion: October 25, 2022
• Study Completion: October 25, 2022
• Last Updated: October 31, 2022

Record last verified: 2022-10

Locations

US (2)