Fruquintinib Food Effect and Proton Pump Inhibitor Study

NCT04645940 | Completed Phase 1 FDA Drug

• 1 other identifier: 2020-013-00US1
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this is to evaluate the effect of food and the effect of a proton pump inhibitor (rabeprazole) on the pharmacokinetics of fruquintinib.

Conditions

Drug Interaction; Food-drug Interaction

Outcome Measures

Primary Outcomes (3)

• AUC(0-t) of fruquintinib: area under the plasma-concentration time curve from time 0 to time of the last measurable concentration

  Pharmacokinetics of fruquintinib by assessment of area under the plasma concentration time curve from zero to the last measurable concentration

  Up to 36 days

• AUC(0-inf) of fruquintinib

  Pharmacokinetics of fruquintinib by assessment of area under the plasma concentration curve from zero extrapolated to infinity (if data permit)

  up to 36 days

• Cmax of fruquintinib

  Pharmacokinetics of fruquintinib by assessment of maximum plasma fruquintinib concentration

  up to 36 days

Secondary Outcomes (1)

• Number of participants with treatment emergent adverse events as assessed by CTCAE v5.0

  up to 36 days

Study Arms (2)

Fed/Fasted

EXPERIMENTAL

fruquintinib 5 mg with food on Day 1 and fruquintinib 5 mg without food on Day 15. 40 mg rabeprazole from Day 23 to Day 29. On Day 29, fruquintinib 5 mg one hour after rabeprazole dose.

Drug: fruquintinib with food/fruquintinib without food/fruquintinib with rabeprazole

Fasted/Fed

EXPERIMENTAL

fruquintinib 5 mg without food on Day 1 and fruquintinib 5 mg with food on Day 15. 40 mg rabeprazole from Day 23 to Day 29. On Day 29, fruquintinib 5 mg one hour after rabeprazole dose.

Drug: fruquintinib without food/fruquintinib with food/fruquintinib with rabeprazole

Interventions

fruquintinib with food/fruquintinib without food/fruquintinib with rabeprazole DRUG

fruquintinib 5 mg with food on Day 1 and fruquintinib 5 mg without food on Day 15. 40 mg rabeprazole from Day 23 to Day 28. 40 mg rabeprazole one hour before 5 mg fruquintinib Day 29.

Also known as: HMPL-013, rabeprazole 40 mg

Fed/Fasted

fruquintinib without food/fruquintinib with food/fruquintinib with rabeprazole DRUG

fruquintinib 5 mg without food on Day 1 and fruquintinib 5 mg with food on Day 15. 40 mg rabeprazole from Day 23 to Day 28. 40 mg rabeprazole one hour before 5 mg fruquintinib Day 29.

Also known as: HMPL-013, rabeprazole 40 mg

Fasted/Fed

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoking, healthy male or female between the ages of 18 and 55 years (inclusive) at the time of informed consent.
• Body mass index (BMI) \> 18 and ≤ 29 kg/m2 at Screening.
• Females must be of non-childbearing potential (eg, postmenopausal \[defined as cessation of all menstrual periods for at least 1 year confirmed by follicle-stimulating hormone (FSH) test ≥ 40 UI/L\] or surgically sterile by total hysterectomy, bilateral oophorectomy, or bilateral tubal ligation).
• 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.

You may not qualify if:

• Evidence of clinically significant cardiovascular, hepatic, gastrointestinal (GI), renal, respiratory, endocrine, hematological, neurological, or psychiatric disease or abnormalities.
• History of any GI surgery or any condition possibly affecting drug absorption (eg, cholecystectomy, gastrectomy, achlorhydria, peptic ulcer disease, history of stomach or intestinal surgery or resection, except appendectomy and hernia repair will be allowed).
• Clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to the first dose.
• Food allergy deemed clinically significant per PI.
• Clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations at Screening or Day -1 Check-in (baseline).
• Systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg at Screening or Day -1 Check-in (baseline).
• Clinically significant ECG abnormality, including a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTcF interval \> 480 msec), or has a family history of prolonged QTc syndrome or sudden death.
• 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, as determined by medical history or subject's verbal report and confirmed by cotinine test at Screening and Check-In for any one of the treatment periods.
• History of drug or alcohol misuse within 6 months prior to Screening or a positive urine drug test at Screening or Check-in for any one of the treatment periods.
• 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 study of other 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, whichever is longer, or the subject is currently enrolled in another clinical study.
• Consumed grapefruit, starfruit, Seville oranges, or their products within 7 days prior to the first dose.
• 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.
• Weight loss or gain of \> 10% within 4 weeks prior to the first dose.

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

WCCT

Cypress, California, 90630, United States

Location

MeSH Terms

Interventions

HMPL-013; Rabeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Youngiun Kim, MD

  WCCT Global Inc

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: November 27, 2020
• Study Start: September 24, 2020
• Primary Completion: November 18, 2020
• Study Completion: November 18, 2020
• Last Updated: June 18, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)