Fruquintinib DDI Study With P-gp and BCRP Substrates

NCT05368805 | Completed Phase 1 FDA Drug

• 1 other identifier: 2021-013-00US3
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Fruquintinib DDI Study with P-gp and BCRP Substrates

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• PK parameter for dabigatran and rosuvastatin: AUC0-t:

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

  Day 1 to Day 13

• PK parameter for dabigatran and rosuvastatin: AUC0-inf:

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

  Day 1 to Day 13

• PK parameter for dabigatran and rosuvastatin: Cmax:

  maximum observed plasma concentration

  Day 1 to Day 13

Secondary Outcomes (4)

• Incidence of AEs/SAEs

  Day 1 to Day 13

• PK parameter of fruquintinib and metabolite M11: AUC0-t:

  Day 1 Day 13

• PK parameters of fruquintinib and metabolite M11: AUC0-inf:

  Day 1 to Day 13

• PK parameters of fruquintinib and metabolite M11: Cmax:

  Day 1 to Day 13

Study Arms (2)

Part A

EXPERIMENTAL

On Day 1, a single oral dose of dabigatran etexilate 150 mg will be given under fasted conditions and serial PK samples will be collected as indicated on the schedule of events. On Day 5, subjects will receive a single oral dose of fruquintinib 5 mg at approximately 1 hour prior to administration of a single oral dose of dabigatran etexilate 150 mg under fasted conditions and serial PK samples will be collected

Drug: Fruquintinib; Drug: Dabigatran Etexilate

Part B

EXPERIMENTAL

On Day 1, a single oral dose of rosuvastatin 10 mg will be given under fasted conditions and serial PK samples will be collected as indicated on the schedule of events. On Day 5, subjects will receive a single oral dose of rosuvastatin 10 mg with fruquintinib 5 mg under fasted conditions and serial PK samples will be collected

Drug: Fruquintinib; Drug: Rosuvastatin

Interventions

Fruquintinib DRUG

Fruquintinib will be administered as a single oral 5mg dose on the morning of day 5

Also known as: HMPL-013

Part A; Part B

Dabigatran Etexilate DRUG

Dabigatran Etexilate will be administered as a single oral dose 150mg on the morning of day 1 and morning of day 5

Part A

Rosuvastatin DRUG

Rosuvastatin will be administered as a single oral dose 10mg on the morning of day 1 and the morning of day 5

Part B

Eligibility Criteria

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

You may qualify if:

• The subject is male or female between the ages of 18 and 55 years old (inclusive) at the time of informed consent.
• The subject has a body mass index (BMI) \>18 and ≤29 kg/m2 at screening.
• Female subjects must be of non-childbearing potential (eg, postmenopausal \[defined as cessation of all menstrual periods for at least 1 year without an alternative medical cause, and confirmed by follicle-stimulating hormone (FSH) test ≥40 IU/L\] or surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation).
• Male subjects with partners of childbearing potential must always use a condom and must agree in addition to use a highly effective form(s) of contraception, that results in a low failure rate (\<1% per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire study period, and for 90 days after taking the last dose of study drug. Such methods include:
• Oral hormonal contraception (combined estrogen/progestogen, or progestogen-only) associated with inhibition of ovulation
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal ligation
• Vasectomy
• True sexual abstinence in line with the preferred and usual lifestyle of the subject.
• Highly effective contraception should always be combined with an additional barrier method (eg, diaphragm, with a spermicide).
• The subject must provide written informed consent prior to any study-specific screening procedures.
• The subject is willing and able to comply with all aspects of the protocol, as determined by the Investigator.

You may not qualify if:

• Clinical laboratory test results from the coagulation panel (international normalized ratio \[INR\], prothrombin time, and activated partial thromboplastin time) must be within the normal laboratory reference ranges or deemed not clinically significant by the Investigator and Sponsor.
• The subject has clinically significant renal laboratory findings, including estimated glomerular filtration rate \<80 mL/min as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• The subject has a known history of any gastrointestinal surgery or any condition possibly affecting drug absorption (eg, cholecystectomy, gastrectomy, achlorhydria, peptic ulcer disease, history of stomach or intestinal surgery or resection). Appendectomy and hernia repair are allowed.
• The subject had a clinically significant illness within 8 weeks or a clinically significant infection within 4 weeks prior to the first dose.
• The subject has evidence of a clinically significant deviation from normal in the physical examination, vital signs, or clinical laboratory determinations at screening or at Day -1 check-in (baseline).
• The subject has systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg.
• The subject has a 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.
• The subject has a 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 check in for each treatment period.
• The subject has a history of drug or alcohol misuse within 6 months prior to screening or a positive urine drug test at screening or at check in for each treatment period.
• The subject has been 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).
• The subject has participated in a clinical trial 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 trial.
• 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 experienced a weight loss or gain of \>10% within 4 weeks prior to the first dose as noted by medical history and weight at screening and check-in.
• The subject has received blood or blood products within 4 weeks, or donated blood or blood products within 8 weeks prior to the first dose or donated double red cell within 16 weeks prior to first dose.

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (1)

PPD Development

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; Dabigatran; Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines

Study Design

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

Study Record Dates

• First Submitted: April 21, 2022
• First Posted: May 10, 2022
• Study Start: March 2, 2022
• Primary Completion: April 22, 2022
• Study Completion: April 22, 2022
• Last Updated: October 6, 2022

Record last verified: 2022-10

Locations

US (1)