Catequentinib Hydrochloride (AL3818) Drug-Drug Interaction Study in Healthy Volunteers

Official title

A Non-Randomized, Open-Label Clinical Study of Catequentinib Hydrochloride (AL3818) Drug-Drug Interaction (DDI) With Itraconazole and Ticagrelor in Healthy Volunteer Subjects

Overview

This is a non-randomized, open-label, fixed-sequence drug-drug interaction study to evaluate the effects of itraconazole and ticagrelor on the pharmacokinetics of catequentinib hydrochloride (AL3818) in healthy volunteers.

Detailed description

This is a non-randomized, open-label, single-center, fixed-sequence drug-drug interaction (DDI) study to evaluate the effects of itraconazole and ticagrelor on the pharmacokinetics of catequentinib hydrochloride (AL3818) in healthy adult subjects. Eligible subjects will receive a single dose of AL3818 alone and in combination with multiple doses of itraconazole or ticagrelor in different periods. Serial blood samples will be collected to determine plasma concentrations of AL3818. Safety and tolerability will be monitored throughout the study.

Interventions

• Drug AL3818 Capsule
  dosage form: capsule; strength: 8 mg; orally in fasted condition
• Drug Itraconazole capsule
  dosage form: capsule; strength: 0.1 g. Oral
• Drug Ticagrelor Tablets
  dosage form: tablet; strength: 90 mg.Oral

Primary outcome measures

• PK parameters of AL3818 include [Time frame: through study completion, an average of 1 year]
• PK parameters of AL3818 include [Time frame: through study completion, an average of 1 year]
• PK parameters of AL3818 include [Time frame: through study completion, an average of 1 year]
• PK parameters of AL3818 include [Time frame: through study completion, an average of 1 year]
• PK parameters of AL3818 include [Time frame: through study completion, an average of 1 year]
• PK parameters of AL3818 include [Time frame: through study completion, an average of 1 year]
• PK parameters of AL3818 include [Time frame: through study completion, an average of 1 year]
• PK parameters of AL3818 include [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

A subject is eligible for enrollment in the study only if all of the following criteria are met:

• Male or female; aged between 18 and 45 years old (inclusive).
• Male subjects weight ≥50 kg, female subjects weight ≥45 kg, body mass index (BMI) between 19.0 and 26.0 kg/m2 , BMI= weight (kg)/height2 (m2 ) (inclusive).
• Physical examination, vital signs, 12-lead electrocardiogram (ECG), laboratory tests (blood routine, urine routine, blood biochemistry, blood lipid, coagulation function and thyroid function, etc.) and chest X-ray at screening showed no clinically significant abnormalities, and the clinical study doctor judged them qualified.
• The subject voluntarily signed a written informed consent form and is able to communicate well with the investigator.

Exclusion criteria

Subjects who meet any of the following criteria before screening will be excluded from the study:

• History of severe systemic diseases (including cardiovascular, digestive, urinary, respiratory, endocrine, immune, blood and lymphatic, skeletal/muscular, nervous and other system diseases), history of liver and kidney insufficiency, history of mental diseases, history of drug dependence, bleeding tendency (such as recent trauma, recent surgery, coagulation dysfunction, active or recent gastrointestinal bleeding), history of active pathological bleeding, history of intracranial hemorrhage, family history of hypertension;
• History of dysphagia or any gastrointestinal diseases affecting drug absorption, digestive system diseases (such as peptic ulcer, pancreatitis, colitis, etc.) within 3 months;
• Allergic to any component of the investigational product (AL3818, itraconazole capsule, ticagrelor tablet) and its excipients, with a history of drug or food allergy, or history of specific allergy (asthma, urticaria, eczema, etc.);
• Subjects who have had clinically significant major diseases or major surgical procedures within 3 months prior to;
• Subjects who donated blood within 3 months, or planned to donate blood within the study period, or Subjects who had blood transfusion or blood loss ≥200 mL within 4 weeks;
• Participation in any clinical trial as a subject within 3 months;
• Subjects with drug abuse history within 5 years or drug use within 3 months or positive urine drug abuse screening at baseline;
• Anyone who has taken any prescription, over-the-counter, vitamin or herbal medicine within 2 weeks or 5 half-lives (whichever is longer);
• Any drug known to be an inhibitor or inducer of CYP3A4 enzymes or a sensitive substrate (Appendix 4), any drug known to be a P-gp inhibitor or substrate (Appendix 5), any drug known to be a BCRP inhibitor or substrate (Appendix 6), or any drug known to cause a risk of torsades de pointes (TdP) (Appendix 7) within 4 weeks;
• Vaccination within 3 months or planned during this trial;
• Subjects with a history of bleeding and needle phobia, unable to tolerate intravenous indwelling needle injection;
• Subjects with neurological/psychiatric, respiratory, cardiovascular, digestive tract, blood and lymphatic system, endocrine, musculoskeletal disorders, liver and kidney dysfunction, or any other diseases and physiological conditions that may affect the study results at screening;
• Screening or baseline 12-lead ECG with QTcF interval ≥ 450 ms (males), QTcF interval ≥ 460 ms (females); or ECG abnormal and considered abnormal and clinically significant by the investigator;
• Laboratory test results during screening period or baseline period meet the following abnormal range requirements and are considered abnormal and clinically significant by the investigator:

• Abnormal liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST)≥ULN;
• Abnormal coagulation function: activated partial thromboplastin time (APTT) or international normalized ratio (INR) ≥ULN;
• Abnormal thyroid function: Free triiodothyronine (FT3) or free thyroxine (FT4) or thyroid stimulating hormone (TSH) higher than ULN;
• Subjects with hepatitis B surface antigen quantitative determination positive, hepatitis C antibody quantitative determination positive, human immunodeficiency virus antigen antibody determination positive or treponema pallidum antibody determination positive at screening period or baseline period;
• Have special requirements for diet and fail to comply with the diet and corresponding regulations provided by the clinical trial institution;
• Those who cannot control special diet (including pitaya, mango, grapefruit and/or xanthine diet, caffeine-containing food or beverage, etc.) during the trial;
• Strenuous exercise within 48 hours prior to the first dose, or planned strenuous exercise during the trial;
• Regular drinkers within 6 months or during the trial, i.e. drinking more than 21 units of alcohol (male) or 14 units of alcohol (female) per week (1 unit =360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine), or unable to stop drinking during the trial, or positive alcohol breath test at baseline;
• Smoking more than 5 cigarettes per day in the 3 months, or using any tobacco products during the trial;
• Pregnant or lactating women or those with positive blood pregnancy test results;
• Subjects who have used long-acting estrogen or progesterone injection or implant tablets within 6 months or during the trial;
• Women of childbearing age who have had unprotected sex with their partners within 14 days prior to screening;
• Male or female subjects of childbearing potential do not agree to use an effective method of contraception from the time of signing informed consent until 6 months after the last dose (see Section 10.3 for details of specific methods of contraception);
• Sperm or egg donation or fertility planning within 6 months from signing the informed consent form to the last dose;
• Vulnerable subjects such as the investigator himself/herself, relevant personnel of the study site and their family members, students and subordinates of the investigator, and employees of the sponsor;
• Any other conditions that, in the opinion of the investigator, make the subject unsuitable for participation in this clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing GoBroad Hospital Ethics Review Committee — Beijing

Identifiers

NCT: NCT07438886 · AL3818-US-004-DDI-HV

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗