A Phase I Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of HS-10506 in Healthy Chinese Adult Participants

Обзор

A single-center, open-label, fixed-sequence, self-controlled phase I clinical trial aimed at evaluating the effect of itraconazole capsules(CYP3A inhibitor) on the pharmacokinetics of HS-10506 tablets in healthy participants.

Подробное описание

On Day 1 and Day 11 of the trial, HS-10506 tablets will be orally administered under fasting conditions in the morning. From Day 7 to Day 15, itraconazole capsules (0.2 g, administered as two 0.1 g capsules) will be taken orally once daily for nine consecutive days. On the morning of Day 11, itraconazole capsules and HS-10506 tablets will be taken concurrently. When administered alone or in combination with itraconazole capsules, HS-10506 tablets will be given under fasting conditions. When administered alone, itraconazole capsules will be taken within 15 minutes after a meal, with approximately 240 mL of water.

Вмешательства

• Препарат HS-10506, Itraconazole
  HS-10506: Administered under fasting conditions in the morning. Itraconazole: Itraconazole capsules (0.2 g) are taken orally once daily for nine consecutive days.

Первичные конечные точки

• Evaluation of PK parameters of HS-10506: Cmax [Срок оценки: 120 hours after administration of HS-10506]
• Evaluation of PK parameters of HS-10506: AUC0-t [Срок оценки: 120 hours after administration of HS-10506]
• Evaluation of PK parameters of HS-10506: AUC0-∞ [Срок оценки: 120 hours after administration of HS-10506]

Вторичные конечные точки (12)

• Evaluation of PK parameters of HS-10506:Tmax [Срок оценки: 120 hours after administration of HS-10506]
• Evaluation of PK parameters of HS-10506: t1/2z [Срок оценки: 120 hours after administration of HS-10506]
• Evaluation of PK parameters of HS-10506: λz [Срок оценки: 120 hours after administration of HS-10506]
• Evaluation of PK parameters of HS-10506: CL/F [Срок оценки: 120 hours after administration of HS-10506]
• Evaluation of PK parameters of HS-10506: Vz/F [Срок оценки: 120 hours after administration of HS-10506]
• Evaluation of PK parameters of HS-10506: MRT0-t [Срок оценки: 120 hours after administration of HS-10506]
• Evaluation of PK parameters of HS-10506: MRT0-∞ [Срок оценки: 120 hours after administration of HS-10506]
• Adverse events [Срок оценки: through study completion, an average of 36 days]
• blood pressure [Срок оценки: through study completion, an average of 36 days]
• Pulse [Срок оценки: through study completion, an average of 36 days]
• body temperature [Срок оценки: through study completion, an average of 36 days]
• oxygen saturation [Срок оценки: through study completion, an average of 36 days]

Критерии участия

Критерии включения

• Sign the informed consent form before the trial, fully understand the trial content, procedures, and possible adverse events, and self-report the ability to complete the study in accordance with the trial regulations;
• Adult males and females (aged between 18 and 45 years, inclusive of boundary values, calculated on the date of signing the informed consent form);
• Participant's Body Mass Index (BMI) = weight (kg) / height² (m²) within the range of 19.0-26.0 kg/m² (inclusive of boundary values); male participants weigh ≥ 50 kg, female participants weigh ≥ 45 kg;
• Agree to practice highly effective contraception from the signing of the informed consent form until 3 months after the last dose, and have no plans for pregnancy or sperm/egg donation during this period (only non-drug contraceptive measures are permitted during the trial).

Критерии исключения

• Those with clinically significant abnormalities in physical examination, vital signs, oxygen saturation, 12-lead electrocardiogram, clinical laboratory tests, etc., deemed by the investigator as unsuitable for enrollment;
• Positive results for any one or more of hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus antibody, or Treponema pallidum(TP)specific antibody during the screening period;
• 12-lead electrocardiogram results during the screening period showing QTcF>450.00 ms for males or QTcF>470.00 ms for females;
• Previous or current presence of severe diseases of the nervous system, psychiatric system, digestive system, circulatory system, respiratory system (e.g., anatomical abnormalities of the airway, congenital microstomia with macroglossia, mandibular hypoplasia; chronic obstructive pulmonary disease or sleep apnea syndrome), urinary system, endocrine and metabolic system, immune system, hematological system, etc., assessed by the investigator as unsuitable for participation in this study;
• Current or past history of psychiatric disorders or brain dysfunction, or assessment of suicide risk using the Columbia-Suicide Severity Rating Scale (C-SSRS), or self-injurious behavior or suicide attempt within one year before screening, or current suicide risk based on the investigator's clinical judgment;
• Current or past history of severe gastrointestinal diseases (e.g., Crohn's disease, ulcerative colitis, reflux esophagitis, etc.);
• Evidence of previous ventricular dysfunction, such as congestive heart failure (CHF)or a history of CHF;
• History of surgery within 3 months before screening, or planned surgery during the trial period, or surgery that may affect drug absorption, distribution, metabolism, or excretion, deemed by the investigator as unsuitable for enrollment;
• Participation in any other clinical trial involving any investigational drug or device within 3 months before screening, or within 7 half-lives of another investigational drug before screening, whichever is longer;
• Prone to allergic reactions, or allergic constitution(e.g., allergies to pollen, two or more drugs/foods), or known allergy to components of HS-10506 tablets or itraconazole capsules;
• History of drug abuse, drug dependence, or use of illicit drugs within 5 years before screening, or positive drug abuse screening results;
• Frequent alcohol consumption within 3 months before screening (i.e., consuming more than 14 units of alcohol per week; 1 unit = 14 g alcohol, equivalent to 360 mL beer or 45 mL spirits with 40% alcohol content or 150 mL wine, equivalent to 10 bottles of beer, 500 mL spirits, or 3 bottles of wine per week), or inability to stop consuming alcoholic products during the trial, or positive alcohol breath test;
• Average daily smoking of more than 5 cigarettes within 3 months before screening, or inability to stop using any tobacco products during the trial;
• Excessive consumption of tea, coffee, and/or caffeinated beverages within 3 months before screening (average of more than 8 cups per day; 1 cup = 200 mL);
• Significant blood loss(≥200 mL)or blood donation within 3 months before screening, or plans for blood donation during the study or within 3 months after the study;
• Use of any drugs affecting CYP3A, CYP2C19 enzymes, or drugs altering gastric acid \[proton pump inhibitors (PPIs), H2 receptor antagonists, topical antacids, oral alkaline drugs, etc.\] within 30 days before the first dose of investigational product(or within 7 times the corresponding elimination half-life, whichever is longer);
• Use of any prescription drugs, over-the-counter drugs, herbal medicines, or health supplements(excluding topical preparations with local effects) within 14 days before the first dose of investigational product, or use of any drug within 7 half-lives (whichever is longer);
• Consumption of grapefruit or grapefruit products within 48 hours before the first dose of investigational product;
• Vaccination within 30 days before the first dose of investigational product, or planned use of vaccines during the study or within two weeks after the study;
• Significant changes in diet or sleep habits within 4 weeks before screening, assessed by the investigator as unsuitable for participation in this study;
• Female participants who are pregnant, breastfeeding, or have a positive pregnancy test result within 1 month before screening or during the trial period;
• Unprotected sexual intercourse within 14 days before screening;
• Special dietary requirements, inability to comply with a unified diet, or difficulty swallowing;
• Intolerance to venipuncture/indwelling needle blood collection or fear of needles/blood;
• Inability to complete the study for other reasons or deemed unsuitable for participation by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Qilu Hospital of Shandong University — Цзинань

Идентификаторы

NCT: NCT07535970 · HS-10506-113

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗