A Randomized, Open-Label, Crossover Phase 1 Clinical Trial to Evaluate the Relative Bioavailability and Food Effect of a New Formulation of HBW-3220 Capsules in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 21
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of HBW-3220
研究概览
简要总结
This Phase 1 study will evaluate a new formulation of HBW-3220 capsules in healthy adults. It will compare how much and how quickly HBW-3220 enters the bloodstream after a single 120 mg dose of the new formulation versus the previous formulation under fasting conditions, and after the new formulation is taken under fed versus fasting conditions. Twenty-one participants will be randomly assigned to one of three treatment sequences and will receive all three treatments during three study periods, with at least 7 days between doses. Blood samples will be collected for pharmacokinetic analysis, and safety and tolerability will be assessed throughout the study and during follow-up.
详细描述
HBW-3220 is a reversible Bruton tyrosine kinase (BTK) inhibitor. This is a randomized, open-label, three-period, three-sequence crossover Phase 1 study in 21 healthy adult participants.
Participants will be randomized in a 1:1:1 ratio to one of three treatment sequences. During each study period, participants will receive a single 120 mg oral dose of one of the following treatments: the previous formulation of HBW-3220 capsules under fasting conditions, the new formulation under fasting conditions, or the new formulation after a high-fat, high-calorie meal. Each participant will receive all three treatments, with a washout period of at least 7 days between doses.
Blood samples for pharmacokinetic assessment will be collected before dosing and through 72 hours after each dose. The primary pharmacokinetic parameters include maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t), and area under the curve extrapolated to infinity (AUC0-inf). Relative bioavailability will be assessed by comparing the new and previous formulations under fasting conditions. The effect of food will be assessed by comparing the new formulation under fed and fasting conditions.
Safety and tolerability will be evaluated using adverse events, vital signs, physical examinations, clinical laboratory tests, and 12-lead electrocardiograms. A safety follow-up will be conducted 10 ± 2 days after the last dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The participant has provided written informed consent before any study-related activity, fully understands the purpose and significance of the study, and is willing to comply with the study protocol.
- •Aged 18 to 55 years, inclusive.
- •Male participants must weigh at least 50.0 kg, and female participants must weigh at least 45.0 kg. Body mass index (BMI) must be between 19.0 and 26.0 kg/m2, inclusive.
- •Able to tolerate a high-fat meal.
- •No unprotected sexual intercourse within 2 weeks before screening. Participants must have no plans for conception and must agree to use effective contraceptive measures from screening until 3 months after the last dose of the study drug.
排除标准
- •History or current presence of any clinically significant disease involving the circulatory, endocrine, nervous, digestive, respiratory, genitourinary, hematologic, immune, psychiatric, or metabolic systems, or any other disease that may interfere with the study results, including but not limited to deep vein thrombosis, pulmonary embolism, bleeding disorders, or poorly controlled infection.
- •History of allergy to drugs, food, or other substances, or known hypersensitivity to any component or excipient of HBW-3220 capsules.
- •Unable to tolerate venipuncture, difficult venous access, or a history of fainting during needle insertion or blood collection.
- •Surgery within 3 months before the study or planned surgery during the study.
- •Use of any medication or health supplement, including Chinese herbal medicines, within 14 days before the study.
- •Use of any medication that inhibits or induces hepatic drug metabolism within 30 days before the study, including but not limited to inducers such as barbiturates, carbamazepine, phenytoin, glucocorticoids, and omeprazole, or inhibitors such as selective serotonin reuptake inhibitors, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, fluoroquinolones, and antihistamines.
- •Participation in another clinical trial involving administration of an investigational drug within 3 months before the study.
- •Blood donation or significant blood loss of 200 mL or more, excluding menstrual blood loss, blood transfusion, or use of blood products within 3 months before enrollment.
- •Pregnant or breastfeeding women, or participants unable or unwilling to use one or more non-pharmacological contraceptive measures during the study.
- •Special dietary requirements, inability to comply with the standardized diet, or difficulty swallowing.
- •Consumption of more than 8 cups of tea, coffee, and/or caffeine-containing beverages per day, with 1 cup defined as 250 mL.
- •Positive nicotine test before the first dose, smoking more than 5 cigarettes per day within 3 months before the study, or inability to abstain from all tobacco products during the study.
- •Positive alcohol test before the first dose; regular alcohol consumption within 6 months before the study, defined as more than 14 units of alcohol per week, where 1 unit equals 360 mL of beer, 45 mL of spirits containing 40% alcohol, or 150 mL of wine; or inability to abstain from alcohol-containing products during the study.
- •Positive drug abuse screening before the first dose; use of soft drugs, such as marijuana, within 3 months before the study; or use of hard drugs, such as cocaine or phencyclidine, within 1 year before the study.
- •Abnormal vital signs, defined as systolic blood pressure below 90 mmHg or at least 140 mmHg, diastolic blood pressure below 60 mmHg or at least 90 mmHg, heart rate below 50 bpm or above 100 bpm; or clinically significant abnormalities in physical examination, electrocardiogram, chest X-ray, abdominal ultrasound, or laboratory examinations, as determined by the investigator.
- •Positive test for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or Treponema pallidum antibody.
- •Presence or history of cardiac disease, including but not limited to congenital long QT syndrome, torsades de pointes, or risk factors for torsades de pointes, such as cardiac insufficiency, hypokalemia, or a family history of long QT syndrome; current use of Class IA antiarrhythmic drugs, such as quinidine or procainamide, Class III antiarrhythmic drugs, such as amiodarone or sotalol, or other drugs known to affect the QT interval; or a screening Fridericia-corrected QT interval (QTcF) of at least 450 ms for males or at least 460 ms for females, PR interval greater than 200 ms, or QRS interval of at least 120 ms.
- •Receipt of any live vaccine within 30 days before the first dose.
- •Consumption of grapefruit-containing products or other beverages or foods that may affect drug absorption, distribution, metabolism, or excretion within 48 hours before the first dose.
- •Any other condition that, in the investigator's opinion, may prevent the participant from completing the study or make the participant unsuitable for enrollment.
研究组 & 干预措施
Sequence A: Old Fasted - New Fasted - New Fed
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the old formulation under fasting conditions. In Period 2, participants receive the new formulation under fasting conditions. In Period 3, participants receive the new formulation after a high-fat, high-calorie meal. The washout period between doses is at least 7 days.
干预措施: HBW-3220 Old Formulation Under Fasting Conditions (Drug)
Sequence A: Old Fasted - New Fasted - New Fed
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the old formulation under fasting conditions. In Period 2, participants receive the new formulation under fasting conditions. In Period 3, participants receive the new formulation after a high-fat, high-calorie meal. The washout period between doses is at least 7 days.
干预措施: HBW-3220 New Formulation Under Fasting Conditions (Drug)
Sequence A: Old Fasted - New Fasted - New Fed
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the old formulation under fasting conditions. In Period 2, participants receive the new formulation under fasting conditions. In Period 3, participants receive the new formulation after a high-fat, high-calorie meal. The washout period between doses is at least 7 days.
干预措施: HBW-3220 New Formulation Under Fed Conditions (Drug)
Sequence B: New Fasted - New Fed - Old Fasted
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the new formulation under fasting conditions. In Period 2, participants receive the new formulation after a high-fat, high-calorie meal. In Period 3, participants receive the old formulation under fasting conditions. The washout period between doses is at least 7 days.
干预措施: HBW-3220 Old Formulation Under Fasting Conditions (Drug)
Sequence B: New Fasted - New Fed - Old Fasted
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the new formulation under fasting conditions. In Period 2, participants receive the new formulation after a high-fat, high-calorie meal. In Period 3, participants receive the old formulation under fasting conditions. The washout period between doses is at least 7 days.
干预措施: HBW-3220 New Formulation Under Fasting Conditions (Drug)
Sequence B: New Fasted - New Fed - Old Fasted
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the new formulation under fasting conditions. In Period 2, participants receive the new formulation after a high-fat, high-calorie meal. In Period 3, participants receive the old formulation under fasting conditions. The washout period between doses is at least 7 days.
干预措施: HBW-3220 New Formulation Under Fed Conditions (Drug)
Sequence C: New Fed - Old Fasted - New Fasted
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the new formulation after a high-fat, high-calorie meal. In Period 2, participants receive the old formulation under fasting conditions. In Period 3, participants receive the new formulation under fasting conditions. The washout period between doses is at least 7 days.
干预措施: HBW-3220 Old Formulation Under Fasting Conditions (Drug)
Sequence C: New Fed - Old Fasted - New Fasted
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the new formulation after a high-fat, high-calorie meal. In Period 2, participants receive the old formulation under fasting conditions. In Period 3, participants receive the new formulation under fasting conditions. The washout period between doses is at least 7 days.
干预措施: HBW-3220 New Formulation Under Fasting Conditions (Drug)
Sequence C: New Fed - Old Fasted - New Fasted
Participants receive a single oral dose of HBW-3220 120 mg (four 30 mg capsules) in each of three treatment periods. In Period 1, participants receive the new formulation after a high-fat, high-calorie meal. In Period 2, participants receive the old formulation under fasting conditions. In Period 3, participants receive the new formulation under fasting conditions. The washout period between doses is at least 7 days.
干预措施: HBW-3220 New Formulation Under Fed Conditions (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of HBW-3220
时间窗: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 72 hours after dosing in each of the three treatment periods
Maximum observed plasma concentration of HBW-3220 will be calculated from plasma concentration-time data using noncompartmental analysis. Cmax will be compared between the new and old formulations under fasting conditions and between the fed and fasting conditions for the new formulation.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of HBW-3220
时间窗: Predose through 72 hours after dosing in each of the three treatment periods
AUC0-t of HBW-3220 will be calculated from plasma concentration-time data using noncompartmental analysis. AUC0-t will be compared between the new and old formulations under fasting conditions and between the fed and fasting conditions for the new formulation.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of HBW-3220
时间窗: Predose through 72 hours after dosing in each of the three treatment periods
AUC0-inf of HBW-3220 will be calculated from plasma concentration-time data using noncompartmental analysis. AUC0-inf will be compared between the new and old formulations under fasting conditions and between the fed and fasting conditions for the new formulation.
次要结局
未报告次要终点
研究者
Guoping Yang
Professor of Clinical Pharmacology
The Third Xiangya Hospital of Central South University