A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of CBP-174 After Oral Administration
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Change in blood pressure
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of CBP-174 after a single oral dose in healthy adult subjects.
详细描述
This is a randomized, double-blind, placebo-controlled, single ascending dose study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of CBP-174 compared to placebo. The study plans to set 6 dose escalation cohorts with single oral dose. Each subject will receive only one dose regimen in this study and the total duration to participate the study is approximately 1 to 4-week.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Subjects will be enrolled into the study only if they meet ALL of the following inclusion criteria:
- •Subjects are fully informed of the study, and are willing to participate in the study and sign the informed consent document prior to any procedure
- •Healthy male and female subjects, aged 18 to 55 years (both inclusive)
- •Body mass index is between 18 and 32 kg/m2 (both inclusive), the weight of male subjects ≥ 50 kg, the weight of female subjects ≥ 45 kg
- •Considered generally normal or abnormal with no clinical significance upon medical history, physical examination, vital signs, ECG, and clinical laboratory tests, as judged by the Investigator
- •Female subjects of child-bearing potential must agree to use highly effective contraceptive methods 1 month before the screening, during the entire study, and within 3 months after the end of this study, and have no egg donation plan within 3 months of study end. The male partner of a female subject must agree to use condoms during the screening, entire study, and within 3 months after the end of this study. Male subjects considered fertile must agree to not plan to father a child, donate sperm, and take effective contraceptive methods during the screening, entire study, and within 3 months after the end of this study. The female partner of male subjects must agree to use a highly effective method of female contraception (Section 9.8.3.2) during the screening, entire study, and within 3 months after the end of this study. Contraceptive requirements applies to subjects in same sex relationships for male and female subjects, female subjects of non child bearing potential or male subjects with female partners of non-childbearing potential.
- •Subjects who are able to communicate well with Investigators, as well as understand and adhere to the requirements of this study
排除标准
- •Subjects will be excluded from the study, if they meet ANY of the following criteria:
- •Subjects will be excluded from the study, if they meet ANY of the following criteria:
- •Subjects who have difficulties in venous blood collection or history of dizziness with blood or needles
- •Female subjects who have a positive pregnancy test or are breastfeeding
- •Subjects who have allergy/hypersensitivity history to any excipient of CBP-174 solution, or hypersensitivity to antihistamines, or severe allergies at the discretion of Investigator
- •Exposure to any other investigational medicinal product or any other clinical trial within 30 days or 5 times half-lives (whichever is longer) before dosing current study medication
- •Subjects who have a history of gastrointestinal (such as duodenal ulcer, alimentary tract hemorrhage, etc.), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
- •Subjects who have a history of significant eye diseases (such as keratitis, and scleritis, etc.) or clinical significant eye signs (conjunctiva hyperemia, etc.)
- •Subjects who have a history of attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD)
- •Subjects who have a history of sleep disorders within 2 years before the screening visit or score highly on the PSQI or ISI questionaire; or have a history of epilepsy or other seizure disorder
- •*Pittsburgh Sleep Quality Index (PSQI) ≥ 8 or Insomnia Severity Index (ISI) ≥ 8
- •Subjects who have the medical history of other significant diseases (including but not limited to pulmonary, cardiovascular, gastrointestinal, hematological endocrinological, immunological, dermatological, malignant diseases, mental and nervous systems, and other related diseases) or any other disease/ailment at the discretion of the Investigator
- •Subjects with any of the following clinical laboratory tests results at screening:
- •a Aspartate aminotransferase (AST) > 1.5 × the upper limit of normal (ULN)
- •b Alanine aminotransferase (ALT) > 1.5 × ULN
- •c Serum creatinine > 1.2 × ULN; or creatinine clearance < 60 mL/min (calculated by the Cockcroft-Gault)
- •*The clinical laboratory tests of hematology, blood biochemistry, or urinalysis could be allowed repeat once if Investigator considers it necessary
- •Subjects whose QTcF interval prolongation at screening (male: QTcF interval ≥ 450 ms, female: QTcF interval ≥ 470 ms)
- •Blood donation or blood loss more than 400 mL within 3 months before the screening visit
- •Subjects with a known history of drug abuse within 2 years before the screening visit; or positive drug abuse at screening
- •Weekly alcohol consumption of more than 14 units of alcohol (1 unit of alcohol = 360 mL of beer or 45 mL of spirit with the alcohol content of 40% or 150 mL of wine) in any week within the past 3 months before the screening visit; or intake of alcohol-containing products within 48 hours before the first dose, or cannot abstain from any alcohol product during the study, or positive breath alcohol test at screening or check-in (Day -1）
- •Smoking history (> 5 cigarettes per day) within 3 months before the screening visit, or cannot abstain from any tobacco products during the study, or positive urine nicotine test before randomization
- •Excessive drinking of tea, coffee, or caffeine-containing beverage (at least 8 cups per day, 1 cup = 250 mL) any day within 3 months before screening; intake of rich caffeine- or xanthine-containing food or drinks that may produce caffeine or xanthine after being metabolized (eg, coffee, tea, chocolate, cola drinks) within 48 hours before the first dose
- •Any marketed medication (prescription and nonprescription drugs) within 14 days before the first dose or within 5 times the elimination half-life or pharmacodynamic half-life of the medication (excluding oral contraceptives and low dose paracetamol at the discretion of the Investigator, or topical ointments at the discretion of the Investigator)
- •Administration of a Coronavirus Disease 2019 (COVID-19) vaccine in the past 14 days prior to dosing
- •Use of herbal medicines, dietary supplements and vitamin within 14 days before the first dose(permissible at the discretion of the Investigator)
- •Subjects who have a major surgery within 3 months before the first dose or who plan to undergo surgery during the study
- •Positive screening test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody
- •Subjects who are determined as not eligible to participate in this study by the Investigator
研究组 & 干预措施
CBP-174
CBP-174 oral solution
干预措施: CBP-174 (Drug)
Placebo
placebo oral solution
干预措施: Placebo (Drug)
结局指标
主要结局
Change in blood pressure
时间窗: Up to 7 days post dosing
Blood pressure measured in mmHg
Change in respiratory rate
时间窗: Up to 7 days post dosing
respiratory rate measured in breaths per minute
Change in pulse rate
时间窗: Up to 7 days post dosing
Pulse rate measured per minute
Change in tympanic temperature
时间窗: Up to 7 days post dosing
tympanic temperature measured in celsius
Incidence of adverse events and serious adverse events
时间窗: Up to 7 days post dosing
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary.
Severity of adverse events and serious adverse events
时间窗: Up to 7 days post dosing
The investigator may use the CTCAE V5.0 to assist in the determination of severity and clinical significance.
Clinically significant abnormality in physical examinations
时间窗: Up to 7 days post dosing
Physical examinations includes examination in cutaneous, lymph node, head (especially of eyes) and neck, chest, abdomen, musculoskeletal and nervous systems.
Clinically significant change in heart rate
时间窗: Up to 7 days post dosing
Heart rate in beats per minute (Bpm) through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.
Clinically significant change in RR interval
时间窗: Up to 7 days post dosing
R-R interval measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.
Clinically significant change in PR interval
时间窗: Up to 7 days post dosing
P-R interval measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.
Clinically significant change in QRS complex
时间窗: Up to 7 days post dosing
QRS complex measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.
Clinically significant change in QT interval
时间窗: Up to 7 days post dosing
QT interval measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.
Clinically significant change in Fridericia's Correction QT (QTcF) interval
时间窗: Up to 7 days post dosing
QTcF interval measured in millisecond through 12-lead ECG assessment. The Investigator or designee will be responsible for review and interpretation of safety ECGs on site.
Clinically significant abnormal laboratory value in Total Protein (TB)
时间窗: Up to 7 days post dosing
Measured in g/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Albumin (ALB)
时间窗: Up to 7 days post dosing
Measured in g/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Alanine aminotransferase (ALT)
时间窗: Up to 7 days post dosing
Measured in IU/L. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Aspartate aminotransferase (AST)
时间窗: Up to 7 days post dosing
Measured in IU/L. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Alkaline phosphatase (ALP/AKP)
时间窗: Up to 7 days post dosing
Measured in IU/L. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in percentage of Eosinophils
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Potassium
时间窗: Up to 7 days post dosing
Measured in mmol/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Glutamyl transpeptidase
时间窗: Up to 7 days post dosing
Measured in U/L. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Total bilirubin
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Direct Bilirubin
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in percentage of Basophils
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Indirect Bilirubin
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Glucose
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Urea
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Uric Acid
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Creatinine
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Creatine Kinase
时间窗: Up to 7 days post dosing
Measured in IU/L. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in percentage of Monocytes
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Sodium
时间窗: Up to 7 days post dosing
Measured in mmol/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Chloride
时间窗: Up to 7 days post dosing
Measured in mmol/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Calcium
时间窗: Up to 7 days post dosing
Measured in mmol/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Total Cholesterol
时间窗: Up to 7 days post dosing
Measured in mmol/L. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal laboratory value in Blood Triglycerides
时间窗: Up to 7 days post dosing
Measured in mmol/L. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Leukocyte Count
时间窗: Up to 7 days post dosing
Counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Neutrophil count
时间窗: Up to 7 days post dosing
Counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Lymphocyte count
时间窗: Up to 7 days post dosing
Counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Monocytes count
时间窗: Up to 7 days post dosing
Counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Eosinophils count
时间窗: Up to 7 days post dosing
Counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Basophil count
时间窗: Up to 7 days post dosing
Counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in percentage of Neutrophil
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in percentage of Lymphocyte
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Erythrocyte count
时间窗: Up to 7 days post dosing
Counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Hemoglobin
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Hematocrit
时间窗: Up to 7 days post dosing
Measured in %. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Platelets
时间窗: Up to 7 days post dosing
Counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal finding in Urine Occult Blood
时间窗: Up to 7 days post dosing
Urine Occult Blood will be record as positive or negative. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urine Bilirubin
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urine pH
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urine Protein
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urine Glucose
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urine Specific gravity
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urine Ketones
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urobilinogen
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urinary leukocyte
时间窗: Up to 7 days post dosing
Urinary leukocyte will be counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urine erythrocytes
时间窗: Up to 7 days post dosing
Urine erythrocytes will be counted in K/uL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Urine Nitrites
时间窗: Up to 7 days post dosing
Measured in mg/dL. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Prothrombin time (PT)
时间窗: Up to 7 days post dosing
Measured in seconds by coagulation tests. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Activated partial thromboplastin time (APTT)
时间窗: Up to 7 days post dosing
Measured in seconds by coagulation tests. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in International normalized ratio (INR)
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Fibrinogen (FIB)
时间窗: Up to 7 days post dosing
Measured in mmol/L. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal change in Thrombin time (TT)
时间窗: Up to 7 days post dosing
Measured in seconds by coagulation tests. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal in Feces colour
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal in Feces properties
时间窗: Up to 7 days post dosing
The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal in Fecal Red blood cell
时间窗: Up to 7 days post dosing
Measured in Units. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal in Fecal Occult blood
时间窗: Up to 7 days post dosing
Recorded as positive or negative. The physician will judge whether an abnormality is clinically significant.
Clinically significant abnormal in Fecal White blood cell
时间窗: Up to 7 days post dosing
Measured in Units. The physician will judge whether an abnormality is clinically significant.
次要结局
- AUC0-72 h: Area under the plasma concentration-time curve of CBP-174 from time 0 to 72h(Up to 72 hours post dosing)
- Cmax: Maximum observed concentration(Up to 72 hours post dosing)
- T1/2: Elimination half-life;(Up to 72 hours post dosing)
- CL/F: Apparent clearance;(Up to 72 hours post dosing)
- %AUCex: Percentage of AUC0-∞ obtained by extrapolation(Up to 72 hours post dosing)
- AUC0-∞: Area under the plasma concentration-time curve of CBP-174 from time 0 to infinity(Up to 72 hours post dosing)
- Tmax: Time to maximum concentration;(Up to 72 hours post dosing)
- λz: Terminal phase rate constant;(Up to 72 hours post dosing)
- V/F: Apparent Volume;(Up to 72 hours post dosing)