A Phase 1, First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered IPG1094 in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 2
- 主要终点
- albumin (ALB)
研究概览
简要总结
This is a phase 1, first-in-human, randomized, double-blind, placebo-controlled, single dose escalation study to evaluate the safety, tolerability, and PK of single dose orally administered IPG1094 in healthy adult participants.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must meet all of the following criteria to be included in the study:
- •Healthy adult male or female participants between 18 and 50 years of age (inclusive).
- •Body weight between 50 and 100 kg (inclusive) and body mass index (BMI) within 18~32 kg/m2 (inclusive).
- •Health status
- •In good health as determined by screening tests. Good health is defined as having no clinically relevant abnormalities identified by a detailed medical history, full physical examination (including measurement of blood pressure and pulse rate), 12-lead ECG, and clinical laboratory tests.
- •Vital signs (measured after resting for 5 minutes seated position) within normal range, or outside the normal range and not considered clinically significant by the Investigator.
- •Standard 12-lead ECG parameters (recorded after resting for 5 minutes in supine position) in the following ranges; corrected QT interval(QTc) (Fridericia algorithm recommended) ≤ 450 ms for males and 470 ms for females, and normal ECG tracing, or abnormal ECG tracing not considered clinically relevant by the Investigator.
- •Laboratory parameters demonstrating no clinically significant abnormalities, as determined by the Investigator. A total bilirubin outside the normal range may be acceptable if total bilirubin does not exceed 1.5 × upper limit of normal(ULN) conjugated bilirubin (with the exception of a participant with documented Gilbert syndrome).
- •A negative result on urine drug screen and a repeat negative result on Day -1 (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
- •Female participants must not be pregnant or breastfeeding and must use an effective contraception method (as described in Section 4.5.4), with the exception of participants who have undergone sterilization in the preceding 3 months, or who are postmenopausal.
- •A woman of childbearing potential (WOCBP) must undergo pregnancy testing prior to the first dose of the Investigational Medicinal Product (IMP). The participant must be excluded from the study if the serum pregnancy test is positive.
- •A postmenopausal state is defined as 12 months of amenorrhea without an alternative medical cause. In the absence of 12 months of amenorrhea, menopause may be confirmed by follicle stimulating hormone（FSH） measurement (> 40 IU/L or milli-International unit（mIU）/mL).Females on Hormonal Replacement therapy (HRT ), where menopausal status is indeterminate, will be required to use a non-estrogen hormonal contraceptive method if participants wish to continue their HRT during the study. Participants must otherwise discontinue HRT to allow for confirmation of postmenopausal status prior to enrollment in the study.
- •Provide written informed consent prior to undertaking any study-related procedures.
- •Must not be under any administrative or legal supervision or under institutionalization as per a regulatory or juridical order.
排除标准
- •Participants who meet any of the following criteria will be excluded from the study:
- •Medical history and clinical status
- •Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, musculoskeletal, rheumatological, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness.
- •Frequent severe headaches and/or migraines, recurrent nausea and/or vomiting (defined as vomiting more than twice a month).
- •Made a blood donation of any volume within 2 months prior to the first dose.
- •Symptomatic postural hypotension, irrespective of actual decrease in blood pressure, or asymptomatic postural hypotension with a decrease in systolic blood pressure ≥30 mmHg within 3 minutes of moving from supine to standing position.
- •Presence or history of drug hypersensitivity, or anaphylactic reaction, diagnosed and treated by a physician.
- •Known hypersensitivity to any component of the IMP formulation.
- •History or presence of drug or alcohol abuse (defined as alcohol consumption more than 2 units per day on a regular basis).
- •Regular smoking (defined as more than 5 cigarettes or equivalent per week), or unable to stop smoking during the study. Occasional smokers may be enrolled.
- •Excessive consumption of beverages containing xanthine bases (defined as more than 4 glasses per day).
- •Interfering substances
- •Any medication, including St John's Wort, within 14 days prior to administration of the first dose or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, with the exception of hormonal contraception, menopausal hormone replacement therapy, or occasional paracetamol at doses up to 2g/day.
- •Any consumption of grapefruit or products containing grapefruit within 5 days prior to the first dose administration.
- •Any vaccination in the 28 days prior to administration of the first dose.
- •General conditions
- •Any participant who, in the judgment of the Investigator, is likely to be non-compliant during the study, or to be unable to cooperate due to language problems or poor mental development.
- •Any participant who enrolled in or participated in any other clinical study involving an investigational medicinal product, or in any other type of medical research within 1 month or within 5 times the elimination half-life prior to administration of the first dose.
- •Any participant who cannot be contacted in the case of an emergency.
- •Any participant who is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff thereof directly involved in conducting the study or any person dependent on (employees or immediate family members) the study site, the Investigator or the Sponsor.
- •Biological status
- •Positive result on any of the following tests: hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBcAb), anti-hepatitis C virus antibodies (anti-HCV), anti-human immunodeficiency virus 1 and 2 antibodies（anti-HIV1 and anti-HIV2 Ab).
- •Positive alcohol test.
- •Any participant in whom venous blood collection is difficult.
研究组 & 干预措施
IPG1094 100 mg SAD
Four subjects in this cohort will receive a single dose of IPG1094 100 mg and two subjects will receive a single dose of placebo 100 mg orally.
干预措施: IPG1094 100 mg SAD (Drug)
IPG1094 300 mg SAD
Six subjects in this cohort will receive a single dose of IPG1094 300 mg and two subjects will receive a single dose of placebo 300 mg orally.
干预措施: IPG1094 300 mg SAD (Drug)
IPG1094 600 mg SAD
Six subjects in this cohort will receive a single dose of IPG1094 600 mg and two subjects will receive a single dose of placebo 600mg orally.
干预措施: IPG1094 600 mg SAD (Drug)
IPG1094 900mg SAD
Six subjects in this cohort will receive a single dose of IPG1094 900 mg qd and two subjects will receive a single dose of placebo 900mg qd orally.
干预措施: IPG1094 900 mg SAD (Drug)
IPG1094 1200mg SAD
Six subjects in this cohort will receive a single dose of IPG1094 1200 mg and two subjects will receive a single dose of placebo 1200 mg orally.
干预措施: IPG1094 1200 mg SAD (Drug)
IPG1094 600 mg MAD QD
Dosing begins on Day 1 and continues for 10 days with daily doses of 600 mg QD. Subjects are discharged on Day 14, followed by a 7-day post-dosing follow-up. Six subjects in this cohort will receive IPG1094 600 mg and two subjects will receive placebo.
干预措施: IPG1094 600 mg MAD QD (Drug)
IPG1094 200 mg MAD BID
Dosing begins on Day 1 and continues for 10 days with twice daily 200 mg. Subjects are discharged on Day 14, followed by a 7-day post-dosing follow-up. Six subjects in this cohort will receive IPG1094 200 mg nd two subjects will receive placebo.
干预措施: IPG1094 200 mg MAD BID (Drug)
IPG1094 300 mg MAD BID
Dosing begins on Day 1 and continues for 10 days with twice daily 300 mg. Subjects are discharged on Day 14, followed by a 7-day post-dosing follow-up. Six subjects in this cohort will receive IPG1094 300 mg and two subjects will receive placebo.
干预措施: IPG1094 300 mg MAD BID (Drug)
IPG1094 300 mg Fasted-Fed
For Cohort FE-1, Six subjects administration of a single dose of IPG1094 would occur on Day 1 of Period 1 under the fasted condition, and Day 5 (anticipated) of Period 2 under the fed condition. 300 mg per administration.
干预措施: IPG1094 300 mg Fasted-Fed (Drug)
Part D IPG1094 300 mg Fed-Fasted
For Cohort FE-2, Six subjects administration of a single dose of IPG1094 would occur on Day 1 of Period 1 under the fed condition, and Day 5 (anticipated) of Period 2 under fasted condition. 300 mg per administration.
干预措施: IPG1094 300 mg Fed-Fasted (Drug)
结局指标
主要结局
albumin (ALB)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
alkaline phosphatase (ALP)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
creatinine (Cr)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
Standard 12-lead ECG - heart rate
时间窗: Up to 8 days
Evaluation of Electrocardiograms
Standard 12-lead ECG - PR
时间窗: Up to 8 days
Evaluation of Electrocardiograms
Pulse rate
时间窗: Up to 8 days
Evaluation of Vital Signs
Urea
时间窗: Up to 8 days
Evaluation of Serum Chemistry
Occurrence of all adverse events
时间窗: Up to 8 days
Evaluation of adverse events
white blood cell count (WBC)
时间窗: Up to 8 days
Evaluation of Hematology
mean corpuscular hemoglobin concentration
时间窗: Up to 8 days
Evaluation of Hematology
platelet count (PLT)
时间窗: Up to 8 days
Evaluation of Hematology
haemoglobin (HGB)
时间窗: Up to 8 days
Evaluation of Hematology
mean corpuscular volume (MCV)
时间窗: Up to 8 days
Evaluation of Hematology
Alanine aminotransferase (ALT)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
total bilirubin (TBil)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
chloride (Cl)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
lactate dehydrogenase (LDH)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
phosphate (P)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
Blood pressure (both systolic and diastolic)
时间窗: Up to 8 days
Evaluation of Vital Signs
absolute differential leukocyte count (basophils)
时间窗: Up to 8 days
Evaluation of Hematology
Standard 12-lead ECG - QT
时间窗: Up to 8 days
Evaluation of Electrocardiograms
total protein (TP)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
Prothrombin time (PT)
时间窗: Up to 8 days
Evaluation of Serum Coagulation
RBC
时间窗: Up to 8 days
Evaluation of Hematology
Hematocrit
时间窗: Up to 8 days
Evaluation of Hematology
absolute differential leukocyte count (eosinophils)
时间窗: Up to 8 days
Evaluation of Hematology
absolute differential leukocyte count (lymphocytes)
时间窗: Up to 8 days
Evaluation of Hematology
Respiration rate
时间窗: Up to 8 days
Evaluation of Vital Signs
Standard 12-lead ECG - QTcF
时间窗: Up to 8 days
Evaluation of Electrocardiograms
calcium (Ca)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
creatine kinase (CK)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
mean corpuscular hemoglobin
时间窗: Up to 8 days
Evaluation of Hematology
absolute differential leukocyte count (monocytes)
时间窗: Up to 8 days
Evaluation of Hematology
absolute differential leukocyte count (neutrophils)
时间窗: Up to 8 days
Evaluation of Hematology
Temperature (°C )
时间窗: Up to 8 days
Evaluation of Vital Signs
Standard 12-lead ECG - QRS
时间窗: Up to 8 days
Evaluation of Electrocardiograms
aspartate aminotransferase (AST)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
cholesterol (CHO)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
international normalized ratio (INR)
时间窗: Up to 8 days
Evaluation of Serum Coagulation
glucose (Glu)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
potassium (K)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
activated partial thromboplastin time (APTT)
时间窗: Up to 8 days
Evaluation of Serum Coagulation
fibrinogen
时间窗: Up to 8 days
Evaluation of Serum Coagulation
pH
时间窗: Up to 8 days
Evaluation of Urinalysis
glucose (GLU)
时间窗: Up to 8 days
Evaluation of Urinalysis
nitrites (U-NIT)
时间窗: Up to 8 days
Evaluation of Urinalysis
specific gravity (U-SG)
时间窗: Up to 8 days
Evaluation of Urinalysis
sodium (Na)
时间窗: Up to 8 days
Evaluation of Serum Chemistry
Bilirubin (U-BIL)
时间窗: Up to 8 days
Evaluation of Urinalysis
urine erythrocytes (U-RBC)
时间窗: Up to 8 days
Evaluation of Urinalysis
ketones (U-KET)
时间窗: Up to 8 days
Evaluation of Urinalysis
protein (U-PRO)
时间窗: Up to 8 days
Evaluation of Urinalysis
Urinary leukocyte (U-LEU)
时间窗: Up to 8 days
Evaluation of Urinalysis
urobilinogen (URO)
时间窗: Up to 8 days
Evaluation of Urinalysis
Adverse Events
时间窗: Part A (SAD)：From signed ICF up to D8；Part B (MAD)：From signed ICF up to D17；Part C (MAD)：From signed ICF up to D17；Part D (FE)：From signed ICF up to D12；
Evaluation of adverse events
次要结局
- Area under the serum concentration-time curve (AUC[0-t](Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.)
- Time to Cmax (tmax)(Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.)
- Apparent terminal phase half-life (t1/2)(Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.)
- Maximum plasma concentration（Cmax）(Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.)
- Area under the serum concentration-infinity curve AUC[0-infinity](Blood samples will be collected at 0 h before administration (within 1h prior to administration), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, 24, 36, 48, 72, and 96 h after administration.)
- Cmax(Part A: UP to D5 Part B: UP to D14 Part C: Up to D13 Part D: UP to D12)
- Tmax(Part A: UP to D5 Part B: UP to D14 Part C: Up to D13 Part D: UP to D12)
- AUC0-t(Part A: UP to D5 Part B: UP to D14 Part C: Up to D13 Part D: UP to D12)
- CL/F(Part A: UP to D5 Part B: UP to D14 Part C: Up to D13 Part D: UP to D12)