A Phase 1 Study to Evaluate the Tolerance, Safety, Pharmacokinetics and Pharmacodynamics of Oral Administration of SSS17 in Chinese Healthy Adult Subjects With Single and Multiple Dose Escalation and the Effect of Food on the Pharmacokinetics of SSS17.
试验速览
- 阶段
- 1 期
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Part 1: Maximum plasma concentration (Cmax) of SSS17
研究概览
简要总结
This study will investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of single oral administration of 5 mg, 15 mg, 20 mg and 25 mg of SSS17 compared with placebo, and evaluate the efficacy, safety, tolerance, pharmacokinetics and pharmacodynamics of multiple oral administration of 15 mg and 20 mg of SSS17 compared with placebo. In addition, the study will assess the effect of food on the pharmacokinetics of SSS17.
详细描述
The study will enroll healthy volunteers from a single academic medical center in China. All participants will be informed about the study and potential risks and required to provide written informed consent prior to undergoing study-related procedures.The study will be divided into 3 parts.
Part 1: Subjects will be allocated 2:8 to receive placebo or SSS17（it was only 2:2 in 5mg dose group）,which will be administered by oral route with single dose. At each dose, tolerability, safety, PK and PD characteristics will be investigated.
Part 2: Subjects will be allocated 2:8 to receive placebo or SSS17, which will be administered by oral route with multiple dose. At each cohort，tolerability, safety, PK and PD characteristics will be investigated.
Part 3: The subjects will receive two cycles of treatment, one is given on an empty stomach, the other is given after a high-fat meal, with an interval of 15 days.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Chinese healthy adult subjects aged 18-45 years (including the boundary value) at the time of signing the informed consent were male and female;
- •In the screening period, the weight of male subjects was more than or equal to 50.0 kg; Female weight ≥ 45.0 kg; Body mass index (BMI) ranged from 19.0 kg / m2 to 26.0 kg / m2 (including boundary value); BMI = weight kg / height m2);
- •Within 6 months from the date of signing the informed consent to the end of the trial, female subjects agreed to take reliable measures to avoid pregnancy and ensure no birth plan, while male subjects agreed to take reliable measures to avoid pregnancy and ensure no birth plan;
- •Willing to participate in the study and sign a written informed consent, able to communicate well with the researchers, and agreed to follow the requirements of the trial protocol and follow-up on schedule.
排除标准
- •Participated in other drug clinical trials within 3 months before screening;
- •Have any clinical history of serious diseases or are suffering from related diseases, including but not limited to digestive system (such as diarrhea, vomiting, inflammatory bowel disease, hemorrhoids, acute gastritis, peptic ulcer, acute and chronic gastrointestinal disorders with obvious digestive and absorption disorders), cardiovascular system, respiratory system, urinary system, musculoskeletal system, endocrine system, gastrointestinal tract diseases, etc Diseases of nervous and mental system, blood system, immune system, etc; A history of any disease or thrombotic disease or vascular malformation that increases the risk of bleeding; Patients with dysphagia;
- •Allergic constitution, known allergic to test drug ingredients or allergic history to any drug or food (mango, shrimp, crab, lobster, etc.) or pollen allergy history;
- •Those who smoke more than 5 cigarettes / day or the same amount of tobacco after inquiry, or who can not ban smoking during the trial period; Or alcohol consumption per week is equal to 14 units (1 units 25mL wine Baijiu / 100mL wine / 285mL beer), or those who can not prohibit alcohol during the test period;
- •Have a history of drug abuse or drug abuse;
- •Within 6 months, there were fertility planning, sperm donation and egg donation planning;
- •Patients with lactose intolerance (those who have had diarrhea after drinking milk);
- •Those who have special requirements for diet and cannot accept unified diet;
- •Blood donors or massive blood loss (≥ 400ml), EPO treatment, blood transfusion or use of blood products within 3 months before screening;
- •Those vaccinated within 8 weeks before screening or during the study period;
- •There was a history of acupuncture and blood sickness; Or with orthostatic hypotension;
- •Those who have participated in and used the trial drug;Those who have used any prescription drug, over-the-counter drug, Chinese herbal medicine, vitamins or health care products within 14 days before screening and whose time is less than 5 half-life of the drug or less than 2 weeks (whichever is the longest);
- •The serum pregnancy test of lactating and pregnant women, or female volunteers of childbearing age was positive;
- •The results of physical examination, chest X-ray, color Doppler ultrasound, electrocardiogram and laboratory examination were abnormal and clinically significant; Or hemoglobin of male subjects was more than 175.0 g / L; Or hemoglobin of female subjects was more than 150.0 g / L; Or hemoglobin of male and female were less than 113g / L;
- •Within 48 hours before enrollment, those who took any special diet that affected the absorption, distribution, metabolism and excretion of drugs, including pitaya, mango, grapefruit, lime, carambola or food or drink prepared from them, chocolate, and any food or drink containing caffeine;
- •Urine drug screening test was positive;
- •Alcohol breath test was positive within 24 hours before administration;
- •The researchers think that there are other cases that are not suitable for the trial.
研究组 & 干预措施
Part 1: Single Dose Escalation SSS17
Escalating doses of SSS17, single dose administration
干预措施: SSS17 (Drug)
Part 1: Single Dose Escalation matching Placebo
Escalating doses of matching placebo, single dose administration
干预措施: Placebo (Drug)
Part 2: Multiple Dose Escalation SSS17
Escalating doses of SSS17, multiple dose administration
干预措施: SSS17 (Drug)
Part 2: Multiple Dose Escalation matching Placebo
Escalating doses of matching placebo, multiple dose administration
干预措施: Placebo (Drug)
Part 3: Treatment Sequence 1 (A to B)
The subjects in the first cycle received oral administration of SSS17 on an empty stomach, and subjects in the second cycle received oral administration of SSS17 after a high-fat meal
干预措施: SSS17 (Drug)
Part 3: Treatment Sequence 2 (B to A)
The subjects in the first cycle received oral administration of SSS17 after a high-fat meal, and the subjects in the second cycle received oral administration of SSS17 on an empty stomach
干预措施: SSS17 (Drug)
结局指标
主要结局
Part 1: Maximum plasma concentration (Cmax) of SSS17
时间窗: Up to 336 hours post-dose
Plasma samples will be collected and Cmax will be assessed in the part 1
Part 1: Area under the concentration-time curve (AUC) of plasma concentration of SSS17
时间窗: Up to 336 hours post-dose
Plasma samples will be collected and the AUC from zero to infinity will be assessed in the part 1
Part 1: Time-to-Cmax (Tmax) of SSS 17
时间窗: Up to 336 hours post-dose
Plasma samples will be collected and the Tmax will be assessed from the concentration-time curve in the part 1
Part 1: Elimination terminal half-life (t1/2) of SSS17
时间窗: Up to 336 hours post-dose
Plasma samples will be collected and the t1/2 will be assessed in the part 1
Part 1: . Total amount of SSS17 excreted in urine over 72 hours (Ae0-72)
时间窗: Up to 72 hours post-dose
Urine sample will be collected at pre-specified intervals and Ae0-72 will be assessed in the part 1
Part 1: AEs
时间窗: Baseline up to Days 15
Assessment AEs by frequency and severity in the part 1
Part 1: Fraction of SSS17 excretion during each collection interval (Fe0-72)
时间窗: Up to 72 hours post-dose
Urine sample will be collected at pre-specified intervals and Fe0-72 will be assessed in the part 1
Part 1: Renal clearance (CLR) of SSS17
时间窗: Up to 72 hours post-dose
Urine sample will be collected at pre-specified intervals and CLR will be assessed in the part 1
Part 2: AEs
时间窗: Up to Days 33 or 57
Assessment AEs by frequency and severity in the part 2
Part 2: Steady state minimal concentration (Css_min) of SSS17
时间窗: Up to Days 33 or 57
Plasma samples will be collected and Css_min will be assessed in the part 2
Part 2: Steady state maximum concentration (Css_max) of SSS17
时间窗: Up to Days 33 or 57
Plasma samples will be collected and Css_max will be assessed in the part 2
Part 2: Steady state average concentration (Css_av) of SSS17
时间窗: Up to Days 33 or 57
Plasma samples will be collected and Css_av will be assessed in the part 2
Part 2: Area under the concentration-time curve of plasma concentration of SSS17 within the interval of administration after reaching steady state (AUC0-τ)
时间窗: Up to Days 33 or 57
Plasma samples will be collected and the AUC from zero to τ will be assessed
Part 3: Maximum plasma concentration (Cmax) of SSS17
时间窗: Up to Days 44
Plasma samples will be collected and Cmax will be assessed in the part 3
Part 3: Area under the concentration-time curve (AUC) of plasma concentration of SSS17
时间窗: Up to Days 44
Plasma samples will be collected and the AUC from zero to infinity will be assessed in the part 3
Part 3: Time-to-Cmax (Tmax) of SSS 17
时间窗: Up to Days 44
Plasma samples will be collected and the Tmax will be assessed from the concentration-time curve in the part 3
Part 3: Elimination terminal half-life (t1/2) of SSS17
时间窗: Up to Days 44
Plasma samples will be collected and the t1/2 will be assessed in the part 3
次要结局
- Part 1: EPO concentrations(Up to 168 hours post-dose)
- Part 1: VEGF concentrations(Up to 168 hours post-dose)
- Part 1: Change of Hgb from baseline(Baseline up to Days 15)
- Part 1: Change of hepcidin from baseline(Up to 168 hours post-dose)
- Part 1: Change of RTC from baseline(Baseline up to Days 15)
- Part 1: Change of RBC from baseline(Baseline up to Days 15)
- Part 2: EPO concentrations(Up to Days 33 or 57)
- Part 2: VEGF concentrations(Up to Days 33 or 57)
- Part 2: Change of hepcidin from baseline(Up to Days 33 or 57)
- Part 2: Change of RTC from baseline(Baseline up to Days 33 or 57)
- Part 2: Change of RBC from baseline(Baseline up to Days 33 or 57)
- Part 2: Change of Hgb from baseline(Baseline up to Days 33 or 57)
- Part 3: AEs(Up to Days 44)
- Part 3: EPO concentrations(Up to Days 44)
- Part 3: VEGF concentrations(Up to Days 44)
- Part 3: Change of hepcidin from baseline(Up to Days 44)
- Part 3: Change of RTC from baseline(Baseline up to Days 44)
- Part 3: Change of RBC from baseline(Baseline up to Days 44)
- Part 3: Change of Hgb from baseline(Baseline up to Days 44)