A Phase 1 Study of SSS17 in Healthy Subjects.
- Conditions
- Anemia in Chronic Kidney Diseases
- Interventions
- Drug: PlaceboDrug: SSS17
- Registration Number
- NCT04893187
- Lead Sponsor
- Shenyang Sunshine Pharmaceutical Co., LTD.
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 76
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Single Dose Escalation matching Placebo Placebo Escalating doses of matching placebo, single dose administration Part 1: Single Dose Escalation SSS17 SSS17 Escalating doses of SSS17, single dose administration Part 2: Multiple Dose Escalation SSS17 SSS17 Escalating doses of SSS17, multiple dose administration Part 3: Treatment Sequence 1 (A to B) SSS17 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 Part 2: Multiple Dose Escalation matching Placebo Placebo Escalating doses of matching placebo, multiple dose administration Part 3: Treatment Sequence 2 (B to A) SSS17 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
- Primary Outcome Measures
Name Time Method Part 1: Maximum plasma concentration (Cmax) of SSS17 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 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 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 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) 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 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) 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 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 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 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 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 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) 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 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 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 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 Up to Days 44 Plasma samples will be collected and the t1/2 will be assessed in the part 3
- Secondary Outcome Measures
Name Time Method Part 1: EPO concentrations Up to 168 hours post-dose Change of EPO concentrations from baseline following SSS17 in the part 1
Part 1: VEGF concentrations Up to 168 hours post-dose Change of VEGF concentrations from baseline following SSS17 in the part 1
Part 3: AEs Up to Days 44 Assessment AEs by frequency and severity in the part 3
Part 1: Change of hepcidin from baseline Up to 168 hours post-dose Change of serum hepcidin concentrations from baseline following SSS17 in the part 1
Part 1: Change of RTC from baseline Baseline up to Days 15 Change of RTC from baseline following SSS17 in the part 1
Part 1: Change of RBC from baseline Baseline up to Days 15 Change of RBC from baseline following SSS17 in the part 1
Part 1: Change of Hgb from baseline Baseline up to Days 15 Change of Hgb from baseline following SSS17 in the part 1
Part 2: EPO concentrations Up to Days 33 or 57 Change of EPO concentrations from baseline following SSS17 in the part 2
Part 2: VEGF concentrations Up to Days 33 or 57 Change of VEGF concentrations from baseline following SSS17 in the part 2
Part 2: Change of hepcidin from baseline Up to Days 33 or 57 Change of serum hepcidin concentrations from baseline following SSS17 in the part 2
Part 2: Change of RTC from baseline Baseline up to Days 33 or 57 Change of RTC from baseline following SSS17 in the part 2
Part 2: Change of RBC from baseline Baseline up to Days 33 or 57 Change of RBC from baseline following SSS17 in the part 2
Part 2: Change of Hgb from baseline Baseline up to Days 33 or 57 Change of Hgb from baseline following SSS17 in the part 2
Part 3: EPO concentrations Up to Days 44 Change of EPO concentrations from baseline following SSS17 in the part 3
Part 3: VEGF concentrations Up to Days 44 Change of VEGF concentrations from baseline following SSS17 in the part 3
Part 3: Change of hepcidin from baseline Up to Days 44 Change of serum hepcidin concentrations from baseline following SSS17 in the part 3
Part 3: Change of RTC from baseline Baseline up to Days 44 Change of RTC from baseline following SSS17 in the part 3
Part 3: Change of RBC from baseline Baseline up to Days 44 Change of RBC from baseline following SSS17 in the part 3
Part 3: Change of Hgb from baseline Baseline up to Days 44 Change of Hgb from baseline following SSS17 in the part 3
Trial Locations
- Locations (1)
The Fifth Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China