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.
Overview
- Phase
- Phase 1
- Intervention
- SSS17
- Conditions
- Anemia in Chronic Kidney Diseases
- Sponsor
- Shenyang Sunshine Pharmaceutical Co., LTD.
- Enrollment
- 76
- Locations
- 1
- Primary Endpoint
- Part 1: Maximum plasma concentration (Cmax) of SSS17
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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;
Arms & Interventions
Part 1: Single Dose Escalation SSS17
Escalating doses of SSS17, single dose administration
Intervention: SSS17
Part 1: Single Dose Escalation matching Placebo
Escalating doses of matching placebo, single dose administration
Intervention: Placebo
Part 2: Multiple Dose Escalation SSS17
Escalating doses of SSS17, multiple dose administration
Intervention: SSS17
Part 2: Multiple Dose Escalation matching Placebo
Escalating doses of matching placebo, multiple dose administration
Intervention: Placebo
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
Intervention: SSS17
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
Intervention: SSS17
Outcomes
Primary Outcomes
Part 1: Maximum plasma concentration (Cmax) of SSS17
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: Up to Days 44
Plasma samples will be collected and the t1/2 will be assessed in the part 3
Secondary Outcomes
- 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)