A Phase 1 Study of SSS17 in Healthy Subjects.

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Anemia in Chronic Kidney Diseases
• Intervention / Treatment: Drug: Placebo; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Director Li; Phone Number: 18028886429; Email: 747560265@qq.com
• Study Contact Backup: Name: Professor Fang, Ph.D; Phone Number: 13701165926; Email: fygk7000@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510700
      • Recruiting
      • The Fifth Affiliated Hospital of Guangzhou Medical University
      • Contact: Yi Fang, Ph.D; Phone Number: 13701165926; Email: fygk7000@163.com
      • Contact: Yongmei Li, Ph.D; Phone Number: 13640691018; Email: Liyongmei_gz@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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;
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Single Dose Escalation SSS17; Escalating doses of SSS17, single dose administration	Drug: SSS17; SSS17 is a novel small molecule compound which stimulates erythropoiesis through inhibition of hypoxiainducible factor- prolyl hydroxylases( HIF-PH). It is being developed for the treatment of anemia in patients with chronic kidney disease.
Placebo Comparator: Part 1: Single Dose Escalation matching Placebo; Escalating doses of matching placebo, single dose administration	Drug: Placebo; Matched placebo.
Experimental: Part 2: Multiple Dose Escalation SSS17; Escalating doses of SSS17, multiple dose administration	Drug: SSS17; SSS17 is a novel small molecule compound which stimulates erythropoiesis through inhibition of hypoxiainducible factor- prolyl hydroxylases( HIF-PH). It is being developed for the treatment of anemia in patients with chronic kidney disease.
Placebo Comparator: Part 2: Multiple Dose Escalation matching Placebo; Escalating doses of matching placebo, multiple dose administration	Drug: Placebo; Matched placebo.
Experimental: 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	Drug: SSS17; SSS17 is a novel small molecule compound which stimulates erythropoiesis through inhibition of hypoxiainducible factor- prolyl hydroxylases( HIF-PH). It is being developed for the treatment of anemia in patients with chronic kidney disease.
Experimental: 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	Drug: SSS17; SSS17 is a novel small molecule compound which stimulates erythropoiesis through inhibition of hypoxiainducible factor- prolyl hydroxylases( HIF-PH). It is being developed for the treatment of anemia in patients with chronic kidney disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: AEs	Assessment AEs by frequency and severity in the part 1	Baseline up to Days 15
Part 1: Maximum plasma concentration (Cmax) of SSS17	Plasma samples will be collected and Cmax will be assessed in the part 1	Up to 336 hours post-dose
Part 1: Area under the concentration-time curve (AUC) of plasma concentration of SSS17	Plasma samples will be collected and the AUC from zero to infinity will be assessed in the part 1	Up to 336 hours post-dose
Part 1: Time-to-Cmax (Tmax) of SSS 17	Plasma samples will be collected and the Tmax will be assessed from the concentration-time curve in the part 1	Up to 336 hours post-dose
Part 1: Elimination terminal half-life (t1/2) of SSS17	Plasma samples will be collected and the t1/2 will be assessed in the part 1	Up to 336 hours post-dose
Part 1: . Total amount of SSS17 excreted in urine over 72 hours (Ae0-72)	Urine sample will be collected at pre-specified intervals and Ae0-72 will be assessed in the part 1	Up to 72 hours post-dose
Part 1: Fraction of SSS17 excretion during each collection interval (Fe0-72)	Urine sample will be collected at pre-specified intervals and Fe0-72 will be assessed in the part 1	Up to 72 hours post-dose
Part 1: Renal clearance (CLR) of SSS17	Urine sample will be collected at pre-specified intervals and CLR will be assessed in the part 1	Up to 72 hours post-dose
Part 2: AEs	Assessment AEs by frequency and severity in the part 2	Up to Days 33 or 57
Part 2: Steady state minimal concentration (Css_min) of SSS17	Plasma samples will be collected and Css_min will be assessed in the part 2	Up to Days 33 or 57
Part 2: Steady state maximum concentration (Css_max) of SSS17	Plasma samples will be collected and Css_max will be assessed in the part 2	Up to Days 33 or 57
Part 2: Steady state average concentration (Css_av) of SSS17	Plasma samples will be collected and Css_av will be assessed in the part 2	Up to Days 33 or 57
Part 2: Area under the concentration-time curve of plasma concentration of SSS17 within the interval of administration after reaching steady state (AUC0-τ)	Plasma samples will be collected and the AUC from zero to τ will be assessed	Up to Days 33 or 57
Part 3: Maximum plasma concentration (Cmax) of SSS17	Plasma samples will be collected and Cmax will be assessed in the part 3	Up to Days 44
Part 3: Area under the concentration-time curve (AUC) of plasma concentration of SSS17	Plasma samples will be collected and the AUC from zero to infinity will be assessed in the part 3	Up to Days 44
Part 3: Time-to-Cmax (Tmax) of SSS 17	Plasma samples will be collected and the Tmax will be assessed from the concentration-time curve in the part 3	Up to Days 44
Part 3: Elimination terminal half-life (t1/2) of SSS17	Plasma samples will be collected and the t1/2 will be assessed in the part 3	Up to Days 44

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: EPO concentrations	Change of EPO concentrations from baseline following SSS17 in the part 1	Up to 168 hours post-dose
Part 1: VEGF concentrations	Change of VEGF concentrations from baseline following SSS17 in the part 1	Up to 168 hours post-dose
Part 1: Change of hepcidin from baseline	Change of serum hepcidin concentrations from baseline following SSS17 in the part 1	Up to 168 hours post-dose
Part 1: Change of RTC from baseline	Change of RTC from baseline following SSS17 in the part 1	Baseline up to Days 15
Part 1: Change of RBC from baseline	Change of RBC from baseline following SSS17 in the part 1	Baseline up to Days 15
Part 1: Change of Hgb from baseline	Change of Hgb from baseline following SSS17 in the part 1	Baseline up to Days 15
Part 2: EPO concentrations	Change of EPO concentrations from baseline following SSS17 in the part 2	Up to Days 33 or 57
Part 2: VEGF concentrations	Change of VEGF concentrations from baseline following SSS17 in the part 2	Up to Days 33 or 57
Part 2: Change of hepcidin from baseline	Change of serum hepcidin concentrations from baseline following SSS17 in the part 2	Up to Days 33 or 57
Part 2: Change of RTC from baseline	Change of RTC from baseline following SSS17 in the part 2	Baseline up to Days 33 or 57
Part 2: Change of RBC from baseline	Change of RBC from baseline following SSS17 in the part 2	Baseline up to Days 33 or 57
Part 2: Change of Hgb from baseline	Change of Hgb from baseline following SSS17 in the part 2	Baseline up to Days 33 or 57
Part 3: AEs	Assessment AEs by frequency and severity in the part 3	Up to Days 44
Part 3: EPO concentrations	Change of EPO concentrations from baseline following SSS17 in the part 3	Up to Days 44
Part 3: VEGF concentrations	Change of VEGF concentrations from baseline following SSS17 in the part 3	Up to Days 44
Part 3: Change of hepcidin from baseline	Change of serum hepcidin concentrations from baseline following SSS17 in the part 3	Up to Days 44
Part 3: Change of RTC from baseline	Change of RTC from baseline following SSS17 in the part 3	Baseline up to Days 44
Part 3: Change of RBC from baseline	Change of RBC from baseline following SSS17 in the part 3	Baseline up to Days 44
Part 3: Change of Hgb from baseline	Change of Hgb from baseline following SSS17 in the part 3	Baseline up to Days 44

Collaborators and Investigators

• Sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.
• Collaborators: Fifth Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 19, 2021

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: December 27, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: SYSS-SSS17-UND-I-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No