Clinical trial NCT04317833: A Study of SSS17 in Healthy Subjects
Official title: A Single Dose Escalation Study to Investigate the Tolerability, Safety, Pharmacokinetics and Pharmacodynamics of SSS17 in Chinese Healthy Subject
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Anemia in Chronic Kidney Diseases
Lead sponsor: Shenyang Sunshine Pharmaceutical Co., LTD.
Sponsor class: INDUSTRY
First posted: 2020-03-23
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human, Phase 1, single-center, randomized, single-blind, placebo-controlled, single dose-escalation study to evaluate the safety, tolerability, PK, PD of SSS17 following oral administration in healthy subjects. Approximately 65 subjects (53 receiving active drug and 12 receiving placebo) will participate in this study.

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 improved Fibonacci dose escalation design will be implemented. The protocol specifies 10 mg, oral, one time for the first cohort without placebo control. Successive cohorts will be given doses up to 540 mg with placebo parallel control. Only no observation meets the criteria under stop rules, dose will escalate to the next higher level.

The study will be divided into 2 stages: 1st period (fast) and 2nd period(fed).

First period (fast): Subjects will be allocated 1:4 to receive placebo or SSS17, which will be administered by oral route. At each dose, tolerability, safety, PK and PD characteristics will be investigated.

Second period (fed): in order to investigate the effects of food on PK and PD of SSS17. Subjects in one cohort will be administered again after meal on Day15. The accurate dose will be adjusted according to the findings in 1st period (fast)

Eligibility criteria: Inclusion Criteria:

* Body weight≥50 for male or ≥45 for female, and BMI between 19.0-26.0 kg/m2
* Good general health as determined by the investigator based on medical history, physical examination, vital signs, 12-lead ECG, clinical laboratory tests and B-type ultrasound test.
* Participants of reproductive potential must agree to utilize reliable methods of contraception from screening to 6 months after the last administration of the study intervention. No plan for sperm (or egg) donation or pregnancy.
* Understand and sign the informed consent.
* Ability to understand and follow study-related instruction

Exclusion Criteria:

* A known allergy to any component of the SSS17 formulation, or allergy history of two kinds of drugs or food
* Medical history or conditions of digestive system.
* Female volunteers who are pregnant, menstrual, lactating or menopause with hormone therapy.
* Eyes diseases, including diabetic retinopathy, age-related macular degeneration.
* Vascular anomalies.
* Drug, alcohol or nicotine addiction.
* Blood donation or bleeding (more than 200 ml). Experience of treatment with EPO or blood transfusion.
* Any findings from the medical examination (including medical history, physical examination, vital signs, laboratory tests and ECG) deviating from normal and deemed by the investigator to be of clinical relevance
* Abnormal results in test of TIBC, serum iron or ferritin
* Acute diseases before administration.
* Other situations that the researcher believes may affect validity judgment or are not suitable for participation

Primary outcomes:
measure: AEs
timeFrame: up to Day14 or 29
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of SSS17
timeFrame: [ up to 48 hours post-dose]
measure: Area under the concentration-time curve (AUC) of plasma concentration of SSS17
timeFrame: [ up to 48 hours post-dose]
measure: Time-to-Cmax (Tmax) of SSS 17
timeFrame: [ up to 48 hours post-dose]
measure: Elimination terminal half-life (t1/2) of SSS17
timeFrame: [up to 48 hours post-dose]
measure: Total amount of SSS17 excreted in urine over 24 hours (Ae0-24)
timeFrame: only for one cohort (up to 72 hours post-dose)
measure: Fraction of SSS17 excretion during each collection interval (Fe0-24)
timeFrame: only for one cohort (up to 72 hours post-dose)
measure: Total amount of SSS17 excreted in urine over 72 hours (Ae0-72)
timeFrame: only for one cohort (up to 72 hours post-dose)
measure: Fraction of SSS17 excretion during each collection interval (Fe0-72)
timeFrame: only for one cohort (up to 72 hours post-dose)
measure: Renal clearance (CLR) of SSS17
timeFrame: only for one cohort (up to 72 hours post-dose)
measure: EPO concentrations
timeFrame: up to 168 hours post-dose.
measure: VEGF concentrations
timeFrame: up to 168 hours post-dose.
measure: Change of RTC from baseline
timeFrame: up to 168 hours post-dose.
measure: Change of RBC from baseline
timeFrame: up to 168 hours post-dose.
measure: Change of Hgb from baseline
timeFrame: up to 168 hours post-dose.
measure: Change of hepcidin from baseline
timeFrame: up to 168 hours post-dose.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
Study officials:
References: