Clinical trial NCT03255993: The Tolerability and Pharmacokinetics of Multiple Doses of SPH3127 in Chinese Healthy People
Official title: Multiple Doses Study to Evaluate the Tolerability and Pharmacokinetics of SPH3127 in Chinese Healthy People
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
Sponsor class: INDUSTRY
First posted: 2017-08-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was a single center, parallel, randomized, double blind, placebo-controlled phase Ib clinical trial to to evaluate the safety and tolerability and pharmacokinetics of SPH3127 tablet in healthy subjects by increasing multiple dosing

Detailed description: Three panels(100mg, 200mg, 400mg), each consisting of eight participants (The number of individual subjects in each group was not less than 1/3 of the total number).Participants begin to receive the first dose of SPH3127 100mg. Then Participants begin to receive the second dose of SPH3127 200mg,after the researchers confirmed that the 100mg dose group was safe and well tolerated.Then the third dose of SPH3127 400mg must wait for the result of the second dose's safety and tolerability. If the subjects during escalating dose to the biggest tolerate dose group were not well tolerated, the study must adjust the maximum dose group and fall to a low dose group to conduct another test.

Eligibility criteria: Inclusion Criteria:

1. The body mass index is 18-28kg/m2 (including the critical value), which allows the minimum weight of men to be 50kg (including the critical value) and 45kg for women (including the critical value).
2. Before the study,participant has know about the significance , potential benefits, inconveniences and potential risks of the study
3. Participant has understood the research's procedure and sign the informed consent .

Exclusion Criteria:

* Participant who are Pregnancy, lactating women, and planned trials begin within six months of pregnancy
* Participant who has abnormal Physical examination, laboratory examination results and clinical significance (such as: liver function examination - aspartate aminotransferase (AST) and alanine aminotransferase (ALT) more than 1.5 times that of the upper limit of normal)
* Participant who has a history of cardiovascular, liver, kidney, digestive tract, nervous system, blood system, familial hematologic disease, abnormal thyroid function, or mental abnormality
* Participant who has drug allergy history and anaphylactic reaction
* Participant who took oral contraceptive in 6 months
* Participant who used any drug (including Chinese herbal medicine) within 1 week.
* Participant who donated blood within 2 months
* Participant who participated clinical trials of any drug in 3 months (as subjects)
* Participant who has any positive result of virus serology check: human immunodeficiency virus antigen antibody (HIV Ag/Ab) and hepatitis c virus (HCV) - immunoglobulin G(IgG) antibody to IgG, hepatitis b surface antigen (HBsAg) and treponema pallidum antibody (TP)
* Participant who are used to smoke, alcohol abuse, eat coffee and strong tea and drug abuse
* Participant who the researchers believe that there are volunteers who are not suitable for the study

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Baseline to 13-16 days post last dose
Secondary outcomes:
measure: Plasma area under curve (AUC)(0-∞) of SPH3127
timeFrame: 10 minutes predose, 0.17hour, 0.33hour, 0.5hour, 0.75hour, 1hour, 1.25hour, 1.5hour, 2hour, 4hour, 6hour, 8hour, 12hour postdose at Day 1 and 7; 10 minutes predose at Day 2; 10 minutes predose, 1hour postdose at Day 5 or 6
measure: Change from baseline in laboratory hematology values
timeFrame: Baseline to 13-16 days post last dose
measure: Change from baseline in laboratory chemistry values
timeFrame: Baseline to 13-16 days post last dose
measure: Change from baseline in laboratory urinalysis values
timeFrame: Baseline to 13-16 days post last dose
measure: Change from baseline in ECG
timeFrame: Baseline to 13-16 days post last dose
measure: Maximum Plasma Concentration (Cmax) of SPH3127
timeFrame: 10 minutes predose, 0.17hour, 0.33hour, 0.5hour, 0.75hour, 1hour, 1.25hour, 1.5hour, 2hour, 4hour, 6hour, 8hour, 12hour postdose at Day 1 and 7;10 minutes predose at Day 2; 10 minutes predose, 1hour postdose at Day 5 or 6
measure: Plasma Maximum time to peak (Tmax) of SPH3127
timeFrame: 10 minutes predose, 0.17hour, 0.33hour, 0.5hour, 0.75hour, 1hour, 1.25hour, 1.5hour, 2hour, 4hour, 6hour, 8hour, 12hour postdose at Day 1 and 7;10 minutes predose at Day 2; 10 minutes predose, 1hour postdose at Day 5 or 6
measure: Apparent terminal half-life of SPH3127
timeFrame: 10 minutes predose, 0.17hour, 0.33hour, 0.5hour, 0.75hour, 1hour, 1.25hour, 1.5hour, 2hour, 4hour, 6hour, 8hour, 12hour postdose at Day 1 and 7;10 minutes predose at Day 2; 10 minutes predose, 1hour postdose at Day 5 or 6
Other outcomes:
Locations:
city: Beijing
country: China
facility: The capital medical university affiliated Beijing anzhen hospital
state: Beijing
Study officials:
References:
citation: Jing S, Xu R, Yang K, Liu W, Zhang L, Ke Y, Xia G, Lin Y. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SPH3127: A Phase I, Randomized, Double-Blind, Placebo-Controlled Trial. Clin Ther. 2021 Apr;43(4):735.e1-735.e14. doi: 10.1016/j.clinthera.2021.01.025. Epub 2021 Feb 27.