A Phase 1 Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ZSP1273 and the Effect of Food on ZSP1273 Pharmacokinetics in Chinese Healthy Subjects.
Overview
- Phase
- Phase 1
- Intervention
- Placebo 1200 mg
- Conditions
- Influenza
- Sponsor
- Guangdong Zhongsheng Pharmaceutical Co., Ltd.
- Enrollment
- 103
- Locations
- 1
- Primary Endpoint
- Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a single center,double-blind,randomized,parallel design, single and multiple dose trial to evaluate the pharmacokinetics(PK), safety and tolerability of ZSP1273,and the effect of food on ZSP1273 Pharmacokinetics.
Detailed Description
The study will be divided in 3 parts : Study Part I(Single Ascending Dosing, SAD) will be a single ascending dose to be run at a maximum of 6 dose levels. Subjects included in this part of the study will receive only one dose level to limit the exposure to ZSP1273. Four subjects are planned to be included in the first group while 10 subjects are enrolled in every following cohort. Study Part II(Multiple Ascending Dosing, MAD) will start after completion of some Cohorts of Study Part I. Study Part II will be a multiple ascending dose to be run at a maximum of 3 dose levels. Subjects included in this part of the study will receive only one dose level. This part also enrolls 10 subjects in every cohort. Study Part III(Food Effect study, FE) will consists of 2 periods,and subjects will receive a single dose ranged from 100-600mg on fasting and postprandial states respectively. There will be a 7-day wash out period between treatment periods.A total of 12 to 18 subjects will be included. All the 3 parts will be run in healthy subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects are required to meet the following criteria in order to be included in the trial:
- •Signature of a dated Informed Consent Form (ICF) indicating that the subject has been informed of all the relevant aspects(including adverse events) of the trial prior to enrollment.
- •Subjects must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study.
- •Subjects (including partners) must use reliable methods of contraception during the study and until 6 months following the last dose of investigational product.
- •Males and female subjects between 18-50 years (Both inclusive).
- •Body weight is no less than 50 kg in males and no less than 45 kg in females. Body mass index (BMI) 18≤BMI≤28 kg/m2; BMI is determined by the following equation: BMI = weight/height2 (kg/m2).
- •Physical condition and vital signs: Normal or abnormality has no clinical significance.
Exclusion Criteria
- •Eligible subjects must not meet any of the following exclusion criteria:
- •Known hypersensitivity and/or allergy to some drugs and food, especially for the composition that is similar to the investigative product;
- •The average daily smoking are more than 5 cigarettes within 3 months prior to screening.
- •Known history of drug or alcohol abuse.(defined as consumption of 14 units of alcohol per week: 1 unit = 285 ml of beer; or the equivalent of 25 ml of spirit, or 100 ml of wine )
- •Subjects who donated blood or bleeding profusely (\> 400 mL) in the 3 months preceding study screening.
- •Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs, include a history of frequent nausea or vomit causes by any etiology.
- •History or presence of any disease or condition known to increase the risk of bleeding , eg. acute gastritis, duodenal ulcer, etc.
- •Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, or urticaria.
- •Subjects with recent significant change in diet or exercise.
- •Participated in another clinical research study and received any investigational products within 3 months prior to dosing.
Arms & Interventions
ZSP1273(single dose)-1200 mg(Cohort 6)
ZSP1273 1200 mg/Placebo Enrollment into Cohort 6 will begin upon assurance of tolerance for Cohort 5.
Intervention: Placebo 1200 mg
ZSP1273(single dose)-1200 mg(Cohort 6)
ZSP1273 1200 mg/Placebo Enrollment into Cohort 6 will begin upon assurance of tolerance for Cohort 5.
Intervention: ZSP1273 1200 mg
ZSP1273(single dose)-100 mg(Cohort 1)
ZSP1273 100 mg /Placebo
Intervention: ZSP1273 100 mg
ZSP1273(single dose)-100 mg(Cohort 1)
ZSP1273 100 mg /Placebo
Intervention: Placebo 100 mg
ZSP1273(single dose)-200 mg(Cohort 2)
ZSP1273 200mg/Placebo Enrollment into Cohort 2 will begin upon assurance of tolerance for Cohort 1.
Intervention: ZSP1273 200 mg
ZSP1273(single dose)-200 mg(Cohort 2)
ZSP1273 200mg/Placebo Enrollment into Cohort 2 will begin upon assurance of tolerance for Cohort 1.
Intervention: Placebo 200 mg
ZSP1273(single dose)-400 mg(Cohort 3)
ZSP1273 400mg/Placebo Enrollment into Cohort 3 will begin upon assurance of tolerance for Cohort 2.
Intervention: ZSP1273 400 mg
ZSP1273(single dose)-400 mg(Cohort 3)
ZSP1273 400mg/Placebo Enrollment into Cohort 3 will begin upon assurance of tolerance for Cohort 2.
Intervention: Placebo 400 mg
ZSP1273(single dose)-600 mg(Cohort 4)
ZSP1273 600 mg/Placebo Enrollment into Cohort 4 will begin upon assurance of tolerance for Cohort 3.
Intervention: ZSP1273 600 mg
ZSP1273(single dose)-600 mg(Cohort 4)
ZSP1273 600 mg/Placebo Enrollment into Cohort 4 will begin upon assurance of tolerance for Cohort 3.
Intervention: Placebo 600 mg
ZSP1273(single dose)-900 mg(Cohort 5)
Drug:ZSP1273 900 mg/Placebo 900mg； Enrollment into Cohort 5 will begin upon assurance of tolerance for Cohort 4.
Intervention: ZSP1273 900 mg
ZSP1273(single dose)-900 mg(Cohort 5)
Drug:ZSP1273 900 mg/Placebo 900mg； Enrollment into Cohort 5 will begin upon assurance of tolerance for Cohort 4.
Intervention: Placebo 900 mg
ZSP1273(Food Effect)-Cohort 7
Drug:ZSP1273 /Placebo； Period 1 (Day1 to Day5): Subjects receive ZSP1273/Placebo under the fasting or fed condition ,respectively on Day1. Period 2 (Day 8 to Day12): Subjects receive ZSP1273/Placebo under the fed or fasting condition, respectively on Day 8.
Intervention: ZSP1273
ZSP1273(Food Effect)-Cohort 7
Drug:ZSP1273 /Placebo； Period 1 (Day1 to Day5): Subjects receive ZSP1273/Placebo under the fasting or fed condition ,respectively on Day1. Period 2 (Day 8 to Day12): Subjects receive ZSP1273/Placebo under the fed or fasting condition, respectively on Day 8.
Intervention: Placebo
ZSP1273(multiple doses)-Low Dose(Cohort 8)
while fasted or fed according to the results of Cohort FE ZSP1273 /Placebo for 5 Days.
Intervention: ZSP1273 Low Dose
ZSP1273(multiple doses)-Low Dose(Cohort 8)
while fasted or fed according to the results of Cohort FE ZSP1273 /Placebo for 5 Days.
Intervention: Placebo
ZSP1273(multiple doses)-Median Dose(Cohort 9)
while fasted or fed according to the results of Cohort FE ZSP1273/Placebo for 5 Days.
Intervention: ZSP1273 Median Dose
ZSP1273(multiple doses)-Median Dose(Cohort 9)
while fasted or fed according to the results of Cohort FE ZSP1273/Placebo for 5 Days.
Intervention: Placebo
ZSP1273(multiple doses)-High Dose(Cohort 10)
while fasted or fed according to the results of Cohort FE ZSP1273/Placebo for 5 Days.
Intervention: ZSP1273 High Dose
ZSP1273(multiple doses)-High Dose(Cohort 10)
while fasted or fed according to the results of Cohort FE ZSP1273/Placebo for 5 Days.
Intervention: Placebo
Outcomes
Primary Outcomes
Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE)
Time Frame: At day 5, 9, 12 days post first dosing for SAD, MAD, FE part respectively
Number of participants with TEAEs as assessed by CTCAE v5.0.
Secondary Outcomes
- Cmax(UP to 5, 9, 12 days for SAD, MAD, FE part respectively)
- CL/F(UP to 5, 9, 12 days for SAD, MAD, FE part respectively)
- Tmax(UP to 5, 9, 12 days for SAD, MAD, FE part respectively)
- AUClast（AUC0-t）(UP to 5, 9, 12 days for SAD, MAD, FE part respectively)
- Food Effect PK Parameter: Fe0-t(UP to 12 days)
- Multiple-dose plasma PK parameter: DF of ZSP1273 at steady state(Up to 9 days)
- Multiple-dose plasma PK parameter: Rac of ZSP1273 at steady state(Up to 9 days)
- t1/2z(UP to 5, 9, 12 days for SAD, MAD, FE part respectively)
- AUCinf（AUC0-∞）(UP to 5, 9, 12 days for SAD, MAD, FE part respectively)
- λz(UP to 5, 9, 12 days for SAD, MAD, FE part respectively)
- CLr(UP to 5, 9, 12 days for SAD, MAD, FE part respectively)
- Food Effect PK Parameter: Ae(UP to 12 days)
- Multiple-dose plasma PK parameter: Cmin of ZSP1273 at steady state(Up to 9 days)