A Phase 1 Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ZSP1601 and the Effect of Food on ZSP1601 Pharmacokinetics in Chinese Healthy Subjects.
Overview
- Phase
- Phase 1
- Intervention
- ZSP1601 25 mg
- Conditions
- Nonalcoholic Steatohepatitis (NASH)
- Sponsor
- Guangdong Zhongsheng Pharmaceutical Co., Ltd.
- Enrollment
- 94
- Locations
- 1
- Primary Endpoint
- Concomitant Medication
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This study will evaluate the safety, tolerability and pharmacokinetics (PK) of escalating single- and multiple-oral doses of ZSP1601 on fasted condition, and characterize PK of ZSP1601 on an empty stomach (fasted condition) and following a high fat, high calorie meal (fed condition) in a 2-period, 2-sequence manner. The study will be conducted in 3 parts (Ascending single dose, multiple dose and food effect). Participants will receive either ZSP1601 or placebo .
Detailed Description
The study is a randomized, double-blind phase 1 trial including 3 parts: single ascending dose(SAD) part,multiple ascending dose(MAD) part and postprandial pharmacokinetics part.The primary aims of the study as below: Evaluating the safety and tolerance of single and multiple dose of ZSP1601 in healthy volunteers. Evaluating the fasting and postprandial pharmacokinetic parameters of ZSP1601 in healthy volunteers. Eligible participants will be admitted to the trial center on Day -1. Subjects will be randomly assigned to either experimental groups or placebo groups, according to a randomisation schedule in a (4:1) ratio (8 in per experimental group). Subjects in SAD will receive 25、50、100、175、275、350 mg once daily respectively.Each dose will be administrated after assurance of safety for the former dose. Subjects in MAD will receive 50 or 100 mg once daily for 14days respectively.The treatment in food effect consists of 2 periods,and subjects will receive 100mg on fasting and postprandial states respectively. There will be a 7-day wash out period between treatment periods.To monitor AEs,record abnormalities (12-lead ECG,Vital signs,Physical examination,Clinical Laboratory),and detect the pharmacokinetics of ZSP1601.
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)have no gestation plans and 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 50kg in males and no less than 45kg 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:No significant abnormalities in medical history, including cardiovascular system, liver, kidneys, gastrointestinal system, neural system, respiratory system (eg.asthma,asthma induced by exercise,chronic obstructive pulmonary disease), mental, metabolism, etc.
- •Subjects in general good health or No significant abnormalities in the opinion of the investigator as determined by vital signs and a physical examination.
Exclusion Criteria
- •Eligible subjects must not meet any of the following exclusion criteria:
- •The average daily smoking are more than 5 cigarettes within 3 months prior to screening.
- •Known hypersensitivity and/or allergy to some drugs and food.
- •Known history of drug or alcohol abuse.(defined as consumption of 14 units of alcohol per week:1 unit=285ml of beer; or the equivalent of 25ml of spirit, or 100ml 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.
- •History or presence of any disease or condition known to increase the risk of bleeding, eg.acute gastritis, duodenal ulcer, etc.
- •Frequently suffers from postural hypotension.
- •History of frequent nausea or vomit causes by any etiology.
- •Concomitant therapy with any drugs with known hepatic enzyme-inducing or inhibiting agents that may change the activity of CYP3A4 prior to screening or during the study.
Arms & Interventions
ZSP1601(single dose)-25 mg while fasted(Cohort 1)
ZSP1601 25 mg /Placebo
Intervention: ZSP1601 25 mg
ZSP1601(single dose)-25 mg while fasted(Cohort 1)
ZSP1601 25 mg /Placebo
Intervention: Placebo 25mg
ZSP1601(single dose)-50 mg while fasted(Cohort 2)
ZSP1601 50 mg/Placebo Enrollment into Cohort 2 will begin upon assurance of safety for Cohort 1.
Intervention: ZSP1601 50 mg
ZSP1601(single dose)-50 mg while fasted(Cohort 2)
ZSP1601 50 mg/Placebo Enrollment into Cohort 2 will begin upon assurance of safety for Cohort 1.
Intervention: Placebo 50 mg
ZSP1601(single dose)-100 mg while fasted(Cohort 3)
ZSP1601 100 mg/Placebo Enrollment into Cohort 3 will begin upon assurance of safety for Cohort 2.
Intervention: ZSP1601 100 mg
ZSP1601(single dose)-100 mg while fasted(Cohort 3)
ZSP1601 100 mg/Placebo Enrollment into Cohort 3 will begin upon assurance of safety for Cohort 2.
Intervention: Placebo 100 mg
ZSP1601(single dose)-175 mg while fasted(Cohort 4)
ZSP1601 175 mg/Placebo Enrollment into Cohort 4 will begin upon assurance of safety for Cohort 3.
Intervention: ZSP1601 175 mg
ZSP1601(single dose)-175 mg while fasted(Cohort 4)
ZSP1601 175 mg/Placebo Enrollment into Cohort 4 will begin upon assurance of safety for Cohort 3.
Intervention: Placebo 175 mg
ZSP1601(single dose)-275 mg while fasted(Cohort 5,i.e.Group A)
ZSP1601 275 mg/Placebo Enrollment into Cohort 5 will begin upon assurance of safety for Cohort 4.
Intervention: ZSP1601 275 mg
ZSP1601(single dose)-275 mg while fasted(Cohort 5,i.e.Group A)
ZSP1601 275 mg/Placebo Enrollment into Cohort 5 will begin upon assurance of safety for Cohort 4.
Intervention: Placebo 275 mg
ZSP1601(single dose)-350 mg while fasted(Cohort 6)
ZSP1601 350 mg/Placebo Enrollment into Cohort 6 will begin upon assurance of safety for Cohort 5.
Intervention: ZSP1601 350 mg
ZSP1601(single dose)-350 mg while fasted(Cohort 6)
ZSP1601 350 mg/Placebo Enrollment into Cohort 6 will begin upon assurance of safety for Cohort 5.
Intervention: Placebo 350mg
ZSP1601(food effect)-100 mg (Cohort FE)
Period 1 (Day1 to Day4): Group A and Group B receive ZSP1601 100 mg/Placebo under the fasting or fed condition ,respectively on Day1. Period 2 (Day 8 to Day11): Group A and Group B receive ZSP1601 100 mg/Placebo under the fed or fasting condition ,respectively on Day8.
Intervention: ZSP1601 100 mg
ZSP1601(multiple doses)-100 mg (Cohort 8)
Enrollment into Cohort 8 will begin upon assurance of safety for Cohort 7. ZSP1601 100 mg/Placebo for 14 Days.
Intervention: ZSP1601 100 mg
ZSP1601(food effect)-100 mg (Cohort FE)
Period 1 (Day1 to Day4): Group A and Group B receive ZSP1601 100 mg/Placebo under the fasting or fed condition ,respectively on Day1. Period 2 (Day 8 to Day11): Group A and Group B receive ZSP1601 100 mg/Placebo under the fed or fasting condition ,respectively on Day8.
Intervention: Placebo 100mg
ZSP1601(multiple doses)-50 mg (Cohort 7)
50 mg ZSP1601 will be administrated while fasted or fed according to the results of Cohort FE ZSP1601 50 mg/Placebo for 14 Days.
Intervention: ZSP1601 50 mg
ZSP1601(multiple doses)-50 mg (Cohort 7)
50 mg ZSP1601 will be administrated while fasted or fed according to the results of Cohort FE ZSP1601 50 mg/Placebo for 14 Days.
Intervention: Placebo 50 mg
ZSP1601(multiple doses)-100 mg (Cohort 8)
Enrollment into Cohort 8 will begin upon assurance of safety for Cohort 7. ZSP1601 100 mg/Placebo for 14 Days.
Intervention: Placebo 100 mg
Outcomes
Primary Outcomes
Concomitant Medication
Time Frame: UP to 4, 17, 11 days for SAD, MAD, FE part respectively
Clinical Laboratory Abnormalities(Blood routine test, serum biochemical test, conventional coagulation examinations, urine examination ) post dose of ZSP1601 and placebo.
Time Frame: UP to 4, 17, 11 days for SAD, MAD, FE part respectively
12-lead ECG Abnormalities following oral dosing of ZSP1601 and placebo.
Time Frame: UP to 4, 17, 11 days for SAD, MAD, FE part respectively
Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE) following oral doses(single,multiple and food effect)of ZSP1601 and placebo.
Time Frame: SAD Group: Up to 4 days, MAD: Up to 17days, FE group: Up to 11 days after first dose
Vital signs Abnormalities following oral dosing of ZSP1601 and placebo.
Time Frame: UP to 4, 17, 11 days for SAD, MAD, FE part respectively
Physical examination Abnormalities following oral dossing of ZSP1601 and placebo.
Time Frame: UP to 4, 17, 11 days for SAD, MAD, FE part respectively
Cardiac color ultrasound(UCG) Abnormalities following multiple oral doses of ZSP1601 and placebo.
Time Frame: Screening, Day17
Secondary Outcomes
- AUClast（AUC0-t）of ZSP1601(UP to 2, 16, 9 days for SAD, MAD, FE part respectively)
- AUCinf（AUC0-∞）of ZSP1601(UP to 2, 16, 9 days for SAD, MAD, FE part respectively)
- Cmax of ZSP1601(UP to 2, 16, 9 days for SAD, MAD, FE part respectively)
- Tmax of ZSP1601(UP to 2, 16, 9 days for SAD, MAD, FE part respectively)
- t1/2z of ZSP1601(UP to 2, 16, 9 days for SAD, MAD, FE part respectively)
- Multiple-dose plasma PK parameter: Cmin of ZSP1601 at steady state(Up to 16days)
- Single-dose PK Parameter: Ae of ZSP1601(Up to Day 2 post-dose)
- Single-dose PK Parameter: Fe0-t of ZSP1601(Up to Day 2 post-dose)
- CL/F of ZSP1601(UP to 2, 16, 9 days for SAD, MAD, FE part respectively)
- λz of ZSP1601(UP to 2, 16, 9 days for SAD, MAD, FE part respectively)
- CLr of ZSP1601(UP to 2, 16, 9 days for SAD, MAD, FE part respectively)
- Multiple-dose plasma PK parameter: Rac of ZSP1601 at steady state(Up to 16days)
- Multiple-dose plasma PK parameter: DF of ZSP1601 at steady state(Up to 16 days)