Study in Chinese Healthy Adults to Evaluate the Safety, Tolerability and Pharmacokinetics on ZSP0678, and the Effect of Food on ZSP0678 Pharmacokinetics

Guangdong Raynovent Biotech

Status and phase: Completed; Phase 1

Conditions: Nonalcoholic Steatohepatitis

Treatments: Drug: ZSP0678; Drug: ZSP0678-120mg; Drug: ZSP0678-240mg; Drug: ZSP0678-180mg; Drug: ZSP0678-Dose 2; Drug: ZSP0678-Dose 3; Drug: ZSP0678-Dose 1; Drug: ZSP0678-30mg; Drug: ZSP0678-320mg; Drug: ZSP0678-10mg; Drug: ZSP0678 Placebo; Drug: ZSP0678-60mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04137055

ZSP0678-19-01

Details and patient eligibility

About

This study will evaluate the safety, tolerability and pharmacokinetics (PK) of escalating single-and multiple-oral doses of ZSP0678 on fasted condition, and characterize PK of ZSP0678 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 ZSP0678 or placebo .

Enrollment: 104 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Subjects are required to meet the following criteria in order to be included in the trial:

  1. Signature signed informed consent before the trial, and fully understood the content, process and possible adverse reactions.

  2. Subjects must be willing and able to complete the research according to the experimental protocol.

  3. Subjects (including partners) are willing to take effective contraceptive measures and have no pregnancy plan during the whole study period until 6 months after drug withdrawal.

  4. Male and female subjects aged 18-50 (including 18 and 50)

  5. Body weight of male subjects should not be less than 50kg and that of female subjects should not be less than 45kg.Body mass index (BMI) = weight (kg)/height 2 (m2), the range of 19~26kg/m2 (including the critical value);

  6. 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.

  7. 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:

  1. Allergic constitution (allergic to many drugs, especially to ingredients similar to the test drug and food)
  2. The average daily smoking are more than 5 cigarettes within 3 months prior to screening.
  3. Known history of drug or alcohol abuse.(defined as consumption of more than 30g of ethanol a day for male and more than 20 g for female )
  4. Subjects who donated blood or bleeding profusely(> 400 mL)in the 3 months preceding study screening.
  5. History of dysphagia or any gastrointestinal illness that affects drug absorption, including a history of frequent nausea or vomiting from any cause, irregular gastrointestinal motility, such as habitual diarrhea, constipation, or irritable bowel syndrome.
  6. History or presence of any disease or condition known to increase the risk of bleeding, eg.acute gastritis, duodenal ulcer, etc.
  7. Participated in another clinical research study and received any investigational products within 3 months prior to dosing.
  8. Use of any prescription or over-the-counter (OTC) medications, vitamins and herbal within 14 days prior to screening.
  9. History of having any special food(including dragon fruit, mango, grapefruit, etc.),strenuous exercises,or other factors may interfere with the absorption, distribution, metabolism, or excretion of drug within 14 days prior to screening.
  10. Subjects who cannot tolerate standard meals (this clause only applies to subjects participating in food impact studies).
  11. Presence of clinically significant abnormalities in ECG or QTcB>450ms in males,or QTcB>470ms in females.
  12. Pregnancy or breastfeeding at screening and during the study.All female subjects of childbearing potential must have a negative urine pregnancy test at screening and during the trial.
  13. Any clinically significant abnormality upon physical examination or in the clinical laboratory tests. History or presence of a clinically significant gastrointestinal, renal, hepatic, neurologic, hematic, endocrine, neoplastic, pulmonary, immune, psychiatric or cardiovascular and cerebrovascular disorder(s) (but not limited to above disorders).
  14. Presence of human immunodeficiency virus (HIV), viral hepatitis(including hepatitis C virus (HCV) or hepatitis B virus (HBV) ),treponema pallidum antibodies at screening.
  15. Any acute illness or concomitant medication from screening to first dosing.
  16. Have chocolate, any food or beverage that contains caffeine ,xanthine and alcohol within 24 hours prior to dosing.
  17. Positive for urine drug screening or history of substance abuse for a period of 5 consecutive years before screening.
  18. As judged by the researcher, it is not suitable to join the clinical researcher.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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104 participants in 11 patient groups

ZSP0678-10mg (single dose)-Cohort 1

Experimental group

Description:

ZSP0678/Placebo 10mg

Treatment:

Drug: ZSP0678-10mg

Drug: ZSP0678 Placebo

ZSP0678-30mg (single dose)-Cohort 2

Experimental group

Description:

ZSP0678/Placebo 30 mg Enrollment into Cohort 2 will begin upon assurance of safety for Cohort 1.

Treatment:

Drug: ZSP0678 Placebo

Drug: ZSP0678-30mg

ZSP0678-60mg (single dose)-Cohort 3

Experimental group

Description:

ZSP0678/Placebo 60mg Enrollment into Cohort 3 will begin upon assurance of safety for Cohort 2.

Treatment:

Drug: ZSP0678 Placebo

Drug: ZSP0678-60mg

ZSP0678-120mg (single dose)-Cohort 4

Experimental group

Description:

ZSP0678/Placebo 120mg Enrollment into Cohort 4 will begin upon assurance of safety for Cohort 3.

Treatment:

Drug: ZSP0678-120mg

Drug: ZSP0678 Placebo

ZSP0678-180mg (single dose)-Cohort 5

Experimental group

Description:

ZSP0678/Placebo 180mg Enrollment into Cohort 5 will begin upon assurance of safety for Cohort 4.

Treatment:

Drug: ZSP0678-180mg

Drug: ZSP0678 Placebo

ZSP0678-240mg (single dose)-Cohort 6

Experimental group

Description:

ZSP0678/Placebo 240mg Enrollment into Cohort 6 will begin upon assurance of safety for Cohort 5.

Treatment:

Drug: ZSP0678-240mg

Drug: ZSP0678 Placebo

ZSP0678-320mg (single dose)-Cohort 7

Experimental group

Description:

ZSP0678/Placebo 320mg Enrollment into Cohort 7 will begin upon assurance of safety for Cohort 6.

Treatment:

Drug: ZSP0678-320mg

Drug: ZSP0678 Placebo

ZSP0678 (food effect)-Cohort FE

Experimental group

Description:

Period 1: Group A and Group B receive ZSP0678/Placebo under the fasting or fed condition ,respectively on Day1. Period 2: Group A and Group B receive ZSP0678/Placebo under the fed or fasting condition ,respectively on Day8. Enrollment into Cohort FE will begin upon assurance of safety for Cohort 4.

Treatment:

Drug: ZSP0678

Drug: ZSP0678 Placebo

ZSP0678 Dose1 (multiple doses)-Cohort 8

Experimental group

Description:

ZSP0678/Placebo Dose1 will be administrated according to the results of Cohort 2\&3

Treatment:

Drug: ZSP0678-Dose 1

Drug: ZSP0678 Placebo

ZSP0678 Dose2 (multiple doses)-Cohort 9

Experimental group

Description:

ZSP0678/Placebo Dose2 will be administrated according to the results of Cohort 3\&4

Treatment:

Drug: ZSP0678-Dose 2

Drug: ZSP0678 Placebo

ZSP0678 Dose3 (multiple doses)-Cohort 10

Experimental group

Description:

ZSP0678/Placebo Dose3 will be administrated according to the results of Cohort 4\&5

Treatment:

Drug: ZSP0678-Dose 3

Drug: ZSP0678 Placebo