Study in Chinese Healthy Adults to Evaluate the Safety, Tolerability and Pharmacokinetics on ZSP1601, and the Effect of Food on ZSP1601 Pharmacokinetics

NCT ID: NCT03392779

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-05
• Study Completion Date: 2019-03-22

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.

Conditions

Nonalcoholic Steatohepatitis (NASH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ZSP1601(single dose)-25 mg while fasted(Cohort 1)

ZSP1601 25 mg /Placebo

Group Type: EXPERIMENTAL

ZSP1601 25 mg

Intervention Type: DRUG

ZSP1601 tablet administered orally once daily under fasted condition

Placebo 25mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

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.

Group Type: EXPERIMENTAL

ZSP1601 50 mg

Intervention Type: DRUG

ZSP1601 tablet administered orally once daily under fasted condition

Placebo 50 mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

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.

Group Type: EXPERIMENTAL

ZSP1601 100 mg

Intervention Type: DRUG

ZSP1601 tablets administered orally once daily in the fasting state

Placebo 100 mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state

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.

Group Type: EXPERIMENTAL

ZSP1601 175 mg

Intervention Type: DRUG

ZSP1601 tablets administerekd orally once daily under fasted condition

Placebo 175 mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

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.

Group Type: EXPERIMENTAL

ZSP1601 275 mg

Intervention Type: DRUG

ZSP1601 tablets administered orally once daily in the fasting state

Placebo 275 mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state

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.

Group Type: EXPERIMENTAL

ZSP1601 350 mg

Intervention Type: DRUG

ZSP1601 tablets administered orally once daily under fasted condition

Placebo 350mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

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.

Group Type: EXPERIMENTAL

ZSP1601 100 mg

Intervention Type: DRUG

ZSP1601 tablets administered orally once daily under fasted or fed condition

Placebo 100mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition

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.

Group Type: EXPERIMENTAL

ZSP1601 50 mg

Intervention Type: DRUG

ZSP1601 tablets administered orally once daily under fasted or fed condition due to the results of Cohort FE for 14 Days(a total of 14 doses).

Placebo 50 mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition due to the results of Cohort FE for 14 Days(a total of 14 doses).

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.

Group Type: EXPERIMENTAL

ZSP1601 100 mg

Intervention Type: DRUG

ZSP1601 tablets administered orally once daily under fasted or fed condition due to the results of Cohort FE for 14 Days(a total of 14 doses).

Placebo 100 mg

Intervention Type: DRUG

Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition due to the results of Cohort FE for 14 Days(a total of 14 doses).

Interventions

ZSP1601 25 mg

ZSP1601 tablet administered orally once daily under fasted condition

Intervention Type: DRUG

Placebo 25mg

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

Intervention Type: DRUG

ZSP1601 50 mg

ZSP1601 tablet administered orally once daily under fasted condition

Intervention Type: DRUG

Placebo 50 mg

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

Intervention Type: DRUG

ZSP1601 100 mg

ZSP1601 tablets administered orally once daily in the fasting state

Intervention Type: DRUG

Placebo 100 mg

Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state

Intervention Type: DRUG

ZSP1601 175 mg

ZSP1601 tablets administerekd orally once daily under fasted condition

Intervention Type: DRUG

Placebo 175 mg

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

Intervention Type: DRUG

ZSP1601 275 mg

ZSP1601 tablets administered orally once daily in the fasting state

Intervention Type: DRUG

Placebo 275 mg

Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state

Intervention Type: DRUG

ZSP1601 350 mg

ZSP1601 tablets administered orally once daily under fasted condition

Intervention Type: DRUG

Placebo 350mg

Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition

Intervention Type: DRUG

ZSP1601 100 mg

ZSP1601 tablets administered orally once daily under fasted or fed condition

Intervention Type: DRUG

Placebo 100mg

Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition

Intervention Type: DRUG

ZSP1601 50 mg

ZSP1601 tablets administered orally once daily under fasted or fed condition due to the results of Cohort FE for 14 Days(a total of 14 doses).

Intervention Type: DRUG

Placebo 50 mg

Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition due to the results of Cohort FE for 14 Days(a total of 14 doses).

Intervention Type: DRUG

ZSP1601 100 mg

ZSP1601 tablets administered orally once daily under fasted or fed condition due to the results of Cohort FE for 14 Days(a total of 14 doses).

Intervention Type: DRUG

Placebo 100 mg

Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition due to the results of Cohort FE for 14 Days(a total of 14 doses).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

1. 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.

2. Subjects must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study.

3. 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.

4. Males and female subjects between 18-50 years (Both inclusive).

5. 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).

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

1. The average daily smoking are more than 5 cigarettes within 3 months prior to screening.

2. Known hypersensitivity and/or allergy to some drugs and food.

3. 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 )

4. Subjects who donated blood or bleeding profusely(> 400 mL)in the 3 months preceding study screening.

5. Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs.

6. History or presence of any disease or condition known to increase the risk of bleeding, eg.acute gastritis, duodenal ulcer, etc.

7. Frequently suffers from postural hypotension.

8. History of frequent nausea or vomit causes by any etiology.

9. 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.

10. Use of any prescription or over-the-counter (OTC) medications, vitamins and herbal or dietary supplements within 14 days prior to screening.

11. 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.

12. Subjects with recent significant change in diet or exercise .

13. Participated in another clinical research study and received any investigational products within 3 months prior to dosing.

14. Inability to consume the food provided in the study ( a high fat, high calorie meal includes two eggs for 100g, bacon 20g, a butter toast for 50g, french fries for 115g, whole milk for 240ml).This requirement only applies to subjects under fed condition.

15. Presence of clinically significant abnormalities in ECG or QTc>470ms in males,or QTc>480ms in females.

16. 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.

17. 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).

18. Presence of human immunodeficiency virus (HIV), viral hepatitis(including hepatitis C virus (HCV) or hepatitis B virus (HBV) ),treponema pallidum antibodies at screening.

19. Any acute illness or concomitant medication from screening to first dosing.

20. Have chocolate, any food or beverage that contains caffeine or xanthine within 24 hours prior to dosing.

21. Take any product contains alcohol within 24 hours prior to dosing.

22. Positive for urine drug screening or history of substance abuse for a period of 5 consecutive years before screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Guangdong Zhongsheng Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yanhua Ding, MD

Role: PRINCIPAL_INVESTIGATOR

The First Hospital of Jilin University

Locations

The First Hospital of Jilin University

Changchun, Jilin, China

Countries

China

References

Zhu X, Wu M, Wang H, Li H, Lin J, Peng Y, Hu Y, Li C, Ding Y. Safety, tolerability, and pharmacokinetics of the novel pan-phosphodiesterase inhibitor ZSP1601 in healthy subjects: a double-blinded, placebo-controlled first-in-human single-dose and multiple-dose escalation and food effect study. Expert Opin Investig Drugs. 2021 May;30(5):579-589. doi: 10.1080/13543784.2021.1900822. Epub 2021 Mar 25.

Reference Type: DERIVED

PMID: 33682556 (View on PubMed)

Other Identifiers

ZSP1601-16-01

Identifier Type: -

Identifier Source: org_study_id