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

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ClinicalTrials.gov Identifier: NCT03392779
Recruitment Status : Recruiting
First Posted : January 8, 2018
Last Update Posted : August 2, 2018
Sponsor:
Information provided by (Responsible Party):
Guangdong Zhongsheng Pharmaceutical Co., Ltd.

Tracking Information
First Submitted Date  ICMJE January 2, 2018
First Posted Date  ICMJE January 8, 2018
Last Update Posted Date August 2, 2018
Actual Study Start Date  ICMJE January 5, 2018
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
  • 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 ]
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
  • 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 10days, FE group: Up to 11 days after first dose ]
  • Concomitant Medication [ Time Frame: UP to 4, 10, 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, 10, 11 days for SAD, MAD, FE part respectively ]
  • 12-lead ECG Abnormalities following oral dosing of ZSP1601 and placebo. [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
  • Vital signs Abnormalities following oral dosing of ZSP1601 and placebo. [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
  • Physical examination Abnormalities following oral dossing of ZSP1601 and placebo. [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
  • Cardiac color ultrasound(UCG) Abnormalities following multiple oral doses of ZSP1601 and placebo. [ Time Frame: Screening, Day10 ]
Change History Complete list of historical versions of study NCT03392779 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
  • AUClast(AUC0-t)of ZSP1601 [ Time Frame: UP to 2, 16, 9 days for SAD, MAD, FE part respectively ]
    AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.
  • AUCinf(AUC0-∞)of ZSP1601 [ Time Frame: UP to 2, 16, 9 days for SAD, MAD, FE part respectively ]
    AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).
  • Cmax of ZSP1601 [ Time Frame: UP to 2, 16, 9 days for SAD, MAD, FE part respectively ]
    Cmax is defined as the maximum observed concentration of drug in plasma.
  • Tmax of ZSP1601 [ Time Frame: UP to 2, 16, 9 days for SAD, MAD, FE part respectively ]
    Tmax is defined as the time to maximum concentration.
  • t1/2z of ZSP1601 [ Time Frame: UP to 2, 16, 9 days for SAD, MAD, FE part respectively ]
    t1/2z is defined as the time to decline half of the drug concentration in plasma.
  • Single-dose PK Parameter: Ae of ZSP1601 [ Time Frame: Up to Day 2 post-dose ]
    Ae is defined as the amount of unchanged drug excreted in urine or faeces after administration.
  • Single-dose PK Parameter: Fe0-t of ZSP1601 [ Time Frame: Up to Day 2 post-dose ]
    Fe0-t is defined as the cumulative excretion rate of the drug in urine and feces.
  • CL/F of ZSP1601 [ Time Frame: UP to 2, 16, 9 days for SAD, MAD, FE part respectively ]
    CL/F is defined as the ratio of total clearance(Cl) to bioavailability(F).
  • λz of ZSP1601 [ Time Frame: UP to 2, 16, 9 days for SAD, MAD, FE part respectively ]
    λz is defined as the ratio between the elimination of compound per unit time and the total amount of compound.
  • CLr of ZSP1601 [ Time Frame: UP to 2, 16, 9 days for SAD, MAD, FE part respectively ]
    CLr is defined as how many milliliters of plasma in which some substance can be completely eliminated in the unit time (per minute) of two kidneys
  • Multiple-dose plasma PK parameter: Rac of ZSP1601 at steady state [ Time Frame: Up to 16days ]
    Rac (Accumulation Index) is defined as the ratio between AUC0-XX in Day XX and AUC0-XX in Day1
  • Multiple-dose plasma PK parameter: DF of ZSP1601 at steady state [ Time Frame: Up to 16 days ]
    DF is defined as the percentage of fluctuation in steady state is 100 * (Cmax, ss - Cmin, ss)/Cavg, ss.
  • Multiple-dose plasma PK parameter: Cmin of ZSP1601 at steady state [ Time Frame: Up to 16days ]
    Cmin is defined as the minimum observed concentration of drug in plasma at steady state.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
  • AUClast(AUC0-t)of ZSP1601 [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
    AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.
  • AUCinf(AUC0-∞)of ZSP1601 [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
    AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).
  • Cmax of ZSP1601 [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
    Cmax is defined as the maximum observed concentration of drug in plasma.
  • Tmax of ZSP1601 [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
    Tmax is defined as the time to maximum concentration.
  • t1/2z of ZSP1601 [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
    t1/2z is defined as the time to decline half of the drug concentration in plasma.
  • Single-dose PK Parameter: Ae of ZSP1601 [ Time Frame: Up to Day 4 post-dose ]
    Ae is defined as the amount of unchanged drug excreted in urine or faeces after administration.
  • Single-dose PK Parameter: Fe0-t of ZSP1601 [ Time Frame: Pre-dose (within 30 min before dosing) and 10min, 20min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h(Day2), 48h(Day3), 72h(Day4) post-dose ]
    Fe0-t is defined as the cumulative excretion rate of the drug in urine and feces.
  • CL/F of ZSP1601 [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
    CL/F is defined as the ratio of total clearance(Cl) to bioavailability(F).
  • λz of ZSP1601 [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
    λz is defined as the ratio between the elimination of compound per unit time and the total amount of compound.
  • CLr of ZSP1601 [ Time Frame: UP to 4, 10, 11 days for SAD, MAD, FE part respectively ]
    CLr is defined as how many milliliters of plasma in which some substance can be completely eliminated in the unit time (per minute) of two kidneys
  • Multiple-dose plasma PK parameter: Rac of ZSP1601 at steady state [ Time Frame: Up to 10days ]
    Rac (Accumulation Index) is defined as the ratio between AUC0-XX in Day XX and AUC0-XX in Day1
  • Multiple-dose plasma PK parameter: DF of ZSP1601 at steady state [ Time Frame: Up to 10 days ]
    DF is defined as the percentage of fluctuation in steady state is 100 * (Cmax, ss - Cmin, ss)/Cavg, ss.
  • Multiple-dose plasma PK parameter: Cmin of ZSP1601 at steady state [ Time Frame: Up to 10days ]
    Cmin is defined as the minimum observed concentration of drug in plasma at steady state.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study in Chinese Healthy Adults to Evaluate the Safety, Tolerability and Pharmacokinetics on ZSP1601, and the Effect of Food on ZSP1601 Pharmacokinetics
Official Title  ICMJE 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Masking for Participant, Investigator and Clinical Research Associate
Primary Purpose: Treatment
Condition  ICMJE Nonalcoholic Steatohepatitis (NASH)
Intervention  ICMJE
  • Drug: ZSP1601 25 mg
    ZSP1601 tablet administered orally once daily under fasted condition
  • Drug: Placebo 25mg
    Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition
  • Drug: ZSP1601 50 mg
    ZSP1601 tablet administered orally once daily under fasted condition
  • Drug: Placebo 50 mg
    Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition
  • Drug: ZSP1601 100 mg
    ZSP1601 tablets administered orally once daily in the fasting state
  • Drug: Placebo 100 mg
    Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state
  • Drug: ZSP1601 175 mg
    ZSP1601 tablets administerekd orally once daily under fasted condition
  • Drug: Placebo 175 mg
    Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition
  • Drug: ZSP1601 275 mg
    ZSP1601 tablets administered orally once daily in the fasting state
  • Drug: Placebo 275 mg
    Participants will receive placebo matching to ZSP1601 orally once daily in the fasting state
  • Drug: ZSP1601 350 mg
    ZSP1601 tablets administered orally once daily under fasted condition
  • Drug: Placebo 350mg
    Participants will receive placebo matching to ZSP1601 orally once daily under fasted condition
  • Drug: ZSP1601 100 mg
    ZSP1601 tablets administered orally once daily under fasted or fed condition
  • Drug: Placebo 100mg
    Participants will receive placebo matching to ZSP1601 orally once daily under fasted or fed condition
  • 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).
  • 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).
  • 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).
  • 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).
Study Arms  ICMJE
  • Experimental: ZSP1601(single dose)-25 mg while fasted(Cohort 1)
    ZSP1601 25 mg /Placebo
    Interventions:
    • Drug: ZSP1601 25 mg
    • Drug: Placebo 25mg
  • Experimental: 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.

    Interventions:
    • Drug: ZSP1601 50 mg
    • Drug: Placebo 50 mg
  • Experimental: 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.

    Interventions:
    • Drug: ZSP1601 100 mg
    • Drug: Placebo 100 mg
  • Experimental: 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.

    Interventions:
    • Drug: ZSP1601 175 mg
    • Drug: Placebo 175 mg
  • Experimental: 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.

    Interventions:
    • Drug: ZSP1601 275 mg
    • Drug: Placebo 275 mg
  • Experimental: 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.

    Interventions:
    • Drug: ZSP1601 350 mg
    • Drug: Placebo 350mg
  • Experimental: 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.

    Interventions:
    • Drug: ZSP1601 100 mg
    • Drug: Placebo 100mg
  • Experimental: 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.

    Interventions:
    • Drug: ZSP1601 50 mg
    • Drug: Placebo 50 mg
  • Experimental: 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.

    Interventions:
    • Drug: ZSP1601 100 mg
    • Drug: Placebo 100 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 31, 2018)
94
Original Estimated Enrollment  ICMJE
 (submitted: January 2, 2018)
100
Estimated Study Completion Date  ICMJE March 2019
Estimated Primary Completion Date March 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

  • Eligible subjects must not meet any of the following 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 QTcB>470ms in males,or QTcB>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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Yanhua Ding, MD +86-18186879768 dingyanhua2003@126.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03392779
Other Study ID Numbers  ICMJE ZSP1601-16-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Guangdong Zhongsheng Pharmaceutical Co., Ltd.
Study Sponsor  ICMJE Guangdong Zhongsheng Pharmaceutical Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yanhua Ding, MD First Hospital of Jilin University
PRS Account Guangdong Zhongsheng Pharmaceutical Co., Ltd.
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP