Tolerability, Efficacy, and PK of ZSP1601 in Patients With Non-Alcoholic Steatohepatitis (NASH)
Study Details
Study Description
Brief Summary
Double-blind, randomized, placebo-controlled study to explore the safety, tolerability PK characteristics and early efficacy of ZSP1601 tablets in patients with non-alcoholic steatohepatitis (NASH).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: ZSP1601-Dose 1 ZSP1601-50mg once daily |
Drug: ZSP1601
ZSP1601 tablets be taken orally for 28 days.
Drug: ZSP1601 Placebo
Subjects will receive matching placebo of ZSP1601
|
Experimental: ZSP1601-Dose 2 ZSP1601-50mg twice daily |
Drug: ZSP1601
ZSP1601 tablets be taken orally for 28 days.
Drug: ZSP1601 Placebo
Subjects will receive matching placebo of ZSP1601
|
Experimental: ZSP1601-Dose 3 ZSP1601-100mg once daily |
Drug: ZSP1601
ZSP1601 tablets be taken orally for 28 days.
Drug: ZSP1601 Placebo
Subjects will receive matching placebo of ZSP1601
|
Placebo Comparator: Placebo Placebo |
Drug: ZSP1601 Placebo
Subjects will receive matching placebo of ZSP1601
|
Outcome Measures
Primary Outcome Measures
- Number and severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE) following oral doses of ZSP1601 and placebo. [Initiation of study treatment (Day 1) up to 2 weeks post-treatment.]
severity of treatment-emergent adverse events (TEAEs) and Serious Adverse Events(SAE)
Secondary Outcome Measures
- MRI-PDFF [Baseline and Day 28.]
liver fat content with Magnetic resonance imaging proton density fat fraction (MRI-PDFF)
- TNF-α [Baseline and Day 28.]
Tumor necrosis factor alpha level in serum
- ALT [Baseline and Day 28.]
serum Alanine Aminotransferase
- AST [Baseline and Day 28.]
serum Aspartate Aminotransferase
- Tmax [Day1 and day 14]
The time after dosing when Cmax occurs (Tmax)
- Cmax [Day1 and day 14]
Maximum Contentration
- t1/2z [Day1 and day 14]
t1/2z is defined as the time to decline half of the drug concentration in plasma.
- Rac of Cmax [Day1 and day 14]
Rac of ZSP1601 Peak Plasma Concentration at steady state
- DF of ZSP1601 at steady status [Day1 and day 14]
Multiple-dose plasma PK parameter: DF of ZSP1601 at steady status
- AUClast(AUC0-t) [Baseline (0h) and day 14]
AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.
- Rac of AUC [Day1 and day 14]
RAC of ZSP1601 Area under the plasma concentration versus time curve at steady state
Other Outcome Measures
- AUC(inf) [Day1 and day 14]
Area under the curve extrapolated until time is infinity (AUCinf)
Eligibility Criteria
Criteria
Inclusion Criteria:
- Subjects are required to meet the following criteria in order to be included in the trial:
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Signature signed informed consent before the trial, and fully understood the content, process and possible adverse reactions.
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Subjects must be willing and able to adhere to the visit schedule and protocol requirements and be available to complete the study.
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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.
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Male and female subjects aged 18-65 (including 18 and 65).
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B ultrasound confirmed fatty liver.
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NASH diagnosis or NASH phenotypic diagnosis.
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Liver fat ≥10% at baseline (MRI-PDFF)
Exclusion Criteria:
- Eligible subjects must not meet any of the following exclusion criteria:
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Excessive drinking for 3 consecutive months within 1 year before screening.
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Allergic constitution.
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Subjects who donated blood or bleeding profusely(> 400 mL)in the 3 months preceding study screening.
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Subjects having a history of bariatric surgery or preparing for bariatric surgery recently.
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Subjects having a history of liver transplantation or plans for liver transplantation
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Any diseases that increase the risk of bleeding, such as hemorrhoids, acute gastritis or gastric and duodenal ulcers.
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Liver biopsy indicates cirrhosis or previous clinical diagnosis of cirrhosis.
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Type 1 diabetes mellitus.
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Uncontrolled type 2 diabetes mellitus (HbA1c≥8.0%)。
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Any clinically significant abnormality upon physical examination or in the clinical laboratory tests, history or presence of other causes of liver disease,but not limited to above disorders: hepatitis b or hepatitis c virus (HCV) infection and chronic alcoholic liver disease, drug-induced liver disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson 's disease, alpha 1 - antitrypsin deficiency, liver, obvious abnormal liver function (ALT and AST acuity 5 x ULN or TBIL acuity 1.5 x ULN), etc.
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Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs.
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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 2 weeks prior to screening.
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Participated in another clinical research study and received any investigational products within 3 months prior to dosing.
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Presence of clinically significant abnormalities in ECG or QTcB>450ms in males,or QTcB>470ms in females.
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HIV positive.
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Clinically significant nephropathy or renal dysfunction, blood creatinine
1.5×ULN, eGFR< 60 mL/min/1.73m2 [calculation formula: Ccr:(140-age)× weight (kg) /0.818×Scr(mumol /L), female ×0.85].
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Platelet count <100×109/L.
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Antinuclear antibody (ANA) confirmed positive and clinically significant.
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Abnormal TSH with clinical significance.
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Female during pregnancy and lactation or positive serum pregnancy test.
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Patients with contraindication of MRI scan.
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Take any product contains alcohol within 24 hours prior to dosing.
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Have chocolate, any food or beverage that contains caffeine or xanthine within 24 hours prior to dosing.
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Positive for urine drug screening or history of substance abuse for a period of 5 consecutive years before screening.
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Any acute illness or concomitant medication from screening to first dosing.
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As judged by the researcher, it is not suitable to join the clinical researcher.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | The First Hospital of Jilin University | Changchun | Jilin | China | 130021 |
Sponsors and Collaborators
- Guangdong Raynovent Biotech Co., Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZSP1601-18-02