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The study consists of 10 dose groups, 8 subjects in each group (male or female), randomly assigned to study drug or placebo group to evaluate the safety, tolerability and pharmacokinetics characteristics.
The dose levels are planned at 1 mg, 2 mg, 4 mg, 8 mg, 15 mg, 25 mg,40 mg, 60 mg ,90 mg and 120mg. 6 subjects in each group will receive LV232 tablets and 2 subjects will receive placebo. The subject number of single dose group may increase or decrease depending on the safety and PK data obtained.1 mg dose group will be given by sentinel administration (i.e. 1 study drug, 1 placebo). Subjects who receive sentinel administration will be observed for 48 hours and investigator will evaluate the safety parameters (including symptoms, vital signs, physical examination, etc.).Based on observed tolerability and safety data or obtained PK data, adjustments are allowed at all dose levels in the clinical trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LV232 | Experimental | Subjects will receive LV232 orally for single dose. |
|
| Placebo | Experimental | Subjects will receive placebo orally for single dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LV232 | Drug | Drug: LV232 1mg,2mg,4mg,8mg,15mg,25mg,40mg,60mg,90mg and 120mg |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | Incidence of Treatment-Emergent Adverse Events | 7 days after treatment |
| Cmax | maximum observed plasma concentration | 48 hours after administration |
| AUC0-t | area under the plasma concentration time curve from time zero to the last | 48 hours after administration |
| AUC0-∞ | area under the plasma concentration time curve from time zero to infinity | 48 hours after administration |
| AUC0-24h | area under the plasma concentration time curve from time zero to 24 hours | 48 hours after administration |
| Tmax | time at which Cmax occurs | 48 hours after administration |
| t1/2 | half life of elimination | 48 hours after administration |
| CL/F | apparent clearance | 48 hours after administration |
| Vd/F |
| Measure | Description | Time Frame |
|---|---|---|
| structural of metabolites | Structure of main metabolites of LV232 in plasma, feces and urine | From time zero up to 96 hours post-dose following oral administration |
| Ae | Cumulative excretion of LV232 and major metabolites in feces and urine |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Chen Yu | Shanghai Xuhui Central Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Xuhui Central Hospital | Shanghai | Shanghai Municipality | 201900 | China |
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| Placebo |
| Drug |
Placebo:1mg,2mg,4mg,8mg,15mg,25mg,40mg,60mg,90mg and 120mg |
|
apparent volume of distribution during the terminal phase
| 48 hours after administration |
| Ke | elimination rate constant | 48 hours after administration |
| MRT | mean Resident Time | 48 hours after administration |
| BP | Blood Plasma Ratio | 48 hours after administration |
| BRPP | binding rate of plasma protein | 48 hours after administration |
| From time zero up to 96 hours post-dose following oral administration |
| Fe% | Percentage of LV232 and major metabolites in feces and urine | From time zero up to 96 hours post-dose following oral administration |
| CLr | renal clearance rate | From time zero up to 72 hours post-dose following oral administration |
| Genetic polymorphisms in drug metabolism | Influence of genetic polymorphisms in drug metabolism enzymes on pharmacokinetics and safety | Before administration |