Study of the Safety, Tolerability, and Pharmacokinetics of LV232 Capsules in Chinese Healthy Volunteers

Study Overview
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Brief Summary
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The study consists of 6 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.

Detailed Description
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The dose levels are planned at 1 mg, 2 mg, 4 mg, 8 mg, 15 mg and 20 mg. 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.

Official Title
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A Randomized, Double-blind, Placebo-Controlled, Single-Centre,Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of LV232 Capsules in Chinese Healthy Volunteers

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: LV232
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to 45 years old, males or females; Body weight no less than 50.0 kg for male, no less than 45.0 kg for female,Body Mass Index of 19.0 to 26.0kg/m2; Physical examination, vital signs examination, laboratory examination, electrocardiogram examination and B-ultrasound examination results were normal or abnormal without clinical significant; Subjects who are willing to take effective contraceptive during the study and within 3 months after the study completed; Subjects who are able to understand and follow study plans and instructions; Subjects who have voluntarily decided to participate in this study, and signed the informed consent form. Exclusion Criteria: Subjects with hypersensitivity to LV232 or any of the excipients; Subjects with allergic diseases or allergic constitution; Subjects with skin diseases or a history of skin allergies; Subjects with central nervous system, cardiovascular system, gastrointestinal, respiratory system, urinary, Hematologic System, metabolic disorders that require medical intervention or other diseases (such as psychiatric history) that are not suitable for clinical trials; Blood donation or blood loss ≥ 400 mL within 3 months , or have a history of blood product use history Subjects who have participated in clinical trials of other drugs within 3 months before screening; Subjects who have taken any prescription drugs, over-the-counter drugs, Chinese herbal medicines, or health products orally within 2 weeks before screening; Drug or alcohol addicts within 1 year prior to screening, who drink at least twice a day or more than 14 units per week, or who are addicted to alcohol (1 unit ≈200 mL beer with 5% alcohol content, 25 mL spirits with 40% alcohol content or 85 mL wine with 12% alcohol content); Subjects who smoked more than 10 cigarettes or equivalent amounts of tobacco a day within one year before screening; Subjects who can't quit smoking and drinking during the experiment; Subjects who are positive for hepatitis B virus surface antigen, hepatitis C virus antibody, Treponema pallidum antibody (TPPA) or human immunodeficiency virus antibody (Anti-HIV); Abnormal and clinically significant chest radiographs (anteroposterior); B ultrasound examination showed moderate to severe fatty liver; Pregnant or lactating woman or male subjects whose spouse has a child care plan within 3 months; The investigator believes that there are other factors that are not suitable for participating in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LV232<br>Subjects will receive LV232 orally for single dose. | Drug: LV232<br>* Drug: LV232 1mg Group: 6 subjects will receive LV232 1mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo Drug: LV232 2mg Group: 6 subjects will receive LV232 2mg, orally; 2 subjects will receive placebo, orally. Other Names: Placebo Drug: LV232 4mg Group: 6 subjects will receive LV232 4mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo Drug: LV232 8mg Group: 6 subjects will receive LV232 8mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo Drug: LV232 15mg Group: 6 subjects will receive LV232 15mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo Drug: LV232 20mg Group: 6 subjects will receive LV232 20mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo<br>|
| Experimental: Placebo<br>Subjects will receive placebo orally for single dose. | Drug: Placebo<br>* Drug: LV232 1mg Group: 6 subjects will receive LV232 1mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo Drug: LV232 2mg Group: 6 subjects will receive LV232 2mg, orally; 2 subjects will receive placebo, orally. Other Names: Placebo Drug: LV232 4mg Group: 6 subjects will receive LV232 4mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo Drug: LV232 8mg Group: 6 subjects will receive LV232 8mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo Drug: LV232 15mg Group: 6 subjects will receive LV232 15mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo Drug: LV232 20mg Group: 6 subjects will receive LV232 20mg, orally; 2 subjects will receive placebo, orally. Other Names:Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LV232, Phase I, dose-escalation, Tolerability, Pharmacokinetic