to Evaluate the Safety, Tolerability and Pharmacokinetics of Four Formulations of LY03009 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to Evaluate the Safety, Tolerability and Pharmacokinetics of Four Formulations of LY03009 in Healthy Volunteers.

Detailed Description
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This is an open-label study in healthy volunteers to evaluate the safety, tolerability and pharmacokinetics of four formulations of LY03009 (F1, F2, F3, F4) after a single intramuscular injection. Approximately 40 healthy subjects are planned to be enrolled in this study and assigned to four cohorts (F1, F2, F3, F4) sequentially, 10 subjects per group at a fixed dose of 112 mg for F1 F3 and 224 mg for F4. Each subject will receive only one dose in this study.

Official Title
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An Open-Label Study in Healthy Volunteers to Evaluate the Safety, Tolerability and Pharmacokinetics of Four Formulations of LY03009 After a Single Intramuscular Injection

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: LY03009 F1
* Drug: LY03009 F2
* Drug: LY03009 F3
* Drug: LY03009 F4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria： To participate in the study, subjects must meet all of the following inclusion criteria: Willing and capable of giving signed written informed consent; Male or female, 18-65 years of age (inclusive) at screening; Body mass index (BMI, weight [kg]/height [m]2) between 18.0 and 30.0 kg/m2, inclusive; The screening results within the normal range or outside the normal range but assessed as clinically non-significant by the Investigator based on detailed medical history, clinical laboratory tests, vital signs, physical examination, and 12-lead ECG; QTcF ≤450 msec for male subjects, and QTcF ≤470 msec for female subjects. Males who are willing to remain abstinent; or if engaging in sexual intercourse with a female partner of childbearing potential, willing to use a condom in addition to having the female partner use a highly effective method of contraception throughout the study and until at least 3 months after the end of the study. This requirement does not apply to subjects in a same sex relationship or subjects with female partners of non-childbearing potential. Male subjects must also be willing to not donate sperm throughout the study and until at least 3 months after the end of the study. Exclusion Criteria： Subjects meeting any of the following criteria will be excluded from the study: With history of history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, neurologic, bronchopulmonary, immunologic, and/or lipid metabolism disorders, and/or drug hypersensitivity, or any other condition that, in the opinion of the PI, would jeopardize the safety of the subject, affect the validity of the study results, or impair the ability to provide informed consent; Hospital admission or major surgery within 3 months prior to screening, or plan to have surgery before the completion of study; Receipt of another investigational product within 1 month or 5 half-lives of the other investigational product, whichever is longer, before study drug administration in this study; Unwillingness or inability to comply with food and beverage restrictions during study participation; Have a history of significant drug sensitivity or drug allergy, or known hypersensitivity to the study drugs, the metabolite or formulation excipients; Malignancy within 5 years of screening visit (excluding non-melanoma skin cancer and cervical carcinoma in situ that has been completely resected); Subject who is considered unsuitable for participating in the study in the opinion of investigator. Recent administration of live vaccine within 3 months prior to dosing and until at least 30 days after the completion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Formulation 1<br>a single dose of LY03009 F1 | Drug: LY03009 F1<br>* a single dose of LY03009 F1<br>|
| Experimental: Formulation 2<br>a single dose of LY03009 F2 | Drug: LY03009 F2<br>* a single dose of LY03009 F2<br>|
| Experimental: Formulation 3<br>a single dose of LY03009 F3 | Drug: LY03009 F3<br>* a single dose of LY03009 F3<br>|
| Experimental: Formulation 4<br>a single dose of LY03009 F4 | Drug: LY03009 F4<br>* a single dose of LY03009 F4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events | Frequency of adverse events. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Frequency of adverse events | Frequency of adverse events. Apply to cohort F4. | From screening up to day 161 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum (peak) plasma concentration (Cmax) of LY03009 | Maximum (peak) plasma concentration (Cmax) of LY03009. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Maximum (peak) plasma concentration (Cmax) of LY03009 | Maximum (peak) plasma concentration (Cmax) of LY03009. Apply to cohort F4 | From screening up to day 161 | 
| Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) of LY03009 | Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) of LY03009.Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) of LY03009 | Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) of LY03009.Apply to cohort F4 | From screening up to day 161 | 
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) of LY03009 | Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) of LY03009.Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) of LY03009 | Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) of LY03009. Apply to cohort F4 | From screening up to day 161 | 
| Time to maximum plasma concentration (Tmax) of LY03009 | Time to maximum plasma concentration (Tmax) of LY03009. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Time to maximum plasma concentration (Tmax) of LY03009 | Time to maximum plasma concentration (Tmax) of LY03009. Apply to cohort F4 | From screening up to day 161 | 
| Terminal elimination half-life (t1/2) of LY03009 | Terminal elimination half-life (t1/2) of LY03009. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Terminal elimination half-life (t1/2) of LY03009 | Terminal elimination half-life (t1/2) of LY03009.Apply to cohort F4 | From screening up to day 161 | 
| Apparent clearance (CL/F) of LY03009 | Apparent clearance (CL/F) of LY03009. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Apparent clearance (CL/F) of LY03009 | Apparent clearance (CL/F) of LY03009. Apply to cohort F4 | From screening up to day 161 | 
| Apparent volume of distribution (Vz/F) of LY03009 | Apparent volume of distribution (Vz/F) of LY03009. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Apparent volume of distribution (Vz/F) of LY03009 | Apparent volume of distribution (Vz/F) of LY03009. Apply to cohort F4 | From screening up to day 161 | 
| Terminal elimination rate constant (λz) of LY03009 | Terminal elimination rate constant (λz) of LY03009. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Terminal elimination rate constant (λz) of LY03009 | Terminal elimination rate constant (λz) of LY03009. Apply to cohort F4 | From screening up to day 161 | 
| Mean residence time (MRT) of LY03009 | Mean residence time (MRT) of LY03009. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Mean residence time (MRT) of LY03009 | Mean residence time (MRT) of LY03009. Apply to cohort F4 | From screening up to day 161 | 
| Area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCex) of LY03009 | Area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCex) of LY03009. Apply to cohort F1, cohort F2 and cohort F3. | From screening up to day 98 | 
| Area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCex) of LY03009 | Area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCex) of LY03009. Apply to cohort F4 | From screening up to day 161 |