Safety and Pharmacokinetic of Donepezil Pamoate in Healthy Subjects

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and pharmacokinetic profiles of HHT201 in healthy subjects.

Detailed Description
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The study aims to evaluate the safety, pharmacokinetics and to determine the potential dose limiting toxicity of HHT201 in healthy subjects between the ages of 20-59, 6 in 17mg dose group and 20 in 34mg dose group. Another 12 subjects will be administered a tablet of 5mg Donepezil Hydrochloride to get the PK profile of Donepezil as reference. Eligible subjects will be accepted into the protocol after review and providing voluntary written informed consent forms and completion of a comprehensive medical, physical examination, and routine laboratory assessment.

Official Title
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Evaluation of Safety and Pharmacokinetic Profiles of a Single-dose HHT201 in Healthy Subjects

Conditions
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AD

Intervention / Treatment
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* Drug: Donepezil Pamoate for Injection 17mg
* Drug: Donepezil Pamoate for Injection 34mg
* Drug: Donepezil Hydrochloride 5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese healthy subjects, male or female between the ages of 20 and 60 years A body mass index (BMI), calculated as weight in kg/(height in m)², from 19 to 28 kg/m², and female weight≥45kg, male weight≥50kg Able to provide written informed consent forms Exclusion Criteria: Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders Resting pulse rate <55/min or >100/min; Sitting systolic blood pressure <90mmHg or >140mmHg, diastolic blood pressure <60mmHg or >90mmHg ALT or Cr, BUN exceeding the upper limit of normal value; test results of urine protein was ++ Clinically significant ECG abnormalities in screening or baseline, such as male QTc interval ≥450ms and female QTc interval ≥470ms, and were considered inappropriate for inclusion by the researchers Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody History or presence of drug or alcohol abuse Positive pregnancy test result, or plan to be pregnant if female An unwillingness or inability to comply with food and beverage restrictions within 24 hours prior to dosing Participation in any other investigational drug trial within 30 days prior to screening.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 59 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group 1<br>HHT201 17mg injection | Drug: Donepezil Pamoate for Injection 17mg<br>* A dosage of 17mg HHT201 will be injected into the muscle in the gluteus once.<br>* Other names: HHT201;|
| Experimental: experimental group 2<br>HHT201 34mg injection | Drug: Donepezil Pamoate for Injection 34mg<br>* A dosage of 34mg HHT201 will be injected into the muscle in the gluteus once.<br>* Other names: HHT201;|
| Active Comparator: experimental group 3<br>Donepezil Hydrochloride oral tablet 5mg | Drug: Donepezil Hydrochloride 5mg<br>* A tablet of 5mg Donepezil Hydrochloride will be administered once.<br>* Other names: Aricept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Donepezil | Maximum observed concentration of drug substance in plasma. | Blood samples collected over a 35 days period | 
| Tmax of Donepezil | Time when the maximum concentration is acheived | Blood samples collected over a 35 days period | 
| AUClast of Donepezil | Area under the concentration-time curve from time zero to time of last measurable concentration. | Blood samples collected over a 35 days period | 
| AUC0-∞ of Donepezil | Area under the concentration-time curve from time zero to infinity. | Blood samples collected over a 35 days period | 
| t1/2 of Donepezil | The time when the concentraion of the drug eliminated to half of the initial. | Blood samples collected over a 35 days period |