Safety and Pharmacokinetic of Donepezil Pamoate in Healthy Subjects

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

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

Study Overview

• Status: Completed
• Conditions: AD
• Intervention / Treatment: Drug: Donepezil Pamoate for Injection 17mg; Drug: Donepezil Pamoate for Injection 34mg; Drug: Donepezil Hydrochloride 5mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 57 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders
2. Resting pulse rate <55/min or >100/min; Sitting systolic blood pressure <90mmHg or >140mmHg, diastolic blood pressure <60mmHg or >90mmHg
3. ALT or Cr, BUN exceeding the upper limit of normal value; test results of urine protein was "++"
4. 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
5. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody
6. History or presence of drug or alcohol abuse
7. Positive pregnancy test result, or plan to be pregnant if female
8. An unwillingness or inability to comply with food and beverage restrictions within 24 hours prior to dosing
9. Participation in any other investigational drug trial within 30 days prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Synergy Pharmaceutical Sciences Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2019
• Primary Completion (Actual): August 6, 2020
• Study Completion (Actual): September 11, 2020

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: April 28, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 25, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: DON101-CTP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No