A Single Dose Escalation Study of HHT201 in Healthy Subjects

Phase 1

Not yet recruiting

• Conditions: Alzheimer Disease
• Interventions: Drug: Donepezil Dihydroxynaphthalate for Injection

• Registration Number: NCT06373094
• Lead Sponsor: Shanghai Synergy Pharmaceutical Sciences Co., Ltd.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-19
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-17
• Last Update Submitted: 2024-04-17
• Study First Posted: 2024-04-18
• Last Update Posted: 2024-04-18
• Study Start: 2024-06-01
• Primary Completion: 2025-03-31
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. Chinese healthy subjects, both male and female;
2. 20 years old ≤ 60 years old;
3. The weight of women is not less than 45 kg, the weight of men is not less than 50 kg, and the BMI is between 19 and 28 (including the upper and lower limits);
4. Understand and sign informed consent to participate in clinical trials voluntarily.

Exclusion Criteria

1. Patients with a history of cardiovascular, respiratory, liver, kidney, endocrine system, digestive system, blood and lymphatic system, immune system, nervous system, skeletal system, psychiatric and other major diseases, who were judged not suitable for participation in this study;
2. Comprehensive physical examination, laboratory examination, vital signs, or past medical history are judged by clinicians to be abnormal and clinically significant;
3. ALT or Cr, BUN beyond the upper limit of normal values; Urine protein test results were "++";
4. Abnormal electrocardiogram (ECG) during the screening period had clinical significance, such as QTcF interval ≥450 ms in males and QTcF interval ≥470 ms in females, and the researchers considered it inappropriate to be included;
5. Those who had used CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin, or CYP2D6 inhibitors such as fluoxetine and quinidine within 30 days before the screening period, or rifampicin, phenytoin sodium, and carbamazil equal liver drug enzyme inducers, or had taken any prescription drugs, over-the-counter drugs, Chinese herbs, vitamins, or other dietary supplements within two weeks before enrollment;
6. People who have taken food or drink (such as grapefruit) containing enzymes that can induce or inhibit liver metabolism within 1 week before the start of the trial;
7. People who have a history of severe allergy or have a history of allergy to two or more drugs, or to any of the components of Donepezil dihydroxynaphthoate for injection;
8. Patients with positive results of serum virology test [Hepatitis B surface antigen (HBsAg), Hepatitis Be antigen (HBeAg), hepatitis C virus antibody (HCV-IgG), human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody (Anti-TP)];
9. Subjects with smoking history within 2 weeks prior to the screening period or positive results of urine cotinine test during the admission review period;
10. There is a history of alcohol abuse, or during the study period the subjects were unable to avoid drinking in the 24 hours before and during the trial drug administration, or those who tested positive for alcohol breath test;
11. There is a history of drug abuse, and the drug screen test results are positive;
12. Blood pregnancy test positive or breastfeeding women;
13. Contraceptives in which the subject or his or her spouse has a family plan within the next 6 months after the last dose and is unable to use research-approved contraceptives during the study period as directed by the investigator;
14. Blood donation or blood loss ≥400 mL in the 3 months before screening, blood donation ≥200 mL in the 1 month before screening;
15. It is impossible to avoid the use of caffeinated beverages, vigorous exercise, or other factors affecting the absorption, distribution, metabolism, and excretion of the drug within 24 hours before and during the trial;
16. Past or existing sick sinus syndrome or other supratrioventricular conduction heart disease such as sinus or atrioventricular block heart disease; Past or existing digestive tract ulcer, bladder outlet obstruction, history of asthma or obstructive pulmonary disease;
17. Participants who have participated or are participating in other clinical trials within 3 months prior to screening;
18. Subjects with other factors deemed unsuitable for participation in this study by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group 1	Donepezil Dihydroxynaphthalate for Injection	Single dose of 34 mg Donepezil Dihydroxynaphthalate for Injection.
Group 2	Donepezil Dihydroxynaphthalate for Injection	Single dose of 68 mg Donepezil Dihydroxynaphthalate for Injection.
Group 3	Donepezil Dihydroxynaphthalate for Injection	Single dose of 136 mg Donepezil Dihydroxynaphthalate for Injection.
Group 4	Donepezil Dihydroxynaphthalate for Injection	Single dose of 204 mg Donepezil Dihydroxynaphthalate for Injection.
Group 5	Donepezil Dihydroxynaphthalate for Injection	Single dose of 306 mg Donepezil Dihydroxynaphthalate for Injection.
Group 6	Donepezil Dihydroxynaphthalate for Injection	Single dose of 408 mg Donepezil Dihydroxynaphthalate for Injection.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Abnormal Laboratory Values	Up to 42 days	Number of Participants With Abnormal Laboratory Values
Number of Participants With Abnormal Vital signs	Up to 42 days	Number of Participants With Abnormal Vital signs
Number of Participants With Abnormal Physical examination	Up to 42 days	It's comprehensive system check by the doctor.
Adverse events	Up to 42 days	AEs and their incidence
Number of Participants With Abnormal ECG QT Interval	Up to 42 days	Number of Participants With Abnormal ECG QT Interval
VAS	Up to 42 days	Score of Visual Analogue Scale, which is a scale from 0-10, with higher scores indicate more severe.

Secondary Outcome Measures

Name	Time	Method
AUC0-∞ of Donepezil	Blood samples collected over a 42-day period	Area under the concentration-time curve from time zero to infinity.
t1/2z of Donepezil	Blood samples collected over a 42-day period	The time when the concentraion of the drug eliminated to half of the initial.
Vz/F	Blood samples collected over a 42-day period	Apparent volume of distribution
Cmax of Donepezil	Blood samples collected over a 42-day period	Maximum observed concentration of drug substance in plasma.
Tmax of Donepezil	Blood samples collected over a 42-day period	Time when the maximum concentration is acheived
AUC0-t of Donepezil	Blood samples collected over a 42-day period	Area under the blood concentration-time curve from zero to the collection time t of the last measurable concentration.
CLz/F	Blood samples collected over a 42-day period	Apparent clearance

Trial Locations

Locations (1)

Zhejiang Province Taizhou Hospital Luqiao Hospital (Enze Hospital) (Taizhou Hospital Phase I Center); 🇨🇳 Taizhou, Zhe Jiang, China