Safety, Tolerability and Pharmacokinetics of AD16 Tablets After MAD in Healthy Chinese Adult Subjects (MAD)

Safety, Tolerability and Pharmacokinetics of AD16 Tablets After Multiple Administration in Healthy Chinese Adult Subjects

This single-center, randomized, placebo-controlled, double-blind, dose-increasing study was designed to evaluate the safety, tolerability, and pharmacokinetics of multiple successive dosing in healthy Chinese adult subjects.In this study, 20 healthy adult subjects were enrolled in a multi-dose study in the 30mg and 40mg groups.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: AD16 30mg、40mg; Drug: AD16 Placebo 30mg、40mg

Detailed Description

In this study, subjects were given multiple doses in the corresponding dose group

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Changsha, China
    • The Central South University Xiang Ya Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy subjects were aged 18-45 years (including boundary values), male and female.
2. Weight ≥50kg (male) or ≥45kg (female), and body mass index (BMI) of 19-24kg/m2 (including the boundary values at both ends).
3. Have fully understood this study, voluntarily participated in it, and signed the Informed Consent.
4. Subjects are able to communicate well with researchers and complete the study according to protocol.
5. The subjects were deemed to be in good health based on physical examination, medical history, vital signs, electrocardiogram, chest X-ray, abdominal ultrasound, and laboratory tests.
6. Subject (including partner) is willing to have no pregnancy plan for the next 30 days (female subject) or 90 days (male subject) and is willing to use effective contraception.

Exclusion Criteria:

1. Positive for hepatitis B surface antigen, hepatitis C antibody, syphilis antibody or HIV antibody.
2. The patient has symptoms or related history of any serious disease, including but not limited to heart, liver, kidney, or other acute or chronic digestive tract or respiratory tract diseases, as well as diseases of the blood, endocrine, neurological, psychiatric and other systems, or any other disease or physiological condition that can interfere with the study results.
3. A history of postural hypotension with frequent episodes.
4. A history of frequent nausea or vomiting due to any cause.
5. Any clear history of drug or food allergies, especially allergies to ingredients similar to the drugs in this study.
6. Have special dietary requirements and cannot comply with the uniform diet provided by the clinical research center.
7. Previous drug abuse history or positive urine drug screening during screening period.
8. Smokers who smoked more than 5 cigarettes a day in the 3 months before the test.
9. Heavy drinkers or regular drinkers in the 6 months prior to the study screening, who drank more than 14 units of alcohol per week (1 unit of alcohol ≈360 mL beer or 45 mL 40% spirits or 150 mL wine) or had a positive alcohol breath test during the screening period.
10. Excessive consumption of tea, coffee (more than 6 cups) and/or caffeinated beverages (more than 1L) per day.
11. Take food or drink rich in xanthine, grapefruit or alcohol, caffeine (e.g., dragon fruit, mango, grapefruit, chocolate, coffee or tea) within 48 hours before administration.
12. Surgical procedures, transfusions of blood or blood components in the month prior to study screening.
13. Blood loss or donation of more than 400 mL in the 2 months prior to screening.
14. Participated in other clinical studies and took experimental drugs within 3 months prior to study screening.
15. Study participants who had received any medication in the 28 days prior to screening.
16. Pregnant or lactating women or women who have had unprotected sex within 14 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AD16; AD16 tablets should be administered only in the morning on the day of the first dose and on the ninth day after the first dose. Fasting is required for at least 10 h before administration.Two dosing cohorts received AD16 From the third day to the eighth day, the medicine was administered twice a day, 1 h before breakfast, 1 h before dinner or 2 h after dinner, with a 12 h interval (time window ±1 h).The duration of oral AD16 tablets was nine days.	Drug: AD16 30mg、40mg; AD16 was taken continuously.Firstly, a 30 mg (bid) multiple dose study was conducted, followed by a 40 mg (bid) multiple dose study
Placebo Comparator: AD16 placebo; AD16 placebo tablets should be administered only in the morning on the day of the first dose and on the ninth day after the first dose. Fasting is required for at least 10 h before administration.Two dosing cohorts received AD16 placebo From the third day to the eighth day, the medicine was administered twice a day, 1 h before breakfast, 1 h before dinner or 2 h after dinner, with a 12 h interval (time window ±1 h).The duration of oral AD16 placebo tablets was nine days.	Drug: AD16 Placebo 30mg、40mg; AD16 placebo was taken continuously.Firstly, a 30 mg (bid) multiple dose study was conducted, followed by a 40 mg (bid) multiple dose study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	The number of adverse events	day-7 to day11
Serious adverse events	The number of serious adverse events	day-7 to day11
Number of participants with abnormal laboratory test results	Laboratory tests include Blood routine, blood biochemistry, coagulation function and urine routine, etc.	Screening period (day-7 to day-2) and day11
Number of participants with abnormal vital signs	Pulse, blood pressure, body temperature and respiratory rate were observed at different time points before and after medication.	Screening period（day-7 to day-1）、days1、4、5、6、8、9
Number of participants with abnormal 12-lead electrocardiogram readings	Abnormal12-lead electrocardiogram	Screening period（day-7 to day-2）、days1、6、11
Number of participants with abnormal physical examination findings	The skin, mucosa, lymph nodes, head, neck, chest, abdomen, spine/limbs and nervous system were observed at different time points before and after medication.	Screening period（day-7 to day-2）、days11
Concomitant medication	Any concomitant medication	Up to day 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax of AD16	Time to reach the maximum (peak) plasma concentration following drug administration	Up to day 11
Cmax of AD16	Maximum (peak) plasma drug concentration	Up to day 11
t1/2z of AD16	Elimination half-life (to be used in a one-compartment or noncompartmental model)	Up to day 11
AUC 0-∞ of AD16	Area under the plasma concentration-time curve（AUC） from time zero to infinity	Up to day 11
AUC 0-t of AD16	Area under the plasma concentration-time curve（AUC） from time zero to time t	Up to day 11
Vd/F of AD16	Apparent volume of distribution after non-intravenous administration	Up to day 11
CL/F of AD16	CL/F is defined as the ratio of total clearance(CL) to bioavailability(F).	Up to day 11
λz of AD16	Terminal disposition rate constant/terminal rate constant	Up to day 11
AUC 0-48h of AD16	Area under the plasma concentration-time curve from time zero to time 48h	Up to day 11
AUC_%Extrap of AD16	AUC_%Extrap is residual area percentage	Up to day 11
Tmax,ss of AD16	Time to reach the maximum (peak) plasma concentration following drug administration at steady state	Up to day 11
Cmax, ss of AD16	Maximum (peak) steady-state plasma drug concentration during a dosage interval	Up to day 11
Cavg,ss of AD16	Cavg,ss is the steady-state mean concentration	Up to day 11
t1/2,ss of AD16	Elimination half-life（steady state ）	Up to day 11
AUC 0-τ,ss of AD16	The area under the plasma concentration-time curve during a dosing interval at steady state	Up to day 11
AUC 0-48h,ss of AD16	Area under the plasma concentration-time curve from the last dose to 48 h	Up to day 11
AUC 0-∞,ss of AD16	The area under the plasma concentration-time curve is extrapolated from the last dose to infinity	Up to day 11
CL/F,ss of AD16	CL/F is defined as the ratio of total clearance(CL) to bioavailability(F)（steady state ）	Up to day 11
Rac of AD16	Rac is accumulation ratio	Up to day 11
DF of AD16	Degree of fluctuation（DF）Percentage fluctuation in steady state = 100 × (Cmax,ss -Cmin,ss)/Cavg,ss	Up to day 11
Vd/F,ss of AD16	Apparent volume of distribution after non-intravenous administration （steady state ）	Up to day 11

Collaborators and Investigators

• Sponsor: South China Center For Innovative Pharmaceuticals
• Collaborators: Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2020
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 28, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: SCCIP-AD16-2018-03

Drug and device information, study documents

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