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

Primary Purpose

Alzheimer Disease

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
AD16 30mg、40mg
AD16 Placebo 30mg、40mg
Sponsored by
Xiangya Hospital of Central South University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Healthy subjects were aged 18-45 years (including boundary values), male and female. Weight ≥50kg (male) or ≥45kg (female), and body mass index (BMI) of 19-24kg/m2 (including the boundary values at both ends). Have fully understood this study, voluntarily participated in it, and signed the Informed Consent. Subjects are able to communicate well with researchers and complete the study according to protocol. 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. 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: Positive for hepatitis B surface antigen, hepatitis C antibody, syphilis antibody or HIV antibody. 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. A history of postural hypotension with frequent episodes. A history of frequent nausea or vomiting due to any cause. Any clear history of drug or food allergies, especially allergies to ingredients similar to the drugs in this study. Have special dietary requirements and cannot comply with the uniform diet provided by the clinical research center. Previous drug abuse history or positive urine drug screening during screening period. Smokers who smoked more than 5 cigarettes a day in the 3 months before the test. 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. Excessive consumption of tea, coffee (more than 6 cups) and/or caffeinated beverages (more than 1L) per day. 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. Surgical procedures, transfusions of blood or blood components in the month prior to study screening. Blood loss or donation of more than 400 mL in the 2 months prior to screening. Participated in other clinical studies and took experimental drugs within 3 months prior to study screening. Study participants who had received any medication in the 28 days prior to screening. Pregnant or lactating women or women who have had unprotected sex within 14 days

Sites / Locations

  • The Central South University Xiang Ya Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AD16

AD16 placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Adverse events
The number of adverse events
Serious adverse events
The number of serious adverse events
Number of participants with abnormal laboratory test results
Laboratory tests include Blood routine, blood biochemistry, coagulation function and urine routine, etc.
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.
Number of participants with abnormal 12-lead electrocardiogram readings
Abnormal12-lead electrocardiogram
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.
Concomitant medication
Any concomitant medication

Secondary Outcome Measures

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

Full Information

First Posted
March 1, 2023
Last Updated
March 28, 2023
Sponsor
Xiangya Hospital of Central South University
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1. Study Identification

Unique Protocol Identification Number
NCT05806177
Brief Title
Safety, Tolerability and Pharmacokinetics of AD16 Tablets After MAD in Healthy Chinese Adult Subjects
Acronym
MAD
Official Title
Safety, Tolerability and Pharmacokinetics of AD16 Tablets After Multiple Administration in Healthy Chinese Adult Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
May 26, 2020 (Actual)
Primary Completion Date
July 31, 2020 (Actual)
Study Completion Date
July 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xiangya Hospital of Central South University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.
Detailed Description
In this study, subjects were given multiple doses in the corresponding dose group

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
A single-center, randomized, placebo-controlled, double-blind, dose-increasing study design
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AD16
Arm Type
Experimental
Arm Description
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.
Arm Title
AD16 placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AD16 30mg、40mg
Intervention Description
AD16 was taken continuously.Firstly, a 30 mg (bid) multiple dose study was conducted, followed by a 40 mg (bid) multiple dose study
Intervention Type
Drug
Intervention Name(s)
AD16 Placebo 30mg、40mg
Intervention Description
AD16 placebo was taken continuously.Firstly, a 30 mg (bid) multiple dose study was conducted, followed by a 40 mg (bid) multiple dose study
Primary Outcome Measure Information:
Title
Adverse events
Description
The number of adverse events
Time Frame
day-7 to day11
Title
Serious adverse events
Description
The number of serious adverse events
Time Frame
day-7 to day11
Title
Number of participants with abnormal laboratory test results
Description
Laboratory tests include Blood routine, blood biochemistry, coagulation function and urine routine, etc.
Time Frame
Screening period (day-7 to day-2) and day11
Title
Number of participants with abnormal vital signs
Description
Pulse, blood pressure, body temperature and respiratory rate were observed at different time points before and after medication.
Time Frame
Screening period(day-7 to day-1)、days1、4、5、6、8、9
Title
Number of participants with abnormal 12-lead electrocardiogram readings
Description
Abnormal12-lead electrocardiogram
Time Frame
Screening period(day-7 to day-2)、days1、6、11
Title
Number of participants with abnormal physical examination findings
Description
The skin, mucosa, lymph nodes, head, neck, chest, abdomen, spine/limbs and nervous system were observed at different time points before and after medication.
Time Frame
Screening period(day-7 to day-2)、days11
Title
Concomitant medication
Description
Any concomitant medication
Time Frame
Up to day 11
Secondary Outcome Measure Information:
Title
Tmax of AD16
Description
Time to reach the maximum (peak) plasma concentration following drug administration
Time Frame
Up to day 11
Title
Cmax of AD16
Description
Maximum (peak) plasma drug concentration
Time Frame
Up to day 11
Title
t1/2z of AD16
Description
Elimination half-life (to be used in a one-compartment or noncompartmental model)
Time Frame
Up to day 11
Title
AUC 0-∞ of AD16
Description
Area under the plasma concentration-time curve(AUC) from time zero to infinity
Time Frame
Up to day 11
Title
AUC 0-t of AD16
Description
Area under the plasma concentration-time curve(AUC) from time zero to time t
Time Frame
Up to day 11
Title
Vd/F of AD16
Description
Apparent volume of distribution after non-intravenous administration
Time Frame
Up to day 11
Title
CL/F of AD16
Description
CL/F is defined as the ratio of total clearance(CL) to bioavailability(F).
Time Frame
Up to day 11
Title
λz of AD16
Description
Terminal disposition rate constant/terminal rate constant
Time Frame
Up to day 11
Title
AUC 0-48h of AD16
Description
Area under the plasma concentration-time curve from time zero to time 48h
Time Frame
Up to day 11
Title
AUC_%Extrap of AD16
Description
AUC_%Extrap is residual area percentage
Time Frame
Up to day 11
Title
Tmax,ss of AD16
Description
Time to reach the maximum (peak) plasma concentration following drug administration at steady state
Time Frame
Up to day 11
Title
Cmax, ss of AD16
Description
Maximum (peak) steady-state plasma drug concentration during a dosage interval
Time Frame
Up to day 11
Title
Cavg,ss of AD16
Description
Cavg,ss is the steady-state mean concentration
Time Frame
Up to day 11
Title
t1/2,ss of AD16
Description
Elimination half-life(steady state )
Time Frame
Up to day 11
Title
AUC 0-τ,ss of AD16
Description
The area under the plasma concentration-time curve during a dosing interval at steady state
Time Frame
Up to day 11
Title
AUC 0-48h,ss of AD16
Description
Area under the plasma concentration-time curve from the last dose to 48 h
Time Frame
Up to day 11
Title
AUC 0-∞,ss of AD16
Description
The area under the plasma concentration-time curve is extrapolated from the last dose to infinity
Time Frame
Up to day 11
Title
CL/F,ss of AD16
Description
CL/F is defined as the ratio of total clearance(CL) to bioavailability(F)(steady state )
Time Frame
Up to day 11
Title
Rac of AD16
Description
Rac is accumulation ratio
Time Frame
Up to day 11
Title
DF of AD16
Description
Degree of fluctuation(DF)Percentage fluctuation in steady state = 100 × (Cmax,ss -Cmin,ss)/Cavg,ss
Time Frame
Up to day 11
Title
Vd/F,ss of AD16
Description
Apparent volume of distribution after non-intravenous administration (steady state )
Time Frame
Up to day 11

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy subjects were aged 18-45 years (including boundary values), male and female. Weight ≥50kg (male) or ≥45kg (female), and body mass index (BMI) of 19-24kg/m2 (including the boundary values at both ends). Have fully understood this study, voluntarily participated in it, and signed the Informed Consent. Subjects are able to communicate well with researchers and complete the study according to protocol. 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. 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: Positive for hepatitis B surface antigen, hepatitis C antibody, syphilis antibody or HIV antibody. 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. A history of postural hypotension with frequent episodes. A history of frequent nausea or vomiting due to any cause. Any clear history of drug or food allergies, especially allergies to ingredients similar to the drugs in this study. Have special dietary requirements and cannot comply with the uniform diet provided by the clinical research center. Previous drug abuse history or positive urine drug screening during screening period. Smokers who smoked more than 5 cigarettes a day in the 3 months before the test. 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. Excessive consumption of tea, coffee (more than 6 cups) and/or caffeinated beverages (more than 1L) per day. 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. Surgical procedures, transfusions of blood or blood components in the month prior to study screening. Blood loss or donation of more than 400 mL in the 2 months prior to screening. Participated in other clinical studies and took experimental drugs within 3 months prior to study screening. Study participants who had received any medication in the 28 days prior to screening. Pregnant or lactating women or women who have had unprotected sex within 14 days
Facility Information:
Facility Name
The Central South University Xiang Ya Hospital
City
Changsha
Country
China

12. IPD Sharing Statement

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

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