Safety, Tolerability and Pharmacokinetics of AD16 Tablets in Adult Healthy Subjects After Single Administration (AD16)

The primary objective of this study was to evaluate the safety, tolerability and pharmacokinetic characteristics of single administration of AD16 tablets in healthy adults under fasting conditions, and the secondary objective was to preliminarily evaluate the material balance of single administration of AD16 tablets in fasting conditions.

The study is divided into two parts: preliminary test and formal test. The formal trial was a single-center, randomized, placebo-controlled, double-blind, dose-increasing study, with 5 dose groups (5mg, 10mg, 20mg, 30mg and 40mg, respectively).

Ten subjects (male and female) were enrolled in each dose group, of which 8 received the experimental drug and 2 received placebo.

Urine and fecal samples were collected in the 20mg dose group for material balance study.Urine and fecal samples were collected in the 20mg dose group for material balance study.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: AD16 5mg、10mg、20mg、30mg、40mg、60mg、80mg; Drug: AD16 placebo 5mg、10mg、20mg、30mg、40mg、60mg、80mg

• Study Type: Interventional
• Enrollment (Actual): 70
• 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. Surgical procedures, transfusions of blood or blood components in the month prior to study screening.
12. Blood loss or donation of more than 400 mL in the 2 months prior to screening.
13. Participated in other clinical studies and took experimental drugs within 3 months prior to study screening.
14. Study participants who had received any medication in the 28 days prior to screening.
15. Pregnant or lactating women or women who have had unprotected sex within 14 days.
16. Those unable to complete the study for other reasons or deemed unsuitable for inclusion by the researcher.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AD16; The experimental group received AD16, which was a tablet with a dosage form of 10mg/tablet. Take warm water orally on an empty stomach in the morning, once a day.7 dosing cohorts will receive a single oral dose of AD16.	Drug: AD16 5mg、10mg、20mg、30mg、40mg、60mg、80mg; Take one AD16 tablet in the morning
Placebo Comparator: placebo; The placebo group received AD16 placebo, which was a tablet with a dosage form of 10mg/tablet. Take warm water orally on an empty stomach in the morning, once a day. 7 dosing cohorts will receive a single oral dose of AD16 placebo.	Drug: AD16 placebo 5mg、10mg、20mg、30mg、40mg、60mg、80mg; Participants will take a placebo pill matching AD16 once in the morning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	The number of adverse events	day-7 to day3
Serious adverse events	The number of serious adverse events	day-7 to day3
Number of participants with abnormal laboratory test results	Laboratory tests include Blood routine, blood biochemistry, coagulation function and urine routine	Screening period (day-7 to day-2) and day3
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.	day-7 to day3
Number of participants with abnormal 12-lead electrocardiogram readings	abnormal 12-lead electrocardiogram readings	Screening period (day-7 to day-2) and day3
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) and day3
Concomitant Medication	Any concomitant medication	up to day3
Tmax of AD16	Time to reach the maximum (peak) plasma concentration following drug administration	day1 to day3
Cmax of AD16	Maximum (peak) plasma drug concentration	day1 to day3
t1/2z of AD16	Elimination half-life (to be used in a one-compartment or noncompartmental model)	day1 to day3
AUC 0-∞ of AD16	AUC 0-∞ is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time). area under curve(AUC)	day1 to day3
AUC 0-t of AD16	AUC 0-t is defined as the concentration of drug from time zero to the last quantifiable concentration.area under curve(AUC)	day1 to day3
CL/F of AD16	CL/F is defined as the ratio of total clearance(CL) to bioavailability(F). administration	day1 to day3
Vd/F of AD16	Apparent volume of distribution after non-intravenous administration	day1 to day3
λz of AD16	Terminal disposition rate constant/terminal rate constant	day1 to day3
Mean retention time（MRT ）of AD16	Mean retention time from first dosing to t hours or mean retention time from first dosing to infinity	day1 to day3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ae	The amount of drug excreted in urine at t hours after administration The amount of drug excreted by fecal sample at t hours after administration	day-3 to day3
Fe0-t	Cumulative excretion rate of drugs through urine Cumulative rate of drug excretion through feces	day-3 to day3
Renal clearance	Renal clearance of drug from plasma	day-3 to day3

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): January 30, 2019
• Primary Completion (Actual): May 31, 2020
• Study Completion (Actual): May 31, 2020

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 28, 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-AD16-2018-01

Drug and device information, study documents

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