A Study of AK3280 in Chinese Healthy Volunteers

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled, single-center, phase I study to evaluate the safety, tolerability, and pharmacokinetics of AK3280 in healthy Chinese subjects.

Detailed Description
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This phase I study is a randomized, double-blind, placebo-controlled, single-center clinical study in healthy subjects. The objectives of the study are to evaluate the safety, tolerability, and pharmacokinetics of AK3280. Approximately, 36 healthy Chinese subjects will be recruited and randomized to orally receive AK3280 or matching placebo. The total duration of the study will be approximately 25 days for each subject.

Official Title
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A Phase I Study to Evaluate The Safety, Tolerability, and Pharmacokinetics of AK3280 in Chinese Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: AK3280
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are willing to sign and date informed consent forms. Male or female participants between 18 and 45 years of age, inclusive. Have a bodyweight ≥50.0 kg (Male) or ≥45.0 kg (Female), and a body mass index (BMI) between 19.0 and 28.0 kg/m^2, inclusive. Participants are in good health without any significant clinical abnormalities on the basis of medical history related to heart, liver, kidneys, gastrointestinal tracts, or mental, central nervous, and metabolic disorders; physical examination (including vital signs); baseline laboratory test and 12-lead electrocardiogram (ECG) results. Participants (including male participants) who have no pregnancy plan and are willing to use an effective method of contraception during the screening period and for three months thereafter without sperm or egg donation plans. Participants who are capable to communicate with investigators and comply with the study requirements. Exclusion Criteria: Allergic to any of the study drug ingredients or ineligible determined by the investigator due to a history of food or drug allergies. Having an abnormal medical history in terms of clinically significant digestive, urological, neurological, hematological, endocrine, oncological, pulmonary, immunological, cardiovascular, or psychiatric diseases or having histories of use any prescription, over-the-counter, herbs, vitamins, or vaccines within four weeks prior to study drug administration. Intolerant to venipuncture or having difficulty in venous blood collection. Having a personal history of drug and alcohol abuse, use of nicotine-containing products, receiving caffeine-containing drinks, taking grapefruit or food made of it, and medications, food, or beverages such as xanthines that could affect the ADME of study medication. Having clinically significant abnormalities in vital sign measures and lab test results. Female subjects are lactating at screening. Previous participation in any clinical trial within 3 months prior to screening. Inability to meet the study requirements in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK3280 Cohort 1<br>Eligible subjects will be administered a single oral dose of 200 mg AK3280 under fasted conditions on Day 1. A multiple dosing period follows with daily 200 mg AK3280 b.i.d. administered with a concurrent low-fat meal intake from Day 4 to Day 16 and a 200 mg AK3280 q.d. dosing on Day 17. | Drug: AK3280<br>* Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral<br>|
| Experimental: AK3280 Cohort 2<br>The dose level of AK3280 for Cohort 2 will be determined by the SRC (Safety Review Committee) based on the safety and PK data gleaned in Cohort 1. Subjects will receive AK3280 following the same dosing schedule as that in Cohort 1, i. e., a single oral dose of AK3280 under fasted conditions on Day 1, multiple AK3280 b.i.d. administration with a concurrent low-fat meal intake from Day 4 to Day 16, and an AK3280 q.d. dose on Day 17. | Drug: AK3280<br>* Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral<br>|
| Experimental: AK3280 Optional Cohort<br>This is an optional dose cohort that the SRC will determine depending on the results of Cohorts 1 and 2, including the proposed dose level. Potential subjects in this cohort will also follow the same dosing scheme as those for Cohorts 1 and 2. | Drug: AK3280<br>* Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral<br>|
| Placebo Comparator: Control Arm<br>There are placebo controls in each dose cohort to assess the safety profile of the study medication. Subjects will be randomized to receive a placebo simultaneously as those subjects randomized to AK3280. | Drug: Placebo<br>* Active Substance: Placebo, Pharmaceutical Form: Tablet, Route of Administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects with Adverse Events (AEs) | An adverse event can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study medication, whether or not considered related to the study medication in this clinical trial. | From baseline up to approximately 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of AK3280 | The maximum observed plasma concentration of AK3280. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Maximum Observed Plasma Concentration (Cmax) of AK3280 Metabolite | The maximum observed plasma concentration of AK3280 metabolite. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Observed trough plasma concentration at end of dosing interval (Ctrough) of AK3280 | The concentration of AK3280 reached immediately before the next dose administered. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Observed trough plasma concentration at end of dosing interval (Ctrough) of AK3280 Metabolite | The concentration of AK3280 metabolite reached immediately before the next dose administered. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Measure maximum plasma concentration at steady state (Css max) of AK3280 | The maximum concentration of AK3280 reached at steady state. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Measure maximum plasma concentration at steady state (Css max) of AK3280 Metabolite | The maximum concentration of AK3280 metabolite reached at steady state. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Time to Maximum Plasma Concentration (Tmax) of AK3280 | The time of occurrence of Cmax of AK3280 | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Time to Maximum Plasma Concentration (Tmax) of AK3280 Metabolite | The time of occurrence of Cmax of AK3280 metabolite | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of AK3280 | The area under the plasma concentration-time curve from time zero up extrapolated to infinity of AK3280. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of AK3280 Metabolite | The area under the plasma concentration-time curve from time zero up extrapolated to infinity of AK3280 metabolite. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Area under the plasma concentration-time curve from time zero up to 12hrs (AUC 0-12h) of AK3280 | The area under the plasma concentration-time curve from time zero up to the 12hrs analytically quantifiable concentration of AK3280. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8, and 12hours post-dose) | 
| Area under the plasma concentration-time curve from time zero up to 12hrs (AUC 0-12h) of AK3280 Metabolite | The area under the plasma concentration-time curve from time zero up to the 12hrs analytically quantifiable concentration of AK3280 metabolite. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8, and 12hours post-dose) | 
| Terminal Half-Life (t1/2) of AK3280 | The apparent elimination half-life of AK3280. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Terminal Half-Life (t1/2) of AK3280 Metabolite | The apparent elimination half-life of AK3280 metabolite. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Apparent Oral Clearance (CL/F) of AK3280 | The oral clearance of AK3280. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Apparent Oral Clearance (CL/F) of AK3280 Metabolite | The oral clearance of AK3280 metabolite. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Apparent volume of distribution during terminal phase (Vz/F) of AK3280 | The Vz/F of AK3280 will be calculated as CL/λz. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) | 
| Apparent volume of distribution during terminal phase (Vz/F) of AK3280 Metabolite | The Vz/F of AK3280 metabolite will be calculated as CL/λz. | Day1/Day17(pre-dose and 0.5,1,1.5,2,2.5,3,4,6,8,12hours post-dose), Day2/Day18(24hours post-dose), Day3/Day19(48hours post-dose), Day4/Day20(72hours post-dose); and Days6,8,10,14,15,16 (pre-dose) |