A Dose-escalation Study of AND017 in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
This is a phase I, randomized, double-blind, placebo-controlled, dose-escalation study in healthy subjects to evaluate safety, tolerability, PKs and PDs of AND017 following oral single and multiple dose administration.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Dose-Escalation Study in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AND017 Following Oral Single and Multiple Dose Administration

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: AND017 single dose
* Drug: AND017 multiple dose
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BMI within 18.0-30.0 kg/m2 (inclusive) Blood Pressure (BP) and 12-lead electrocardiogram (ECG) showing no clinically significant abnormalities during screening; No clinically significant abnormal values in physical examination, clinical laboratory tests, liver function or kidney function; Exclusion Criteria: Current or chronic history of liver disease or known hepatic or biliary abnormalities, including but not limited to ALT, alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%); Subjects with Hb: male <120 g/L or >160 g/L, female <110 g/L or >150 g/L; Subjects with any abnormalities of hematology during screening: Mean corpuscular volume (MCV), platelet count, serum iron, ferritin; Subjects with a history of medical treatment or disease likely to increase the risk of bleeding or disturbance of blood coagulation; History of deep vein thrombosis, stoke, transient ischemic attack, pulmonary embolism or other thrombosis-related condition within the last five years; History of myocardial infarction, heart failure or acute coronary syndrome; Evidence of active peptic, duodenal or esophageal ulcer disease at screening; History of pulmonary artery hypertension; History of sensitivity to heparin or heparin-induced thrombocytopenia; Subjects with major illness or surgery within past 3 months prior to screening, or planned surgery during study; Known or suspected history of drug abuse within the past 5 years or presence of drug abuse within 3 months before study; Donated blood >400 mL or significant blood loss equivalent to 400 mL or received blood transfusion within 3months of screening; or donated blood >200 mL or significant blood loss equivalent to 200 mL within 1 month prior to screening. Participation in any clinical study with an investigational drug, biologic or device within 4 weeks or 5 times the half-life of the specific drug/biologics (whichever is longer), prior to dosing;

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AND017 single dose escalation<br>Subjects will be administrated with single dose of AND017 capsule from 1 mg to 50 mg during Part A. | Drug: AND017 single dose<br>* AND017 administrated as oral single-dose on Day 1 in Part A<br>|
| Placebo Comparator: AND017 repeated dose escalation<br>Subjects will be administrated with repeated dose of AND017 from 4 mg to 30 mg for 10 consecutive days during Part B. | Drug: AND017 multiple dose<br>* AND017 administrated once daily from Day 1 to Day 10 in Part B<br>|
| Placebo Comparator: Placebo<br>Placebo administrated once on Day 1 in Part A or daily from Day 1 to Day 10 in Part B | Drug: Placebo<br>* Placebo administrated once on Day 1 in Part A or daily from Day 1 to Day 10 in Part B<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluations | Incidents of AE and abnormal laboratory tests | 17 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Cmax of AND017 | The plasma Cmax of AND017 by single dose administration | 1 day | 
| Plasma Tmax of AND017 | The plasma Tmax of AND017 after single dose administration on D1 and multiple doses for 10 consecutive days on D10 | 1 day and 10 days | 
| Plasma t1/2 of AND017 | The plasma T1/2 of AND017 after single dose administration on D1 and multiple doses for 10 consecutive days on D10 | 1 day and 10 days | 
| Plasma AUC of AND017 | The plasma AUCs of AND017 after single dose administration on D1 and multiple doses for 10 consecutive days on D10 | 1 day and 10 days | 
| Plasma CL/F of AND017 | The plasma CL/F of AND017 after single dose administration | 1 day | 
| Plasma Vz/F of AND017 | The plasma Vz/F of AND017 after single dose administration | 1 day | 
| Plasma MRT of AND017 | The plasma MRT of AND017 after single dose administration | 1 day | 
| Plasma λz of AND017 | The plasma λz of AND017 after single dose administration | 1 day | 
| Plasma %AUCex of AND017 | The plasma %AUCex of AND017 after single dose administration | 1 day | 
| Plasma Css,min of AND017 | The plasma Css,min of AND017 by multiple administration for 10 consecutive days | 10 days | 
| Plasma Css,max of AND017 | The plasma Css,max of AND017 by multiple administration for 10 consecutive days | 10 days | 
| Plasma Css,avg of AND017 | The plasma Css,avg of AND017 by multiple administration for 10 consecutive days | 10 days | 
| Plasma CLss/F of AND017 | The plasma CLss/F of AND017 by multiple administration for 10 consecutive days | 10 days | 
| Plasma Vss/F of AND017 | The plasma Vss/F of AND017 by multiple administration for 10 consecutive days | 10 days | 
| Plasma Rac(AUC) of AND017 | The plasma Rac(AUC) of AND017 by multiple administration for 10 consecutive days | 10 days | 
| Plasma DF of AND017 | The plasma DF of AND017 by multiple administration for 10 consecutive days | 10 days | 
| PD parameters | Change from baseline levels of EPO | 17 days | 
| PD parameters | Change from baseline levels of HB | 17 days | 
| PD parameters | Change from baseline levels of RET | 17 days |