A Dose-escalation Study of AND017 in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: AND017 multiple dose; Drug: Placebo; Drug: AND017 single dose

• Registration Number: NCT04751539
• Lead Sponsor: Kind Pharmaceuticals LLC

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-07-16
• Primary Completion: 2019-02-11
• Study Completion: 2019-02-11
• Study First Submitted: 2021-01-28
• Study First Submitted QC: 2021-02-08
• Study First Posted: 2021-02-12
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-07
• Last Update Posted: 2021-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. BMI within 18.0-30.0 kg/m2 (inclusive)
2. Blood Pressure (BP) and 12-lead electrocardiogram (ECG) showing no clinically significant abnormalities during screening;
3. No clinically significant abnormal values in physical examination, clinical laboratory tests, liver function or kidney function;

Exclusion Criteria

1. 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%);
2. Subjects with Hb: male <120 g/L or >160 g/L, female <110 g/L or >150 g/L;
3. Subjects with any abnormalities of hematology during screening: Mean corpuscular volume (MCV), platelet count, serum iron, ferritin;
4. Subjects with a history of medical treatment or disease likely to increase the risk of bleeding or disturbance of blood coagulation;
5. History of deep vein thrombosis, stoke, transient ischemic attack, pulmonary embolism or other thrombosis-related condition within the last five years;
6. History of myocardial infarction, heart failure or acute coronary syndrome;
7. Evidence of active peptic, duodenal or esophageal ulcer disease at screening;
8. History of pulmonary artery hypertension;
9. History of sensitivity to heparin or heparin-induced thrombocytopenia;
10. Subjects with major illness or surgery within past 3 months prior to screening, or planned surgery during study;
11. Known or suspected history of drug abuse within the past 5 years or presence of drug abuse within 3 months before study;
12. 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.
13. 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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AND017 repeated dose escalation	AND017 multiple dose	Subjects will be administrated with repeated dose of AND017 from 4 mg to 30 mg for 10 consecutive days during Part B.
Placebo	Placebo	Placebo administrated once on Day 1 in Part A or daily from Day 1 to Day 10 in Part B
AND017 single dose escalation	AND017 single dose	Subjects will be administrated with single dose of AND017 capsule from 1 mg to 50 mg during Part A.

Primary Outcome Measures

Name	Time	Method
Safety evaluations	17 Days	Incidents of AE and abnormal laboratory tests

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Scientia Clinical Research; 🇦🇺 Randwick, New South Wales, Australia