A Phase I clinical study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral dose escalation of GS1-144 tablets and the effects of food on the pharmacokinetics of GS1-144 in a Chinese population
The primary purpose of this study is to assess the safety and tolerability of single ascending doses of GS1-144 in healthy participants in Part 1 and assessing the food effect in Part 2,and to assess the safety and tolerability of multiple ascending doses of GS1-144 in healthy postmenopausal female participants in Part 3.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
110
GS1-144 tablet is an NK3R antagonist.
Huashan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
Part 1:Number of Participants With Treatment -Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Number of participants with TEAEs and SAEs will be reported
Time frame: Up to Day 4
Part 2: Number of Participants With Treatment -Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).
Number of participants with TEAEs and SAEs will be reported.
Time frame: Up to Day 9;
Part 3: Number of Participants With TEAEs and SAEs
Number of female post-menopausal participants with TEAEs and SAEs will be reported.
Time frame: Up to Day 12
Part1,Part2 and Part3 AUC0-t- Area Under the Drug Concentration-time Curve From Time 0 to the Last Sample Collection Time t for GS1-144
AUC0-t will be assessed and reported.
Time frame: Part 1 Day 1- pre-dose and up to 72 hour post-dose; Part 2 Days 1 and 6-pre-dose and up to 72 hour post-dose, Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose,
Part 1 , Part2 and Part 3: AUC0-infinity- Area Under the Drug Concentration-time Curve From 0 to Infinity for GS1-144
AUC0-infinity will be assessed and reported.
Time frame: Part 1 Day 1- pre-dose and up to 72 hour post-dose; Part 2 Days 1 and 6-pre-dose and up to 72 hour post-dose, Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose,
Part 1, Part2 and Part 3: Cmax- Maximum Observed Plasma Concentration for GS1-144
Cmax will be assessed and reported.
Time frame: Part 1 Day 1- pre-dose and up to 72 hour post-dose; Part 2 Days 1 and 6-pre-dose and up to 72 hour post-dose, Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose,
Part 1 Part2 and Part 3: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for GS1-144
Tmax will be assessed and reported.
Time frame: Part 1 Day 1- pre-dose and up to 24 hour post-dose; Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
Part 1 Part2 and Part 3:: T1/2- Terminal Half-life for GS1-144
T1/2 will be assessed and reported.
Time frame: Time Frame: Part 1 Day 1- pre-dose and up to 72 hour post-dose; Part 2 Days 1 and 6-pre-dose and up to 72 hour post-dose, Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 1 Part2 and Part 3: CL/F- Apparent Clearance for GS1-144
CL/F will be assessed and reported.
Time frame: Part 1 Day 1- pre-dose and up to 72 hour post-dose; Part 2 Days 1 and 6-pre-dose and up to 72 hour post-dose, Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 1 Part2 and Part 3: Vd/F- Apparent Volume of Distribution for GS1-144
Vd/F will be assessed and reported.
Time frame: Part 1 Day 1- pre-dose and up to 72 hour post-dose; Part 2 Days 1 and 6-pre-dose and up to 72 hour post-dose, Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Cmax,ss- Observed Maximum Concentration at Steady State for GS1-144
Cmax at steady state will be assessed and reported.
Time frame: Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 3: Cmin,ss- Observed Minimum Concentration at Steady State for GS1-144
Cmin at steady state will be assessed and reported.
Time frame: Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 3: Tmax,ss- Time of Cmax at Steady State for GS1-144
Tmax at steady state will be assessed and reported.
Time frame: Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 3: Cavg,ss- Average Concentration at Steady State for GS1-144
Cavg at steady state will be assessed and reported.
Time frame: Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 3: AUC0-τ- Area Under the Drug Concentration-time Curve During the Dosing Interval at Steady State for GS1-144
AUC0-T at steady state will be assessed and reported.
Time frame: Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 3: CLss/F- CL for Bioavailability at Steady State for GS1-144
CL/F at steady state will be assessed and reported.
Time frame: Part 3 Days 1 and 7-pre-dose and up to 30 hour post-dose
Part 3: T1/2,ss- Terminal Half-life at Steady State for GS1-144
T1/2 at steady state will be assessed and reported.
Time frame: Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 3: Accumulation Ratio for GS1-144
Accumulation Ratio will be assessed and reported.
Time frame: Part 3 Days 1 and 7-pre-dose and up to 72 hour post-dose
Part 1: Baseline and placebo-adjusted changes in ∆∆QTc and other ECG parameters after oral administration of GF1-144 in healthy subjects
Time frame: Part 1 Day 1- pre-dose and up to 24 hour post-dose
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