A Phase 1 Clinical Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of GS1-144 Tablets
Overview
- Phase
- Phase 1
- Intervention
- GS1-144
- Conditions
- Vasomotor Symptoms
- Sponsor
- Changchun GeneScience Pharmaceutical Co., Ltd.
- Enrollment
- 86
- Locations
- 1
- Primary Endpoint
- Part 1: Number of Participants With Treatment -Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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 to assess the safety and tolerability of multiple ascending doses of GS1-144 in healthy postmenopausal female participants in Part 2.
Detailed Description
This study will be divided into two sequential parts: Part 1 single ascending dose (SAD), and Part 2 multiple ascending dose (MAD) with the overall design. Part 1 will enroll a total of approximately 46 healthy participants in five cohorts at 5 milligram (mg), 15 mg, 30 mg, 60 mg and 90 mg dose levels. Each cohort will have 2 participants receiving placebo. There is no restriction on the male-to female ratio. Part 2 will be conducted after confirming the safety and tolerability of the -\>30mg dose in Part 1 and will enroll a total of approximately 30 healthy postmenopausal female participants and provisionally consists of three cohorts at 15 mg, 30 mg 60 mg and 120mg dose levels. Each cohort will have 2 participants receiving placebo.
Investigators
Eligibility Criteria
Inclusion Criteria
- •At the time of signing the informed consent form (ICF): Part 1 only: healthy male and female participants aged between 18 and 45 years inclusive; Part 2 only: healthy women aged between 40 and 65 years inclusive who have undergone natural menopause;
- •Body weight \>=50 kilogram (kg) (male), \>=45 kg (female) with a body mass index between 18.0 and 32.0 kilogram per square meter (kg/m\^2) inclusive at screening;
- •Part 1 only: Female participants are eligible to participate if they are not pregnant, not breastfeeding, and highly effective contraception includes placement of an intrauterine device or intrauterine system plus use of a condom;
- •Part 1 only: Male participants must agree to practice true abstinence; be surgically sterilized; or agree to use a condom plus effective contraception for their female partner, if of childbearing potential, from screening and for at least 90 days after dosing and refrain from donating sperm during this period. These contraception requirements do not apply if the male participant is in an exclusively same sex relationship;
- •Able to comprehend the nature of the study and any risks associated with participation and willing to cooperate and comply with protocol restrictions and requirements.
Exclusion Criteria
- •Any known allergy to the components or analogues of the investigational product, or those with an allergic constitution;
- •A history of currently suffering from any other cardiovascular, gastrointestinal, endocrine, hematological, hepatic, immunological, metabolic, urinary, pulmonary, neurological, dermatological, psychiatric, renal and/or other major diseases deemed clinically significant by the investigator;
- •Known/confirmed history of malignancy;
- •A history of epileptic seizure or increased risk of epileptic seizure, or participants with a recent history of head trauma leading to loss of consciousness or concussion;
- •A history of currently suffering from hypothalamic dysfunction;
- •Significant acute/chronic infections within two weeks prior to dosing;
- •Undergone major surgical procedures within six months prior to screening or plan to undergo any surgery during the trial;
- •Participated in other clinical trials within 1 month prior to dosing;
- •Have lost or donated more than 400 mL of blood within 1 month prior to screening;
- •Have taken any prescription/over-the-counter drugs or dietary supplements within 7 days prior to dosing or within 5 halflives of the drug;
Arms & Interventions
Part 1 Single Ascending Dose: Cohorts 1 to 6
Participants will receive GS1-144 5 mg, 15 mg, 30 mg, 60 mg , 90 mg and 120mg tablets once on Day 1 in their respective Cohort in Part 1. 2 participants will receive placebo in each cohort.
Intervention: GS1-144
Part 1 Single Ascending Dose: Cohorts 1 to 6
Participants will receive GS1-144 5 mg, 15 mg, 30 mg, 60 mg , 90 mg and 120mg tablets once on Day 1 in their respective Cohort in Part 1. 2 participants will receive placebo in each cohort.
Intervention: Placebo
Part 2 Multiple Ascending Dose: Cohorts 1 to 4
tablets once on Day 1 in their respective Cohort in Part 2. 2 participants will receive placebo in each cohort.
Intervention: GS1-144
Part 2 Multiple Ascending Dose: Cohorts 1 to 4
tablets once on Day 1 in their respective Cohort in Part 2. 2 participants will receive placebo in each cohort.
Intervention: Placebo
Outcomes
Primary Outcomes
Part 1: Number of Participants With Treatment -Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Day 4
Number of participants with TEAEs and SAEs will be reported.
Part 2:Number of Participants With TEAEs and SAEs
Time Frame: Up to Day 12
Number of female post-menopausal participants with TEAEs and SAEs will be reported.
Secondary Outcomes
- Parts 1 and 2: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for GS1-144(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)
- Parts 1 and 2: Vd/F- Apparent Volume of Distribution for GS1-144(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)
- Parts 1 and 2: T1/2- Terminal Half-life for GS1-144(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 2: Cavg,ss- Average Concentration at Steady State for GS1-144(Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose)
- Part 2: AUC0-τ- Area Under the Drug Concentration-time Curve During the Dosing Interval at Steady State for GS1-144(Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose)
- Parts 1 and 2: CL/F- Apparent Clearance for GS1-144(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 2: Cmin,ss- Observed Minimum Concentration at Steady State for GS1-144(Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose)
- Part 2: Tmax,ss- Time of Cmax at Steady State for GS1-144(Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose)
- Part 2: CLss/F- CL for Bioavailability at Steady State for GS1-144(Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose)
- Part 2: T1/2,ss- Terminal Half-life at Steady State for GS1-144(Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose)
- Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose(Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose)
- Parts 1 and 2: Cmax- Maximum Observed Plasma Concentration for GS1-144(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)
- Parts 1 and 2: AUC0-t- Area Under the Drug Concentration-time Curve From Time 0 to the Last Sample Collection Time t for GS1-144(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)
- Parts 1 and 2: AUC0-infinity- Area Under the Drug Concentration-time Curve From 0 to Infinity for GS1-144(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 2: Cmax,ss- Observed Maximum Concentration at Steady State for GS1-144(Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose)