Clinical trial NCT06204250: A Study to Assess Safety and Tolerability of GS1-144 in Healthy Volunteers
Official title: A Phase 1 Clinical Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of GS1-144 Tablets
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Vasomotor Symptoms
Adult Healthy Volunteers
Lead sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2024-01-12
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria:

1. 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;
2. 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;
3. 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;
4. 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;
5. 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:

1. Any known allergy to the components or analogues of the investigational product, or those with an allergic constitution;
2. 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;
3. Known/confirmed history of malignancy;
4. 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;
5. A history of currently suffering from hypothalamic dysfunction;
6. Significant acute/chronic infections within two weeks prior to dosing;
7. Undergone major surgical procedures within six months prior to screening or plan to undergo any surgery during the trial;
8. Participated in other clinical trials within 1 month prior to dosing;
9. Have lost or donated more than 400 mL of blood within 1 month prior to screening;
10. Have taken any prescription/over-the-counter drugs or dietary supplements within 7 days prior to dosing or within 5 halflives of the drug;
11. Clinically significant abnormalities on physical examination or genitourinary ultrasound at the time of screening;
12. Clinically significant abnormalities in vital signs;
13. Prolonged QTcF interval in 12-lead ECG results ;
14. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), blood creatinine (CRE), blood urea nitrogen (BUN), or international normalized ratio (INR) higher than the upper limit of normal (ULN) at screening, that are considered as clinically significant abnormalities by the investigator;
15. Part 2 only: abnormal sex hormone levels at screening that are considered clinically significant by the investigator;
16. Clinically significant abnormalities in thyroid function, parathyroid function, and neck ultrasound results at screening;
17. Women with positive pregnancy test result or those who are breastfeeding before dosing;
18. Positive hepatitis C virus antibody (HCV Ab), positive human immunodeficiency virus antibody (HIV Ab) or positive hepatitis B surface antigen (HbsAg) result at screening;
19. Unable to refrain from consuming grapefruit, pomelo, grapefruit juice, or pomelo juice from 48 hours prior to check-in until the end of the study;
20. Unable to refrain from consuming any foods or beverages containing caffeine or xanthine from 48 hours prior to check-in until the end of the study;
21. Unable to abstain from smoking/using tobacco products from 48 hours prior to check-in until the end of the study;
22. Unable to refrain from consuming alcohol from 48 hours prior to check-in until the end of the study;
23. Any history of narcotic use or drug abuse;
24. Any medical or other condition may affect the clinical trial.

Primary outcomes:
measure: Part 1: Number of Participants With Treatment -Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 4
measure: Part 2:Number of Participants With TEAEs and SAEs
timeFrame: Up to Day 12
Secondary outcomes:
measure: 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
timeFrame: 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
measure: Parts 1 and 2: AUC0-infinity- Area Under the Drug Concentration-time Curve From 0 to Infinity for GS1-144
timeFrame: 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
measure: Parts 1 and 2: Cmax- Maximum Observed Plasma Concentration for GS1-144
timeFrame: 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
measure: Parts 1 and 2: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for GS1-144
timeFrame: 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
measure: Parts 1 and 2: T1/2- Terminal Half-life for GS1-144
timeFrame: 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
measure: Parts 1 and 2: CL/F- Apparent Clearance for GS1-144
timeFrame: 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
measure: Parts 1 and 2: Vd/F- Apparent Volume of Distribution for GS1-144
timeFrame: 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
measure: Part 2: Cmax,ss- Observed Maximum Concentration at Steady State for GS1-144
timeFrame: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
measure: Part 2: Cmin,ss- Observed Minimum Concentration at Steady State for GS1-144
timeFrame: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
measure: Part 2: Tmax,ss- Time of Cmax at Steady State for GS1-144
timeFrame: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
measure: Part 2: Cavg,ss- Average Concentration at Steady State for GS1-144
timeFrame: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
measure: Part 2: AUC0-τ- Area Under the Drug Concentration-time Curve During the Dosing Interval at Steady State for GS1-144
timeFrame: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
measure: Part 2: CLss/F- CL for Bioavailability at Steady State for GS1-144
timeFrame: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
measure: Part 2: T1/2,ss- Terminal Half-life at Steady State for GS1-144
timeFrame: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
measure: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
timeFrame: Part 2 Days 1 and 7-pre-dose and up to 30 hour post-dose
Other outcomes:
Locations:
city: Perth
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
References: