To Evaluate the Impact of Smoking on PK After Single-dose Oral Administration of GS1-144 Tablets .

Official title

A Drug-Drug Interaction Study to Evaluate the Effect of Smoking (CYP1A2 Inducer) on the Pharmacokinetics Following a Single Oral Dose of GS1-144 Tablets in Chinese Healthy Postmenopausal Female Trial Participants

Overview

A Drug-Drug Interaction Study to Evaluate the Effect of Smoking (CYP1A2 Inducer) on the Pharmacokinetics Following a Single Oral Dose of GS1-144 Tablets in Chinese Healthy Postmenopausal Female Trial Participants

Detailed description

This drug-drug interaction study adopts an open-label, parallel design to evaluate the effect of smoking on the PK following a single oral dose of GS1-144 tablets in Chinese healthy postmenopausal female trial participants.

Interventions

• Drug GS1-144 tablets
  All trial participants will receive the investigational drug (GS1-144 tablets) at a dose of 30 mg.

Primary outcome measures

• Primary PK parameters for GS1-144: Cmax. [Time frame: up to 72 hours]
• Primary PK parameters for GS1-144: AUC0-t. [Time frame: up to 72 hours]
• Primary PK parameters for GS1-144: AUC0-∞. [Time frame: up to 72 hours]
• Secondary PK parameters of GS1-144: Tmax. [Time frame: up to 72 hours]
• Secondary PK parameters of GS1-144: elimination rate constant (λz). [Time frame: up to 72 hours]
• Secondary PK parameters of GS1-144: t1/2. [Time frame: up to 72 hoursv]
• Secondary PK parameters of GS1-144:CL/F. [Time frame: up to 72 hours]
• Secondary PK parameters of GS1-144: Vd/F. [Time frame: up to 72 hours]
• Secondary PK parameters of GS1-144: AUC_%Extrap. [Time frame: up to 72 hours]

Secondary outcome measures (8)

• PK parameters of the primary metabolite M1: Cmax. [Time frame: up to 72 hours]
• PK parameters of the primary metabolite M1: AUC0-t. [Time frame: up to 72 hours]
• PK parameters of the primary metabolite M1: AUC0-∞. [Time frame: up to 72 hours]
• :PK parameters of the primary metabolite M1: Tmax. [Time frame: up to 72 hours]
• PK parameters of the primary metabolite M1: λz. [Time frame: up to 72 hours]
• PK parameters of the primary metabolite M1: t1/2. [Time frame: up to 72 hours]
• PK parameters of the primary metabolite M1: AUC_%Extrap. [Time frame: up to 72 hours]
• Adverse events (AEs). [Time frame: up to 72 hours]

Eligibility criteria

Inclusion criteria

1)40 to 65 years of age (inclusive) at the time of signing the informed consent form (ICF).

2)Trial participants are healthy females who meet any of the following criteria during screening:

• Consecutive spontaneous amenorrhea ≥ 12 months.
• Consecutive spontaneous amenorrhea ≥ 6 months but < 12 months, with serum follicle-stimulating hormone (FSH) levels > 40 IU/L.
• ≥ 6 weeks after bilateral oophorectomy.
• History of hysterectomy with preservation of one or both ovaries and FSH levels > 40 IU/L.

3)Body weight ≥ 45 kg, and body mass index (BMI) within the range of 18-28 kg/m2 (inclusive).

4)Able to communicate well with the investigator, understand and comply with all study requirements, voluntarily agree to participate in the trial, and understand and voluntarily sign the ICF.

5)Smoker:smoking ≥ 10 cigarettes per day within 6 months prior to screening, and urinary cotinine level ≥ 1,000 ng/mL at screening. Smokers will be required to continue smoking in designated areas according to their habits during the study.

6)Non-smoker: no smoking within 6 months prior to screening, and urinary cotinine level < 200 ng/mL at screening.

Exclusion criteria

• Known history of hypersensitivity to the investigational drug, any of its excipients, or related formulations; or a history of allergic disorders (including but not limited to asthma, urticaria); or being allergy-prone (e.g., known allergy to two or more substances).
• History or current diagnosis of diseases of the circulatory, digestive, urinary, respiratory, endocrine and metabolic, hematological and lymphatic, immune, psychiatric and neurological, or dermatological systems, and deemed unsuitable for participation by the investigator.
• History of severe infection, serious trauma, or major surgery within 6 months prior to screening, or planning to undergo surgery during the trial.
• Blood donation or blood loss ≥ 400 mL, or receipt of blood transfusion within 3 months prior to screening, or planning to donate blood within 1 month after the end of the trial.
• Use of any prescription medications \[including but not limited to drugs known to alter hepatic enzyme activity (e.g., glucocorticoids, sex hormones, anticonvulsants, cyclosporine)\] within 4 weeks prior to screening, or use of any over-the-counter (OTC) medications (including but not limited to herbal medicines, herbal compound prescriptions, health supplements) or vitamin supplements within 2 weeks prior to screening.
• Trial participants with abnormal findings in physical examination, chest X-ray, abdominal and urinary ultrasound, genital ultrasound, thyroid and parathyroid ultrasound, or laboratory tests at screening, which are deemed unsuitable for participation by the investigator.
• During screening or on D-1, any of the following liver function test results as follows: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 1.5 × upper limit of normal (ULN), or total bilirubin (TBIL) ≥ 1.2 × ULN.
• Abnormal vital signs and deemed unsuitable for participation by the investigator, or systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg during screening.
• Abnormal 12-lead ECG findings and deemed unsuitable for participation by the investigator, or QTcF > 470 ms (Fridericia's formula: QTcF = QT/RR0.33, RR = 60/heart rate) during screening.
• Positive test results for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or Treponema pallidum antibody (TP-Ab) during screening.
• Participation in another clinical trial within 3 months prior to screening (except for trial participants who did not receive any investigational intervention), or current participation in any other clinical trial.
• Current or past history of drug abuse within 1 year, or positive urine multi-drug test panel.
• Positive alcohol breath test or history of excessive alcohol consumption (defined as >14 units of alcohol per week) within 3 months prior to screening (One standard alcohol unit is equivalent to 17.5 mL or 14 g of pure ethanol. Alcohol content is labeled by volume (ABV) for all beverage types. This corresponds approximately to 35 mL of 50% spirits or 350 mL of 5% beer), or unwillingness to abstain from alcohol or any alcohol-containing products during the trial.
• Consumption of food or beverages that may affect drug metabolism (e.g., containing grapefruit, starfruit, or their products) within 48 hours prior to admission.
• Excessive consumption of tea, coffee, or caffeinated beverages (>8 cups per day, 1 cup=250 mL) within 3 months prior to screening; or consumption of any food or beverage containing or metabolized to caffeine or xanthine (e.g., coffee, tea, chocolate, cola) within 24 hours prior to admission.
• Pregnant or lactating women, or those who have a clinically significant positive pregnancy test result.
• Poor venous access, a history of difficult venipuncture, intolerance to venipuncture/intravenous indwelling needle, or needle/blood phobia.
• Other conditions deemed unsuitable by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Shandong First Medical University (Shandong Qianfoshan Ho — Shandong

Identifiers

NCT: NCT07534176 · GenSci074-107

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗