A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HS-10518 in Healthy Adult Premenopausal Females in China
Overview
- Phase
- Phase 1
- Intervention
- HS-10518
- Conditions
- Not specified
- Sponsor
- West China Second University Hospital
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Incidence of Adverse Events (AE) as assessed by CTCAE v4.0
- Status
- Completed
- Last Updated
- last month
Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HS-10518 in healthy adult premenopausal females in China
Detailed Description
In this randomized, double-blind, placebo-controlled Phase I clinical trial, 60 participants were randomized in a 1:1:1:1:1:1 ratio to receive HS-10518 (10 mg Q12h, 20 mg QD, 20 mg Q12h, 40 mg QD, or 80 mg QD) or placebo for 14 consecutive days. Assessments included safety, tolerability, PK parameters, and PD parameters.
Investigators
Yu Qin
Director, Office of Clinical Trial Institution
West China Second University Hospital
Eligibility Criteria
Inclusion Criteria
- •Subjects may be enrolled only if they meet all the following criteria:
- •At the time of signing the informed consent form, the subject must be 18 to 40 years old (inclusive).
- •Confirmed to be a healthy subject through medical assessment, including indicators such as medical history, physical examination, laboratory tests, and 12-lead electrocardiogram (ECG).
- •Regular menstrual cycles for at least 6 months prior to screening, with:
- •Cycle length: 24 to 32 days;
- •Menstrual period duration: 2 to 7 days;(The first day of menstruation is defined as Day 1 of the menstrual cycle.)
- •Baseline sex hormone levels meet the following requirements: Follicle-Stimulating Hormone (FSH) \< 10 IU/L and Estradiol (E2) \< 100 pg/mL; in addition, other sex hormone indicators must be assessed by the investigator as normal for the subject to be randomly enrolled.
- •Body weight ≥ 45 kg, and Body Mass Index (BMI) within the range of 18 to 28 kg/m² (inclusive).
- •The subject agrees to use highly effective non-hormonal contraceptive methods from the date of signing the informed consent form until 3 months after the administration of the last dose of the study drug. Highly effective non-hormonal contraceptive methods include:
- •Continuous abstinence;
Exclusion Criteria
- •Subjects will be excluded from the study if they meet any one of the following criteria:
- •Has a history of abnormal uterine bleeding within 3 months prior to screening.
- •Has never been sexually active.
- •Has consumed foods or beverages rich in caffeine and/or xanthine (e.g., coffee, tea, chocolate, caffeinated carbonated beverages such as cola), tobacco-containing products (e.g., cigarettes), alcohol, or alcohol-containing products within 48 hours prior to drug administration.
- •Has consumed grapefruit, grapefruit juice, bitter orange, bitter orange marmalade, bitter orange juice, or other products containing grapefruit or bitter orange within 7 days prior to the first dose.
- •Has a history of smoking or alcohol abuse within 6 months prior to screening:
- •Smoking: More than 5 cigarettes per day or equivalent tobacco products;
- •Alcohol abuse: Alcohol consumption of ≥14 units per week (1 unit = 285 mL of beer, 25 mL of spirits with alcohol content ≥40%, or 150 mL of wine).
- •Is suspected of substance abuse involving barbiturates, amphetamines, benzodiazepines, cocaine, opioids, cannabis, methadone, phencyclidine (PCP), tricyclic antidepressants (TCAs), or methamphetamine.
- •Has a positive alcohol breath test or positive urine drug abuse screening result.
Arms & Interventions
HS-10518 Dose 1
Dose level 1 of HS-10518, 10 mg Q12h, orally, 14 days
Intervention: HS-10518
HS-10518 Dose 2
Dose leve2 of HS-10518, 20 mg QD, orally, 14 days
Intervention: HS-10518
HS-10518 Dose 3
Dose leve3 of HS-10518, 20 mg Q12h, orally, 14 days
Intervention: HS-10518
HS-10518 Dose 4
Dose leve4 of HS-10518, 40 mg QD, orally, 14 days
Intervention: HS-10518
HS-10518 Dose 5
Dose leve5 of HS-10518, 80 mg QD, orally, 14 days
Intervention: HS-10518
Placebo
placebo, BID, orally, 14 days
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of Adverse Events (AE) as assessed by CTCAE v4.0
Time Frame: From screening to day 21
Assessment of safety and tolerability of multiple-dose HS- 10518 in healthy female participants in terms of the frequency, severity and causality of AEs, serious adverse events (SAEs) and AEs leading to study discontinuation.
Number of Participants with Clinically Significant Changes in Laboratory Parameters
Time Frame: From screening to day 16
Laboratory parameters include hematology, clinical chemistry, and urinalysis. The number and percentage of participants with clinically significant changes
Incidence of clinically significan t abnormal findings in 12-lead electrocar
Time Frame: From screening to day 16
Incidence of any clinically significant abnormal findings in 12-lead ECG is collected throughout study
Secondary Outcomes
- Maximum plasma concentration (Cmax)(From screening to day 16)
- Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t)(Area under the concentration-time curve from time 0 to the last quantifiable concentration of HS-10518)
- Time of the maximum observed plasma concentration(From screening to day 16)