A Study of HS-10518 in Healthy Female Participants

Study Overview
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Brief Summary
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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
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This is a double-blind, placebo-controlled, multiple-dose, single-center phase 1 study in Chinese healthy premenopausal females aged 18-45 years with a regular menstrual cycle (26-32 days). The main purpose of the study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HS-10518, a gonadotropin-releasing hormone antagonist. About 48 eligible female subjects will be enrolled. The study contains four cohorts. In each cohort, participants will be randomly assigned to the HS-10518 arm or the placebo arm in a 3:1 ratio. HS-10518/matching placebo will be administered from Day 1 to Day 7. The study duration of each participant is up to  10 weeks.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of HS-10518 in Healthy Adult Premenopausal Females in China

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: HS-10518
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Subject is a healthy premenopausal female aged 18-45 (inclusive) at Screening; Subject has a body weight ≥45kg with a body mass index (BMI) of 18-28 kg/m^2 (inclusive); Subject has a normal menstrual cycle for no less than 2 years (Cycle: 26-32 days, menstrual period: 2-7 days), and have a positive ovulation test in the cycle prior to drug administration; Subject is willing to use highly effective, non-hormone contraceptive methods from signing the consent form until 3 months after the last dose; Subject agrees to draw blood in pre-specified time points throughout the study and to attend the follow-up visit; Subject is able to understand the purpose, process and potential adverse events of the study, and is willing to sign a written informed consent form. Exclusion Criteria: • Subject took caffeine-rich or xanthine-rich food or drink (e.g. coffee, tea, chocolate, cola, etc.), tobacco or alcoholic products within 48 hours prior to drug administration; Subject took any grapefruit, grapefruit juice or other products within 7 days prior to first dose of study drug; Subject has a positive breath alcohol test or a history of alcohol abuse; Subject is a heavy smoker, or smokes ≥5 cigarettes per day, or is not able to cease smoking during the study (including e-cigarette); Subject has a history of drug abuse or a positive urine drug test; Subject is pregnant, breastfeeding or has a positive pregnancy test at Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-10518 Dose 1<br>Dose level 1 of HS-10518, QD, orally, 7 days | Drug: HS-10518<br>* QD, orally for 7 days<br>* Other names: TU2670;|
| Placebo Comparator: Placebo Dose 1<br>Dose level 1 of matching placebo, QD, orally, 7 days | Drug: Placebo<br>* QD, orally for 7 days<br>* Other names: HS-10518 Placebo;|
| Experimental: HS-10518 Dose 2<br>Dose level 2 of HS-10518, QD, orally, 7 days | Drug: HS-10518<br>* QD, orally for 7 days<br>* Other names: TU2670;|
| Placebo Comparator: Placebo Dose 2<br>Dose level 2 of matching placebo, QD, orally, 7 days | Drug: Placebo<br>* QD, orally for 7 days<br>* Other names: HS-10518 Placebo;|
| Experimental: HS-10518 Dose 3<br>Dose level 3 of HS-10518, QD, orally, 7 days | Drug: HS-10518<br>* QD, orally for 7 days<br>* Other names: TU2670;|
| Placebo Comparator: Placebo Dose 3<br>Dose level 3 of matching placebo,QD, orally, 7 days | Drug: Placebo<br>* QD, orally for 7 days<br>* Other names: HS-10518 Placebo;|
| Experimental: HS-10518 Dose 4<br>Dose level 4 of HS-10518, QD, orally, 7 days | Drug: HS-10518<br>* QD, orally for 7 days<br>* Other names: TU2670;|
| Placebo Comparator: Placebo Dose 4<br>Dose level 4 of matching placebo, QD, orally, 7 days | Drug: Placebo<br>* QD, orally for 7 days<br>* Other names: HS-10518 Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AE) as assessed by CTCAE v4.0 | Assessment of safety and tolerability of multiple-dose HS-10518 in healthy female subjects in terms of the frequency, severity and causality of AEs, serious adverse events (SAEs) and AEs leading to study discontinuation. CTCAE v4.0 will be used for classification and severity determination. | From screening to day 16 | 
| Assessment of safety and tolerability of HS-10518 in terms of the frequency, severity and causality of AEs, serious adverse events (SAEs) and AEs leading to study discontinuation. | Incidence of any markedly abnormal standard vital sign measurements is collected throughout study. | From screening to day 16 | 
| Incidence of clinically significant abnormal findings in 12-lead electrocardiogram (ECG) | Incidence of any clinically significant abnormal findings in 12-lead ECG is collected throughout study. | From screening to day 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic (PK) parameter: Maximum plasma concentration (Cmax) | The maximum observed plasma concentration of HS-10518. | Day 1 (after the first dose) and Day 7-10 (after the last dose) | 
| PK parameter :Time of maximum observed plasma concentration (Tmax) | Time of the maximum observed plasma concentration of HS-10518. | Day 1 (after the first dose) and Day 7-10 (after the last dose) | 
| PK parameter: 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. | Day 1 (after the first dose) and Day 7-10 (after the last dose) |