A Phase 1, Open Label, Randomized, Multiple Ascending Dose (MAD) Study Evaluating the Safety, Tolerability and Pharmacokinetics of KSHN001034 in Healthy Postmenopausal Female Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Safety and tolerability of KSHN001034 as assessed by number of participants with Seriou Adverse Events (SAEs), Adverse Events (AEs) resulting in trial discontinuation, severity (by NCI CTCAE v5.0) and causality across test and reference arms
研究概览
简要总结
This is a Phase 1, open-label, randomized, multiple ascending dose (MAD) study designed to evaluate the safety, tolerability, and pharmacokinetics of KSHN001034, an investigational drug intended as a fulvestrant equivalent, in healthy postmenopausal female volunteers. Approximately 40 participants will be enrolled across five cohorts, each receiving ascending intramuscular (IM) or subcutaneous (SC) doses of KSHN001034 (equivalent to 100 mg, 200 mg, or 300 mg fulvestrant) administered once weekly (Q7D) on Days 1, 8, 15, and 22. A comparator arm using 500 mg fulvestrant IM on Days 1 and 15 is included in each cohort. Safety assessments, including adverse event monitoring and laboratory evaluations, will be conducted from baseline through the end-of-study visit on Day 36. Pharmacokinetic sampling will occur throughout the dosing period and at follow-up to evaluate key PK parameters such as Cmax, Cmin, Tmax, AUC, and half-life. The study aims to determine the tolerability profile and PK characteristics of KSHN001034 to support further clinical development.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 45.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- Female
入选标准
- •Able to provide written Informed Consent and communicate with the investigator and comprehend study-related procedures.
- •Healthy, postmenopausal females aged 45 to 60 years old (inclusive), as determined by medical history and physical examination.
- •Body Mass Index at screening between 18 and 30 kg/m2, inclusive.
- •Post-menopausal females (Menopause is defined as the female is either 12 months off menstrual period after the age of 50 years, or 12 months off menstrual period Ater the age of 45 years and FSH greater than 40 mIU/mL
- •Note: Amenorrhea should not be due to lactation).
- •Participant must be healthy on the basis of their medical history, a physical examination, vital signs, and 12-lead Electrocardiogram (ECG) performed during screening and as determined by the Principal Investigator (PI).
- •Hemoglobin at screening and Day (-1) should be greater than or equal to 11 g/dL
- •Ability to communicate well and to comply with the requirements of the entire study.
- •Adequate venous access and can able to give required blood samples.
排除标准
- •History or presence of cardiovascular, pulmonary, hepatic, renal, hematologic, coagulation, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease or any other clinical significant abnormalities during screening investigations which, in the opinion of the PI, may either put the participant at risk because of participation in the study, or influence the results or the participants ability to participate in the study.
- •Evidence of organ dysfunction [e.g. liver dysfunction; greater than or equal to Upper Limit of Normal (ULN) for ALT, AST or ALP or renal dysfunction (less than 90 mL/min of creatinine clearance by Cockroft-Gault formula] or any clinically significant abnormalities in other clinical laboratory parameters at screening as determined by the investigator.
- •QTc (Bazzett) interval greater than or equal to 450 ms on ECG at screening.
- •Any major surgery requiring general anesthesia within 3 months prior to screening.
- •Known or suspected history of alcohol dependency or addictive substance use, as judged by the investigator Note: Participants will be required to abstain from recreational use of soft addictive substances (such as marijuana) within 2 weeks or hard addictive substances (such as cocaine, phencyclidine, crack, opioid derivatives including heroin, and amphetamine derivatives) within 2 months prior to screening
- •History or presence of malignancy in the last 5 years
- •Positive testing for human immunodeficiency virus (HIV I or II), hepatitis B (hepatitis B surface antigen [HBsAg]), or hepatitis C (Anti-HCV antibody) at screening.
- •Received or intending to receive a vaccination in the two weeks prior to dosing, or anytime during study participation.
- •Donated blood within 60 days of screening or otherwise experienced blood loss of greater than 250 mL within the same period.
- •Presence of low platelet count (i.e. lower than LLN), bleeding issues or family history of bleeding disorders.
- •Participant has a history of hypersensitivity to heparin as checked at screening.
- •History of hypersensitivity or idiosyncratic reaction to test drug or any drug chemically similar to the drug under investigation or any of the excipients.
- •The participant has any estrogen- dependent conditions including benign breast conditions
- •The participant has a history of osteoporosis or any disease affecting bone or steroid etabolism.
- •Intolerance to/ fear of venipuncture, needles, or blood draws.
- •Positive serum pregnancy test during screening or Lactating mothers
- •Has received another new chemical entity/investigational drug within 28 days or 5 half-lives of investigational drug (whichever is longer) of the first administration of investigational product in this study.
- •Use of any prescribed or non-prescribed medication, herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of investigational product
- •The participant has consumed grapefruit-containing beverages and foods 7 days prior to dosing.
结局指标
主要结局
Safety and tolerability of KSHN001034 as assessed by number of participants with Seriou Adverse Events (SAEs), Adverse Events (AEs) resulting in trial discontinuation, severity (by NCI CTCAE v5.0) and causality across test and reference arms
时间窗: Safety and tolerability of KSHN001034 as assessed by number of participants with Seriou Adverse Events (SAEs), Adverse Events (AEs) resulting in trial discontinuation, severity (by NCI CTCAE v5.0) and causality across test and reference arms
次要结局
- PK parameters including but not limited to Cmax, Cmin, Tmax, AUClast, AUC0-tau, Tlast, Clast, T1/2 and MRT.(Up to Day 36)
研究者
Dr Pawan Singh
Kashiv Biosciences LLC