A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TRT-448 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 144
- 主要终点
- Safety and tolerability of TRT-448 in healthy participants
研究概览
简要总结
Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TRT-448 in Healthy Adult Subjects
详细描述
This is a randomized, double-blind, placebo-controlled first-in-human (FIH) study of TRT-448 conducted in healthy adult participants. Key safety and tolerability assessments of TRT-448 will be regularly reviewed by an appointed Safety Review Committee (SRC). The study will be conducted in 2 parts: single ascending dose (SAD) and multiple ascending dose (MAD) healthy adult subject cohorts. Eligible subjects will be enrolled into a SAD cohort and will be randomized to receive a single dose of TRT-448 or placebo in a 3:1 ratio, respectively, via oral administration. Eligible participants will be enrolled into MAD cohorts and randomized to receive TRT-448 or placebo in a 3:1 ratio, respectively, once daily (QD) via oral administration from Day 1 and through Day 14 (MAD escalation cohorts) or from Day 1 through Day 28 (MAD expansion cohorts), inclusive. A total of up to 144 participants are planned to be enrolled. Each subject will be assessed for safety, pharmacokinetics and pharmacodynamics of TRT-448.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Medically healthy , as determined by pre-study medical history, and without clinically significant abnormalities
- •Adult males and females, 18 to 55 years of age (inclusive) at screening
- •Body mass index (BMI) between 18 and 32 kg/m2 (inclusive) with body weight: ≥ 70 kg for the SAD 1 cohort; ≥ 50 kg for all other cohorts
- •Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions
排除标准
- •History of anaphylaxis or other significant allergy which would interfere with the volunteer's ability to participate in the study, including severe Types I-IV hypersensitivity reactions, cytokine release syndrome, or allergic reactions to multiple drugs
- •History or presence of cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal cholecystectomy, irritable bowel syndrome, inflammatory bowel disease, etc.), esophageal, endocrine, immunologic, autoimmune and/or inflammatory disease, dermatologic, psychiatric, or neurological disease/disorder
- •History of surgery or hospitalization within 3 months prior to screening, or surgery planned during the study.
- •Any history of malignant disease in the last 10 years, including leukemia, lymphoma or any significant hematology/oncology disease.
- •Note: Participants with curatively resected non-melanoma skin cancers >2 years prior to screening or curatively excised cervical carcinoma in situ > 5 years prior to screening are not excluded.
- •Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
- •History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death or screening QTcF > 450 msec in males or > 470 msec in female) or a known arrhythmia (Note: asymptomatic first-degree heart block is not exclusionary).
- •Presence or having sequelae of gastrointestinal, liver (including Gilbert's syndrome), kidney, gallbladder, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- •Liver function test results elevated more than 1.3-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT).
- •Estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73m2 using the 2021 CKD-EPI creatinine equation.
- •Positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
研究组 & 干预措施
TRT-448
TRT-448 dosed as oral capsules once (in single ascending dose cohorts) and daily for up to 28 days (in multiple ascending dose cohorts)
干预措施: TRT-448 (Drug)
Placebo
Placebo dosed as oral capsules once (in single ascending dose cohorts) and once daily for up to 28 days (in multiple ascending dose cohorts)
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and tolerability of TRT-448 in healthy participants
时间窗: Day 1 to Day 28
Incidence of treatment-emergent adverse events
次要结局
- t1/2(Day 1 to Day 28)
- Cmax(Day 1 to Day 28)
- Tmax(Day 1 to Day 28)
- AUClast(Day 1 to Day 28)