A Randomized, Placebo Controlled, Subject and Investigator Blinded, first-in- Human, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics After Intra-articular Injection of LRX712 Into the Knee of Osteoarthritic Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single intra-articular (i.a.) injection in Osteoarthritic (OA) patients
研究概览
简要总结
This study is designed to evaluate, for the first time in humans, safety and tolerability of single ascending doses of intra-articular (i.a.) injections of LRX712 into the knee of patients with moderate osteoarthritis (OA), in order to support the further clinical development. This study will also allow establishment of the systemic and local pharmacokinetics (PK) of LRX712 and the exploration of biomarkers of cartilage breakdown and regeneration in OA patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients, 30 to 65 years of age inclusive, and in good health as determined by medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- •At screening, and at baseline vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three minutes, and again (when required) after three minutes in the standing position as outlined in the SOM.
- •Sitting vital signs should be guided by the following ranges:
- •body temperature between 35.0-37.5 °C
- •systolic blood pressure 90-139 mm Hg
- •diastolic blood pressure 50-89 mm Hg
- •pulse rate, 40 - 90 bpm • Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 32 kg/m
- •BMI = Body weight (kg) / [Height (m)]
排除标准
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
- •Pregnant or nursing (lactating) women
- •Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
- •A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening and baseline
- •PR > 200 msec
- •QRS complex > 120 msec
- •QTcF > 450 msec (males)
- •QTcF > 460 msec (females)
- •Known family history or known presence of long QT syndrome
研究组 & 干预措施
LRX712
LRX712 given intra-articularly
干预措施: LRX712 (Drug)
Placebo
Placebo given intra-articularly
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single intra-articular (i.a.) injection in Osteoarthritic (OA) patients
时间窗: Day 29
To evaluate Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single i.a. injection in osteoarthritic patients
次要结局
- CL/F - Total clearance(pre-dose to 29 days post-dose)
- Time to Reach the Maximum Plasma Concentration (Tmax)(pre-dose to 29 days post-dose)
- Maximum Observed Plasma Concentration (Cmax)(pre-dose to 29 days post-dose)
- Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast)(pre-dose to 29 days post-dose)
- Half-life (T1/2)(pre-dose to 29 days post-dose)
- Area under the plasma concentration-time curve from time zero to infinity (AUCinf)(pre-dose to 29 days post-dose)
- Vz/F - Volume of Distribution(pre-dose to 29 days post-dose)