A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Doses of KSP-1007 Alone and Coadministered With Meropenem in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 123
- 试验地点
- 1
- 主要终点
- Incidence of adverse events assessed by subject .
研究概览
简要总结
This study is a first-in-human, Phase 1, randomized, double- blind, four-part, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of single (Part 1) and repeat (Part 2) escalating intravenous doses of KSP-1007. Repeated escalating doses of KSP-1007 will be co-administered with meropenem (Part 3) and single, ascending doses of KSP-1007 will be administered alone in healthy Japanese subjects (Part 4)
详细描述
Carbapenem-resistant Gram-negative bacteria are responsible for serious, life-threatening infections and are regarded as an urgent threat by the Centers for Disease Control and Prevention and the World Health Organizations. One principal mechanism of carbapenem resistance is bacterial production of carbapenemases, which reduce the effectiveness of meropenem and other carbapenem class antibiotics. Sumitovant Biopharma is developing a fixed combination of meropenem and KSP-1007 for the treatment of serious bacterial infections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, 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
- •Healthy male or female subjects 18 to 55 years of age, inclusive
- •Females that engage in heterosexual activity must agree to use a highly selective birth control (BC) method (< 1% failure rate per year) throughout the study, or have a documented reproductive status of non-childbearing based on medical history, or is postmenopausal
- •Males that engage in heterosexual activity that has the risk of pregnancy must agree to use effective BC and agree to not donate sperm during the study and for at least 90 days after the last dose of the study medication
- •Body mass index (BMI) 2: 18 kg/m2 and :s 32 kg/m2
排除标准
- •History of Gilbert's Syndrome
- •History of severe allergic reactions to β-lactams or β-lactamase inhibitors or a history allergic reactions to multiple medications.
- •Pregnant female, determined by positive serum or urine human chorionic gonadotropin pregnancy test at Screening, or prior to dosing
- •Lactating female
- •Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at Screening) of > 499 mL within 56 days prior to Day 1
- •Participation in a study with an investigational drug or device study with last dose of investigational drug within 30 days (90 days if the study involved a biologic, cellular, or vaccine product) or 5 half-lives, whichever is longer, before study treatment administration
- •Subjects with abnormal hepatic and/or renal function, that could interfere with the metabolism, and/or excretion of the study treatments
- •Abnormal blood pressure, either low (defined as < 90 mmHg systolic and/ or < 45 mmHg diastolic) or high (defined as > 140 mmHg systolic and/ or > 90 mmHg diastolic) at Screening
- •Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV at Screening. Subjects who test positive for hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) also will be ineligible. Evidence of prior HBV vaccination (positive hepatitis B surface antibody [HBsAb)) is not exclusionary.
- •Subjects unable to abstain from alcohol for 48 hours prior to admission through to completion of the Follow-up visit
研究组 & 干预措施
KSP-1007 single ascending dose
Single, ascending intravenous dose of KSP-1007
干预措施: KSP-1007 (Drug)
KSP-1007 multiple ascending dose
Multiple, ascending, intravenous doses of KSP-1007
干预措施: KSP-1007 (Drug)
KSP-1007 multiple ascending dose + Meropenem multiple dose
Multiple, ascending intravenous doses of KSP-1007 and multiple doses of meropenem (fixed dose)
干预措施: KSP-1007 (Drug)
KSP-1007 multiple ascending dose + Meropenem multiple dose
Multiple, ascending intravenous doses of KSP-1007 and multiple doses of meropenem (fixed dose)
干预措施: Meropenem (Drug)
Placebo + Meropenem multiple dose
Multiple doses of placebo (0.9% normal saline) plus multiple doses of meropenem (fixed dose)
干预措施: Meropenem (Drug)
结局指标
主要结局
Incidence of adverse events assessed by subject .
时间窗: up to Day 14
Incidence of adverse events
次要结局
- Cumulative amount of KSP-1007 excreted in urine over time(Up to 5 days after start of dosing)
- Plasma concentration versus time curve of meropenem(Up to 5 days after start of dosing)
- ECG QTcF interval(24 hours after start of dosing)
- Peak plasma concentration of KSP-1007(Up to 5 days after dosing)
- Plasma concentration of KSP-1007 versus time curve(Up to 5 days after dosing)
- Peak plasma concentration of meropenem(Up to 5 days after start of dosing)
- Renal clearance of meropenem in urine over time(Up to 5 days after start of dosing)
- Cumulative amount of meropenem excreted in urine over time(Up to 5 days after start of dosing)
- Renal clearance of KSP-1007 in urine over time(Up to 5 days after start of dosing)