A Phase 1, Open-label, Single-dose, Multi-center, Parallel Group Study to Evaluate the Pharmacokinetics of TNO155 in Participants With Mild, Moderate, or Severe Renal Impairment Compared to Matched Healthy Control Participants
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155
研究概览
简要总结
The purpose of this Phase 1 study is to evaluate the effect of various degrees of renal impairment on plasma pharmacokinetics (PK), safety and tolerability of TNO155. The results of this study will guide the Novartis recommendation regarding whether or not a dose adjustment may be needed when treating patients with renal impairment
详细描述
This is a study to evaluate the PK of TNO155 in participants with mild, moderate or severe renal impairment compared to matched healthy control participants with normal renal function. The study will be divided into 2 parts. Participants in the renal impairment groups will be staged by their respective degree of renal function (mild, moderate, or severe) according to the estimated glomerular filtration rate (eGFR) determined at the screening visit. Each renal impairment participant must be matched to a healthy control participant with respect to age (±10 years), body weight (±20%) and sex. Each participant in the healthy control group (Group 1) can be matched to one or more participants from any renal impairment group (Groups 2, 3, and 4).
On Day 1 morning, participants will receive a single oral dose of TNO155 .All participants will be domiciled from Day -1 until Day 11. All participants should have a poststudy safety follow-up contact conducted approximately 30 days after administration of study treatment. The study will be considered complete once all the participants have finished the required assessments, dropped out, or been lost to follow-up before completing the required assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All participants Participants must weigh at least 50 kg and no more than 120 kg and must have a body mass index (BMI) within the range of 18.0 to 38.0 kg/m2, inclusive, for healthy participants. Must be a non-smoker or and agree to remain a non-smoker from screening until the End of Study.
- •eGFR as determined by Chronic Kidney Disease Epidemiology Collaboration [CKD EPI] equation and conversion within normal range as determined by GFR 90 mL/min at screening and baseline.
- •Groups 2 to 4
- •Participants with different levels of impaired renal function satisfying criteria for renal impairment as determined at screening by the eGFR at screening
- •Participants must have documented stable renal disease without evidence of renal progressive disease
排除标准
- •All Participants
- •Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort), within 4 weeks prior to dosing until completion of the End of Study Visit.
- •Participant has received a renal transplant at any time in the past and is on immunosuppressant therapy Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard lower limit, at screening or baseline.
- •Uncontrolled hypertension despite medical treatment at screening or baseline. Group 1
- •Significant illness, which has not been resolved within 2 weeks prior to dosing of study treatment.
- •History or presence of renal disease or kidney injury Groups 2, 3 and 4
- •Severe albuminuria
- •Other laboratory values grade 2 severity according to NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE)
- •Participants undergoing any method of dialysis.
- •Participants with renal impairment due to hepatic disease (hepatorenal syndrome).
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Group 1
Healthy control participants with normal renal function
干预措施: TNO155 (Drug)
Group 2
Mild renal impairment
干预措施: TNO155 (Drug)
Group 3
Moderate renal impairment
干预措施: TNO155 (Drug)
Group 4
Severe renal impairment
干预措施: TNO155 (Drug)
结局指标
主要结局
Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155
时间窗: Up to 240 hours post single dose
AUClast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Maximum (peak) observed plasma concentration (Cmax) of TNO155
时间窗: Up to 240 hours post single dose
Cmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time to reach maximum observed plasma concentration (Tmax) of TNO155
时间窗: Up to 240 hours post single dose
Tmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods
Elimination half-life (T1/2) of TNO155
时间窗: Up to 240 hours post single dose
T1/2 will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Sampling time of the last measurable plasma concentration (Tlast) of TNO155
时间窗: Up to 240 hours post single dose
Tlast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Apparent plasma clearance (CL/F) of TNO155
时间窗: Up to 240 hours post single dose
CL/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Apparent volume of distribution during terminal phase (Vz/F) of TNO155
时间窗: Up to 240 hours post single dose
Vz/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
AUC from time zero to time "t" (AUC0-t) of TNO155
时间窗: AUC from time zero to time "t" (AUC0-t) of TNO155
AUC0-t will be calculated as needed based on TNO155 plasma concentrations and non-compartmental methods. The definition of time "t" may be data-driven post-hoc to mitigate treatment bias due to within participant differences in Tlast between the treatments, or may be selected to allow between-study exposure comparisons that use a common time window.
AUC from time zero to infinity (AUCinf) of TNO155
时间窗: Up to 240 hours post single dose
AUCinf will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
次要结局
- Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 30 days post single dose)
- Unbound Cmax (Cmax,u) of TNO155(Up to 240 hours post single dose)
- Unbound AUClast (AUClast,u) of TNO155(Up to 240 hours post single dose)
- Unbound AUCinf (AUCinf,u) of TNO155(Up to 240 hours post single dose)
- Unbound CL/F (CL/F,u) of TNO155(Up to 240 hours post single dose)
- Renal clearance (CLr) of TNO155(Up to 240 hours post single dose)
- Apparent non-renal clearance (CLNR/F) of TNO155(Up to 240 hours post single dose)
- Fraction of dose excreted in urine (fe) of TNO155(Up to 240 hours post single dose)