A Randomized Patient-and-physician Blinded, Placebo-controlled, 24-week Study to Assess the Safety, Tolerability and Efficacy of LMB763 in Patients With Diabetic Nephropathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Ratio to Baseline in 24 Hour Urinary Albumin at Week 24 (Day 169)
研究概览
简要总结
Nidufexor addresses fibrosis, oxidative stress, inflammation and cell death, and therefore has the potential to improve the management of diabetic kidney disease when added to the standard of care (SoC) (angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)).
This non-confirmatory Phase 2 study was designed to determine the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of nidufexor in combination with ACEI or ARB at a dose level that is SoC as judged by the study doctor in patients with type 2 diabetes and nephropathy.
详细描述
This was a non-confirmatory, multicenter, patient- and investigator-blinded, randomized, and placebo-controlled, proof-of concept trial assessing nidufexor vs. placebo in patients receiving standard of care (optimal tolerated doses of ARB or ACEI) for diabetic nephropathy due to type 2 diabetes.
The study consisted of three distinct study periods:
Screening (Day -30 to Day-1): lasted up to a maximum of 30 days and comprised a screening / baseline assessment. This visit was used to confirm that the study inclusion and exclusion criteria were met and served as baseline assessment prior to randomization. Participant randomization occurred prior to day 1 as soon as participant eligibility was confirmed.
Treatment period (Day 1-168): Participants were randomized in a 1:1 ratio to receive nidufexor 50 mg or placebo once daily for 24 weeks. Nidufexor and placebo were given in addition to SoC (optimal tolerated doses of ARB or ACEI).
End of Study (EOS) and Safety follow-up (Day 169 to Day 197): Study assessments were performed until the EOS visit (Day 169). Post Study Safety Contact occurred approximately 28 days after discontinuing study treatment until day 197.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- 否
入选标准
- •Male/female patients, 18-75 years
- •Written informed consent
- •Diagnosis of Type 2 diabetes mellitus, with diagnosis made at least 6 months prior to screening
- •Diabetic nephropathy as evidenced by Urine albumin-Cr ratio (UACR) ≥300 mg/g Cr at screening while receiving a dose of angiotensin converting enzyme inhibitor or angiotensin receptor blocker that is the standard of care as judged by the study doctor.
排除标准
- •History of type 1 diabetes mellitus
- •Severe renal impairment manifesting as serum creatinine eGFR < 30 mL/min/1.73 m^2 at screening
- •Pregnant or nursing (lactating) women
- •Women of child-bearing potential, unless they are using basic methods of contraception during dosing of study treatment
- •Uncontrolled diabetes mellitus at screening
- •History or current diagnosis of ECG abnormalities prior to first study dose
- •History of kidney disease other than diabetic nephropathy at screening
- •Uncontrolled hypertension at screening
- •Use of prohibited medications, including but not limited to GLP-1 agonists and SGLT2 inhibitors.
研究组 & 干预措施
LMB763
50 mg LMB763 (two LMB763 25 mg capsules) were orally administered once daily for 24 weeks in addition to SoC.
干预措施: Nidufexor (Drug)
LMB763
50 mg LMB763 (two LMB763 25 mg capsules) were orally administered once daily for 24 weeks in addition to SoC.
干预措施: Standard of Care (SoC) (Drug)
Placebo
Placebo was orally administered once daily for 24 weeks in addition to SoC.
干预措施: Placebo (Other)
Placebo
Placebo was orally administered once daily for 24 weeks in addition to SoC.
干预措施: Standard of Care (SoC) (Drug)
结局指标
主要结局
Ratio to Baseline in 24 Hour Urinary Albumin at Week 24 (Day 169)
时间窗: Baseline and day 169
Albuminuria describes the existence of albumin in the urine and the gold-standard to assess albuminuria is 24-hour urinary albumin excretion (milligram/24 hours). An analysis of covariance (ANCOVA) with treatment as the classification factor and log-transformed baseline as the covariate was conducted for log-transformed ratio to baseline 24-hour urinary albumin excretion. Baseline is the last measurement prior to treatment administration. No methods for imputation of missing data were used. Values reported were back-transformed to original scale. A lower score in the ratio to baseline indicates improvement.
Ratio to Baseline in Urinary Albumin to Creatinine Ratio (UACR)
时间窗: Baseline and days 14, 29, 57, 85, 113, 141 and 169
UACR is a ratio between albumin and creatinine, and it estimates 24-hour urine albumin excretion. UACR (mg/mmol) = urine albumin \[mg/L\] / urine creatinine \[mmol/L\]. UACR was analyzed on a log-scale fitting a repeated measures mixed model including treatment and visit as fixed effects and log of baseline as continuous covariate. Baseline is the last measurement prior to treatment administration. No methods for imputation of missing data were used. Values reported were back-transformed to original scale. A lower score in the ratio to baseline indicates improvement.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the start of treatment to 28 days after end of treatment, assessed up to maximum duration of 197 days
Number of participants with AEs and SAEs including significant changes from baseline in vital signs, electrocardiograms and laboratory values qualifying and reported as AEs. The category Number of participants with AEs includes also the number of participants with SAEs. The number of participants in each category is reported in the table.
次要结局
- Ratio to Baseline in Lipoprotein A at Day 169(Baseline and day 169)
- Change From Baseline in Waist-to-hip Ratio(Baseline and days 14, 29, 57, 85, 113, 141 and 169)
- Percent Change From Baseline in Body Mass Index (BMI)(Baseline and days 14, 29, 57, 85, 113, 141 and 169)
- Ratio to Baseline in Free Water Clearance(Baseline and day 169)
- Percent Change From Baseline in Weight(Baseline and days 14, 29, 57, 85, 113, 141 and 169)
- Time to Reach Maximum Blood Concentrations (Tmax) of LMB763(pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14)
- Ratio to Baseline in Estimated Glomerular Filtration Rate (eGFR)(Baseline and days 14, 29, 57, 85, 113, 141 and 169)
- Maximum Peak Observed Concentration (Cmax) of LMB763(pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14)
- Area Under the Blood Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of LMB763(pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14)
- Ratio to Baseline in Lipoprotein A at Day 85(Baseline and day 85)