Safety, Tolerability and Efficacy of Nidufexor in Patients With Diabetic Nephropathy

NCT03804879 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CLMB763X22022018-002491-40
• Study Type: interventional
• Target: 83
• Locations: 7 countries
• Sites: 18

Brief Summary

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.

Conditions

Diabetic Nephropathy

Keywords

diabetes

Outcome Measures

Primary Outcomes (3)

• Ratio to Baseline in Urinary Albumin to Creatinine Ratio (UACR)

  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.

  Baseline and days 14, 29, 57, 85, 113, 141 and 169

• Ratio to Baseline in 24 Hour Urinary Albumin at Week 24 (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.

  Baseline and day 169

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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.

  From the start of treatment to 28 days after end of treatment, assessed up to maximum duration of 197 days

Secondary Outcomes (10)

• 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

• 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

• 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 Free Water Clearance

  Baseline and day 169

Study Arms (2)

LMB763

EXPERIMENTAL

50 mg LMB763 (two LMB763 25 mg capsules) were orally administered once daily for 24 weeks in addition to SoC.

Drug: Nidufexor; Drug: Standard of Care (SoC)

Placebo

PLACEBO COMPARATOR

Placebo was orally administered once daily for 24 weeks in addition to SoC.

Other: Placebo; Drug: Standard of Care (SoC)

Interventions

Nidufexor DRUG

50 mg (two 25 mg) LMB763 capsules for oral administration

Also known as: LMB763

LMB763

Placebo OTHER

Placebo capsules for oral administration

Placebo

Standard of Care (SoC) DRUG

Optimal tolerated doses of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)

LMB763; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Novartis Investigative Site

Miami Lakes, Florida, 33014, United States

Location

Novartis Investigative Site

Albany, New York, 12206, United States

Location

Novartis Investigative Site

Norman, Oklahoma, 73069, United States

Location

Novartis Investigative Site

El Paso, Texas, 79935, United States

Location

Novartis Investigative Site

Sugar Land, Texas, 77479, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, 1407, Argentina

Location

Novartis Investigative Site

CABA, Buenos Aires, C1056ABJ, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1120AAC, Argentina

Location

Novartis Investigative Site

Prague, 12808, Czechia

Location

Novartis Investigative Site

Essen, Nordrhine Westphalia, 45136, Germany

Location

Novartis Investigative Site

Berlin, 10787, Germany

Location

Novartis Investigative Site

Elsterwerda, 04910, Germany

Location

Novartis Investigative Site

Amman, 11941, Jordan

Location

Novartis Investigative Site

El Achrafiyé, Lebanon

Location

Novartis Investigative Site

Saida, 652, Lebanon

Location

Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

Location

Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

Location

Novartis Investigative Site

Talas / Kayseri, 38039, Turkey (Türkiye)

Location

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Diabetic Nephropathies; Diabetes Mellitus

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2018
• First Posted: January 15, 2019
• Study Start: December 17, 2018
• Primary Completion: May 3, 2021
• Study Completion: May 3, 2021
• Last Updated: August 10, 2022
• Results First Posted: June 29, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

US (5); JO (1); TU (3); AR (3); CZ (1); DE (3); LE (2)