Phase 2
N=83
Safety, Tolerability and Efficacy of Nidufexor in Patients With Diabetic Nephropathy
Diabetic Nephropathy
Bottom Line
View on ClinicalTrials.gov: NCT03804879 ↗Enrolled (actual)
83
Serious AEs
4.8%
Results posted
Jun 2022
Primary outcome: Primary: Ratio to Baseline in Urinary Albumin to Creatinine Ratio (UACR) — 0.90; 1.06; 0.83; 1.00 Ratio to baseline
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Nidufexor (Drug); Placebo (Other); Standard of Care (SoC) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- May 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Ratio to Baseline in Urinary Albumin to Creatinine Ratio (UACR) |
0.90; 1.06; 0.83; 1.00; 0.85; 1.05 | — |
| PRIMARY Ratio to Baseline in 24 Hour Urinary Albumin at Week 24 (Day 169) |
0.58; 0.91 | — |
| PRIMARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
29; 25; 2; 2 | — |
| SECONDARY Ratio to Baseline in Estimated Glomerular Filtration Rate (eGFR) |
0.95; 0.96; 0.94; 0.94; 0.98; 0.96 | — |
| SECONDARY Maximum Peak Observed Concentration (Cmax) of LMB763 |
1090; 1300 | — |
| SECONDARY Time to Reach Maximum Blood Concentrations (Tmax) of LMB763 |
3.25; 2 | — |
| SECONDARY Area Under the Blood Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of LMB763 |
3710; 4850 | — |
| SECONDARY Ratio to Baseline in Free Water Clearance |
0.97; 0.97 | — |
| SECONDARY Ratio to Baseline in Lipoprotein A at Day 85 |
0.72; 0.95 | — |
| SECONDARY Ratio to Baseline in Lipoprotein A at Day 169 |
0.75; 0.89 | — |
| SECONDARY Percent Change From Baseline in Weight |
-0.08; -0.13; -0.57; -0.03; -0.69; -0.24 | — |
| SECONDARY Percent Change From Baseline in Body Mass Index (BMI) |
-0.01; -0.05; -0.19; -0.02; -0.23; -0.07 | — |
| SECONDARY Change From Baseline in Waist-to-hip Ratio |
-0.00; -0.00; -0.00; 0.00; -0.00; 0.00 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT03804879). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.