Clinical trial NCT03804879: Safety, Tolerability and Efficacy of Nidufexor in Patients With Diabetic Nephropathy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathy
Keywords: diabetes
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-01-15
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

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.

Primary outcomes:
measure: Ratio to Baseline in Urinary Albumin to Creatinine Ratio (UACR)
timeFrame: Baseline and days 14, 29, 57, 85, 113, 141 and 169
measure: Ratio to Baseline in 24 Hour Urinary Albumin at Week 24 (Day 169)
timeFrame: Baseline and day 169
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From the start of treatment to 28 days after end of treatment, assessed up to maximum duration of 197 days
Secondary outcomes:
measure: Ratio to Baseline in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline and days 14, 29, 57, 85, 113, 141 and 169
measure: Maximum Peak Observed Concentration (Cmax) of LMB763
timeFrame: pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14
measure: Time to Reach Maximum Blood Concentrations (Tmax) of LMB763
timeFrame: pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14
measure: Area Under the Blood Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of LMB763
timeFrame: pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14
measure: Ratio to Baseline in Free Water Clearance
timeFrame: Baseline and day 169
measure: Ratio to Baseline in Lipoprotein A at Day 85
timeFrame: Baseline and day 85
measure: Ratio to Baseline in Lipoprotein A at Day 169
timeFrame: Baseline and day 169
measure: Percent Change From Baseline in Weight
timeFrame: Baseline and days 14, 29, 57, 85, 113, 141 and 169
measure: Percent Change From Baseline in Body Mass Index (BMI)
timeFrame: Baseline and days 14, 29, 57, 85, 113, 141 and 169
measure: Change From Baseline in Waist-to-hip Ratio
timeFrame: Baseline and days 14, 29, 57, 85, 113, 141 and 169
Other outcomes:
Locations:
city: Miami Lakes
country: United States
facility: Novartis Investigative Site
state: Florida
city: Albany
country: United States
facility: Novartis Investigative Site
state: New York
city: Norman
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: El Paso
country: United States
facility: Novartis Investigative Site
state: Texas
city: Sugar Land
country: United States
facility: Novartis Investigative Site
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
state: Nordrhine Westphalia
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Elsterwerda
country: Germany
facility: Novartis Investigative Site
city: Amman
country: Jordan
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Saida
country: Lebanon
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Talas / Kayseri
country: Turkey
facility: Novartis Investigative Site
Study officials:
References: