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.

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

Diabetic Nephropathy

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.

Nidufexor

Placebo

Standard of Care (SoC)

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

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.

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.

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.

Estimate Glomerular Filtration Rate (GFR) calculates estimated GFR (eGFR) from serum
creatinine levels to assess kidney function. eGFR (milliliter/minute) 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 higher score in the ratio to
baseline indicates improvement.

Pharmacokinetic (PK) parameters were calculated based on LMB763 blood concentrations
determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS)
method. Cmax was determined using non-compartmental methods. No methods for imputation of
missing data were used.

Pharmacokinetic (PK) parameters were calculated based on LMB763 blood concentrations
determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS)
method. Tmax was determined using non-compartmental methods. Actual time of sample
collection was used (not the nominal time point as per scheduled assessment). No methods
for imputation of missing data were used.

Pharmacokinetic (PK) parameters were calculated based on LMB763 blood concentrations
determined by a validated liquid chromatography and tandem mass spectrometry (LC-MS/MS)
method. AUClast was determined using non-compartmental methods. No methods for imputation
of missing data were used.

The free water clearance (mL/min) was calculated using the following formula: (Total
Volume (mL) / Elapsed Date & Time (min)) * (1-24 hr Urine Osmolality (mOsmol/kg)/ Serum
Osmolality (mOsmol/kg))

The result of free water clearance was rounded to one decimal place prior to statistical
analysis. 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 free water clearance. 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 higher score in the ratio to baseline indicates
improvement.

Lipoprotein A (gram/liter) is a component of the lipid profile which is a panel of blood
tests used to find abnormalities in lipids. Ratio to baseline in Lipoprotein A 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.

Change from baseline in weight 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 negative score in the percent change from baseline
indicates improvement.

BMI was determined by height and weight measurements: Body weight (kg)/ [Height (m)]^2.
Change from baseline in BMI 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 negative score in the percent change from baseline indicates
improvement.

Waist-to-hip ratio was derived using waist circumference and hip circumference, which was
measured at the greatest protrusion of the buttocks. Change from baseline in waist-to-hip
ratio 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 negative score in the change from baseline indicates improvement.

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

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

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

About this trial

Study ID

Status

Type

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Placebo

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Trial Timing

What is this trial about?

What are the participation requirements?

Locations

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