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Diabetic NephropathyPhase 2NCT03804879

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

A Phase 2 study testing Nidufexor in people with Diabetic Nephropathy, run by Novartis Pharmaceuticals at 18 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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)). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Diabetic Nephropathy
What is being tested?
Nidufexor
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
83 participants
Where
18 sitesin 7 countries
Study dates
17 Dec 2018to 3 May 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 9Show fewer
  • 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.

Trial locations and contacts

18 sites in 7 countries.

18 sites in 7 countries

United States5 sites
  • Novartis Investigative Site

    Albany, New York, 12206

  • Novartis Investigative Site

    El Paso, Texas, 79935

  • Novartis Investigative Site

    Miami Lakes, Florida, 33014

  • Novartis Investigative Site

    Norman, Oklahoma, 73069

  • Novartis Investigative Site

    Sugar Land, Texas, 77479

Other trials in United States

Argentina3 sites
  • Novartis Investigative Site

    Buenos Aires, C1120AAC

  • Novartis Investigative Site

    CABA, Buenos Aires, 1407

  • Novartis Investigative Site

    CABA, Buenos Aires, C1056ABJ

Other trials in Argentina

Germany3 sites
  • Novartis Investigative Site

    Berlin, 10787

  • Novartis Investigative Site

    Elsterwerda, 04910

  • Novartis Investigative Site

    Essen, Nordrhine Westphalia, 45136

Other trials in Germany

Turkey (Türkiye)3 sites
  • Novartis Investigative Site

    Istanbul, TUR, 34098

  • Novartis Investigative Site

    Kocaeli, 41380

  • Novartis Investigative Site

    Talas / Kayseri, 38039

Other trials in Turkey (Türkiye)

Lebanon2 sites
  • Novartis Investigative Site

    El Achrafiyé

  • Novartis Investigative Site

    Saida, 652

Other trials in Lebanon

Czechia1 site
  • Novartis Investigative Site

    Prague, 12808

Other trials in Czechia

Jordan1 site
  • Novartis Investigative Site

    Amman, 11941

Other trials in Jordan

About this study

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

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.

Read the 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.

Being tested
Nidufexor, Placebo, Standard of Care (SoC)
Keywords
diabetes
Medical subject headings
Diabetic Nephropathies, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NidufexorDrug

    Also called LMB763

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

  • PlaceboOther

    Placebo capsules for oral administration

  • Standard of Care (SoC)Drug

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

Study groups in NCT03804879
Study groupRoleWhat they receive
LMB763Experimental50 mg LMB763 (two LMB763 25 mg capsules) were orally administered once daily for 24 weeks in addition to SoC.
Receives: Drug: Nidufexor; Drug: Standard of Care (SoC)
PlaceboPlacebo comparatorPlacebo was orally administered once daily for 24 weeks in addition to SoC.
Receives: Other: Placebo; Drug: Standard of Care (SoC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: Baseline and day 169

  3. 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.

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

Secondary outcomes (10)
  1. Ratio to Baseline in Estimated Glomerular Filtration Rate (eGFR)

    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.

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

  2. Maximum Peak Observed Concentration (Cmax) of LMB763

    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.

    Measured: pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14

  3. Time to Reach Maximum Blood Concentrations (Tmax) of LMB763

    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.

    Measured: pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14

  4. Area Under the Blood Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of LMB763

    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.

    Measured: pre-dose and 1, 2, 4 and 6 hours after LMB763 administration on Day 1 and Day 14

  5. Ratio to Baseline in Free Water Clearance

    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.

    Measured: Baseline and day 169

  6. Ratio to Baseline in Lipoprotein A at Day 85

    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.

    Measured: Baseline and day 85

  7. Ratio to Baseline in Lipoprotein A at Day 169

    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.

    Measured: Baseline and day 169

  8. Percent Change From Baseline in Weight

    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.

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

  9. Percent Change From Baseline in Body Mass Index (BMI)

    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.

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

  10. Change From Baseline in Waist-to-hip Ratio

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jan 2019
  2. Study start17 Dec 2018
  3. Primary completion3 May 2021
  4. Study completion3 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03804879
Sponsor's protocol ID
CLMB763X2202
Other IDs
2018-002491-40, 2018
Status last verified
Aug 2022
First submitted
26 Nov 2018
Last updated
10 Aug 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nidufexor in people with Diabetic Nephropathy, run by Novartis Pharmaceuticals at 18 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, Argentina, Germany, Turkey (Türkiye), Lebanon and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ratio to Baseline in Urinary Albumin to Creatinine Ratio (UACR) (time frame: Baseline and days 14, 29, 57, 85, 113, 141 and 169). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2022.

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