AzTrials
AzTrials

Liver Transplant; ComplicationsPhase 2NCT03639623

Safety, Tolerability, and Efficacy of Saroglitazar Mg 4 mg in Liver Transplant Recipients With Nonalcoholic Fatty Liver Disease (NAFLD)

A Phase 2 study testing Saroglitazar in people with Liver Transplant; Complications and NAFLD, run by Zydus Therapeutics Inc. at 1 site in United States.

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

This is a phase 2A, single center, open-label, single-arm, 24-week study to evaluate the safety, tolerability and efficacy of Saroglitazar Magnesium 4 mg in liver transplant recipients with NAFLD. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Liver Transplant; Complications, NAFLD
What is being tested?
Saroglitazar
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
25 Feb 2019to 13 Dec 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

  • Able and willing to give written informed consent.
  • Males or females, 18 to 75 years of age.
  • Patients who are at least 6 months post-transplant for nonalcoholic steatohepatitis (NASH) or cryptogenic cirrhosis thought to be secondary to NASH are eligible for enrolment.
  • The presence of NAFLD determined by Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) prior to enrollment.
  • Patients with ≤20% variance in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin between Visit 1 and Visit 1.1.
  • History of medical compliance with immunosuppression.
  • Female subjects of non-child bearing potential or on highly effective contraception. For male subjects with female partners of childbearing potential, willing to follow highly effective contraception measures during the study, either by the male participant or his female partner or both.

Who cannot join

  • Pregnant or lactating females.
  • Patient with abnormal transaminases due to secondary intercurrent illness.
  • Patients with bile duct strictures.
  • Other causes of chronic liver disease after liver transplantation including autoimmune, viral, and alcoholic liver disease.
  • Graft cirrhosis as defined by:
  • Cirrhosis on historical liver biopsy.
Show all 24Show fewer
  • Evidence of cirrhosis on imaging including portal venous collaterals.
  • Prior history of decompensated liver disease including ascites, hepatic encephalopathy or variceal bleeding.
  • Evidence of esophageal varices on prior endoscopy.
  • Body mass index (BMI) <18 kg/m².
  • Subjects with change in body weight >5% in the 3 months prior to enrollment.
  • Subjects requiring corticosteroid or anticoagulation therapy.
  • History of myopathies or evidence of active muscle diseases.
  • Unstable cardiovascular disease.
  • History of bladder disease and/or hematuria or has current hematuria unless due to a urinary tract infection.
  • Active malignancy post-liver transplantation.
  • History of malignancy in the past 5 years and/or active neoplasm.
  • History of chronic rejection of liver transplant graft.
  • Acute cellular rejection of liver transplant graft within the past 6 months.
  • Evidence of Acute cellular rejection (ACR) or chronic rejection (CR) or alternative etiologies to NAFLD.
  • Poorly controlled diabetes as defined by an HbA1c >8.5% within the past 6 months.
  • History of excessive alcohol intake.
  • Subject tests positive for a urine drug screen.
  • Subject has a history of chronic (uncontrolled) pain.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

Other trials in United States

About this study

Official title: A Phase 2A, Single Center, Open-label, Single-arm, 24-week Study to Evaluate the Safety, Tolerability and Efficacy of Saroglitazar Magnesium 4 mg in Liver Transplant Recipients With Nonalcoholic Fatty Liver Disease (EVIDENCES VIII)

This is a phase 2A, single center, open-label, single-arm, 24-week study to evaluate the safety, tolerability and efficacy of Saroglitazar Magnesium 4 mg in liver transplant recipients with NAFLD.

Read the detailed description

This is a phase 2A, single center, open-label, single-arm, 24-week study to evaluate the safety, tolerability and efficacy of Saroglitazar Magnesium 4 mg in liver transplant recipients with NAFLD.

The study will be conducted over a period of up to 33 weeks and will include 5 weeks screening, a 24 week treatment period and 4 week follow-up period. The primary end point of the study is to assess the safety of Saroglitazar Magnesium 4 mg in liver transplant recipients with NAFLD over 24 weeks of treatment.

Being tested
Saroglitazar
Keywords
Peroxisome proliferator-activated receptors, NAFLD, NASH, Post Transplant Metabolic Syndrome
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

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

  • SaroglitazarDrug

    Also called Not any

    Saroglitazar magnesium 4 mg tablet once daily (OD) in the morning 60 minutes before breakfast without food

Study groups in NCT03639623
Study groupRoleWhat they receive
Saroglitazar Magnesium 4 mgExperimentalSaroglitazar Magnesium tablet once daily in the morning 60 minutes before breakfast
Receives: Drug: Saroglitazar

What is being measured

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

  1. Number of Participants With Adverse Events Assessed by CTCAE

    Safety measured by adverse events, vital signs, physical exams, body weight, electrocardiograms (ECGs) and lab results (including hematology, chemistry and urinalysis)

    Measured: 24 weeks

Secondary outcomes (28)

  1. Hepatic Fat

    Changes in hepatic fat as determined by MRI-PDFF from baseline to end-of-treatment (EOT)

    Measured: Baseline and week 24

  2. Liver Stiffness

    Changes in Liver stiffness as determined by MRE from baseline to end-of-treatment (EOT) Liver stiffness is a measure of a mechanical property of tissue (stiffness). This can be measured non-invasively by MR elastography, a technique that involves applying an external vibration to the abdomen and measuring the progression of shear waves through the underlying liver using MRI.

    Measured: Baseline and Week 24

  3. Frequently Sampled Intravenous Glucose Tolerance Test (Insulin Resistance Marker)

    Changes in frequently sampled intravenous glucose tolerance test (FSIVGTT) from baseline to EOT

    Measured: Baseline and Week 24

  4. Glycosylated Hemoglobin (Insulin Resistance Marker)

    Changes in glycosylated hemoglobin (HbA1c) from baseline to EOT

    Measured: Baseline and Week 24

  5. Fructosamine (Insulin Resistance Marker)

    Changes in fructosamine from baseline to EOT

    Measured: Baseline and Week 24

  6. Serum Liver Enzymes

    Changes in serum liver enzymes from baseline to EOT

    Measured: Baseline and Week 24

  7. Serum Liver Enzymes; Bilirubin

    Changes in bilirubin from baseline to EOT

    Measured: Baseline and Week 24

  8. Serum Lipids

    Changes in serum lipids from baseline to EOT

    Measured: Baseline and Week 24

  9. Small Dense Low-density Lipoprotein (Atherogenic Lipoprotein)

    Changes in small dense low-density lipoprotein (sdLDL) from baseline to EOT

    Measured: Baseline and Week 24

  10. LDL Size (Atherogenic Lipoprotein)

    Changes in LDL size from baseline to EOT

    Measured: Baseline and Week 24

  11. LDL Concentration (Atherogenic Lipoprotein)

    Changes in LDL concentration from baseline to EOT

    Measured: Baseline and Week 24

  12. Very Low-density Lipoprotein (Atherogenic Lipoprotein)

    Changes in subtypes of very low-density lipoprotein (VLDL) from baseline to EOT

    Measured: Baseline and Week 24

  13. Very Low-density Lipoprotein Chylomicron Triglyceride (Atherogenic Lipoprotein)

    Changes in VLDL chylomicron triglyceride from baseline to EOT

    Measured: Baseline and Week 24

  14. High-density Lipoprotein (Atherogenic Lipoprotein)

    Changes in high-density lipoprotein (HDL) from baseline to EOT

    Measured: Baseline and Week 24

  15. Change in Metabolic Flexibility; Time to Peak RQ

    Metabolic flexibility was measured via a whole room calorimeter (i.e. respiration chamber). The CO2 production and O2 consumption were recorded every minute for a total of 18 hours while study participants were in the respiration chamber on baseline and Week 24. Metabolic flexibility was quantified by measuring whole-body CO2 production relative to O2 consumption or respiratory quotient (RQ). The RQ oscillates between 0.7 and 1.0, which is indicative of either predominantly fatty acid or carbohydrate oxidation, respectively.

    The time to maximal carbohydrate consumption is measured by the time it takes to reach peak RQ after a standardized meal, whereas maximal carbohydrate consumption is measured at the peak of RQ vs. time curve. Next, the transition from maximal carbohydrate consumption to maximal fatty acid consumption is measured from peak RQ to lowest RQ. Finally, fasting biofuel utilization is measured in the fasting state and represents predominantly fatty acid oxidation.

    Measured: Baseline and Week 24

  16. Quality of Life (SF-36 Health Survey)

    Change in Quality of life score from baseline to EOT The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and mental composite t-score (MCS). The range for all 8 domains as well as for the composite t-scores is from 0 to 100 with 100 as best possible health status and 0 as the worst health status

    Measured: Baseline and Week 24

  17. Peak Plasma Concentration [Cmax]

    Pharmacokinetics of Saroglitazar following first and last dose.

    Measured: PK Sampling time points: Day 1 and Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  18. Time to Reach Peak Plasma Concentration [Tmax]

    Pharmacokinetics of Saroglitazar following first and last dose

    Measured: PK Sampling time points: Day 1 and Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  19. Area Under Plasma Concentration vs. Time Curve Till the Last Time Point [AUC0-t]

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Day 1 visit at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  20. Area Under Plasma Concentration vs. Time Curve Extrapolated to the Infinity [AUC0-∞]

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Day 1 visit at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  21. Area Under Plasma Concentration vs. Time Curve in a 24 h Dosing Interval [AUCtau]

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Day 1 and Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  22. Elimination Rate Constant [λz]

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Day 1 and Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  23. Elimination Half-life [t1/2]

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Day 1 and Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  24. Apparent Volume of Distribution [Vd/F]

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Day 1 (Baseline) and Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  25. Apparent Clearance [CL/F]

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Day 1 and Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  26. Minimal or Trough Plasma Concentration [Cmin]

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Week 24 visit at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  27. Accumulation Index Calculated as a Ratio of AUCtau (Last Dose)/AUCtau (First Dose)

    Pharmacokinetics of Saroglitazar

    Measured: PK Sampling time points: Day 1 and Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

  28. Fluctuation Index

    Fluctuation index is the peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100

    Measured: PK Sampling time points: Week 24 visits at pre-dose (0), 0.5, 1.0, 2, 3, 4, 6, 8, 10 and 24-hour post-dose

Timeline

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

  1. First posted21 Aug 2018
  2. Study start25 Feb 2019
  3. Primary completion13 Dec 2021
  4. Study completion13 Dec 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03639623
Sponsor's protocol ID
SARO.17.010
Status last verified
Oct 2024
First submitted
15 Aug 2018
Last updated
24 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bhati C, Idowu MO, Sanyal AJ, Rivera M, Driscoll C, Stravitz RT, Kohli DR, Matherly S, Puri P, Gilles H, Cotterell A, Levy M, Sterling RK, Luketic VA, Lee H, Sharma A, Siddiqui MS. Long-term Outcomes in Patients Undergoing Liver Transplantation for Nonalcoholic Steatohepatitis-Related Cirrhosis. Transplantation. 2017 Aug;101(8):1867-1874. doi: 10.1097/TP.0000000000001709.

    PubMed 28296807

  • Siddiqui MS, Parmar D, Shaikh F, Forsgren M, Patel S, Bui AT, Boyett S, Patel V, Sanyal AJ. Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients. Liver Transpl. 2023 Sep 1;29(9):979-986. doi: 10.1097/LVT.0000000000000110. Epub 2023 Feb 28.

    PubMed 36847136

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Saroglitazar in people with Liver Transplant; Complications and NAFLD, run by Zydus Therapeutics Inc. at 1 site in United States.

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 7 inclusion and 24 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 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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. 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 24 Oct 2024). 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?

Number of Participants With Adverse Events Assessed by CTCAE (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03639623, which also lists 2 linked publications.

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 24 Oct 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in