Safety, Tolerability and Efficacy of Saroglitazar Mg 4 mg in Liver Transplant Recipients With NAFLD

NAFLD Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03639623
• Other study ID #: SARO.17.010
• Status: Completed
• Phase: Phase 2
• Start date: February 25, 2019
• Est. completion date: December 13, 2021

Study information

• Verified date: October 2023
• Source: Zydus Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 13, 2021
• Est. primary completion date: December 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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 MRI-PDFF prior to enrollment.
• Patients with =20% variance in the levels of ALT, AST, 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.

Exclusion Criteria:

• 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:

1. Cirrhosis on historical liver biopsy.

2. Evidence of cirrhosis on imaging including portal venous collaterals.

3. Prior history of decompensated liver disease including ascites, hepatic encephalopathy or variceal bleeding.

4. 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.

Related Conditions & MeSH terms

• Liver Transplant; Complications
• NAFLD
• Non-alcoholic Fatty Liver Disease

Intervention

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

Locations

Country	Name	City	State
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Zydus Therapeutics Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	24 weeks
Secondary	Hepatic fat	Changes in hepatic fat as determined by MRI-PDFF and MRE from baseline to end-of-treatment (EOT)	24 weeks
Secondary	Metabolic flexibility	Changes in metabolic flexibility from baseline to EOT	24 weeks
Secondary	Frequently sampled intravenous glucose tolerance test (Insulin resistance marker)	Changes in frequently sampled intravenous glucose tolerance test (FSIVGTT) from baseline to EOT	24 weeks
Secondary	Glycosylated hemoglobin (Insulin resistance marker)	Changes in glycosylated hemoglobin (HbA1c) from baseline to EOT	24 weeks
Secondary	Fructosamine (Insulin resistance marker)	Changes in fructosamine from baseline to EOT	24 weeks
Secondary	Serum liver enzymes	Changes in serum liver enzymes from baseline to EOT	24 weeks
Secondary	Serum lipids	Changes in serum lipids from baseline to EOT	24 weeks
Secondary	Small dense low-density lipoprotein (Atherogenic lipoprotein)	Changes in small dense low-density lipoprotein (sdLDL) from baseline to EOT	24 weeks
Secondary	LDL size and concentration (Atherogenic lipoprotein)	Changes in LDL size and concentration from baseline to EOT	24 weeks
Secondary	Very low-density lipoprotein (Atherogenic lipoprotein)	Changes in subtypes of very low-density lipoprotein (VLDL) from baseline to EOT	24 weeks
Secondary	High-density lipoprotein (Atherogenic lipoprotein)	Changes in high-density lipoprotein (HDL) from baseline to EOT	24 weeks
Secondary	Quality of life (SF-36 Health Survey)	Change in Quality of life score from baseline to EOT	24 weeks
Secondary	Peak plasma concentration [Cmax]	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Time to reach peak plasma concentration [Tmax]	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Area under plasma concentration vs. time curve till the last time point [AUC0-t]	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Area under plasma concentration vs. time curve extrapolated to the infinity [AUC0-8] after first dose	Pharmacokinetics of Saroglitazar following first dose	24 weeks
Secondary	Area under plasma concentration vs. time curve in a 24 h dosing interval [AUCtau]	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Elimination rate constant [?z]	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Elimination half-life [t1/2]	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Apparent volume of distribution [Vd/F]	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Apparent clearance [CL/F]	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Minimal or trough plasma concentration [Cmin] -for last dose only	Pharmacokinetics of Saroglitazar following last dose	24 weeks
Secondary	Accumulation index calculated as a ratio of AUCtau (last dose)/AUCtau (first dose)	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks
Secondary	Fluctuation index	Pharmacokinetics of Saroglitazar following first and last dose	24 weeks