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Safety, Tolerability and Efficacy of Saroglitazar Magnesium 4 mg in Liver Transplant Recipients With Nonalcoholic Fatty Liver Disease (EVIDENCES VIII)

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ClinicalTrials.gov Identifier: NCT03639623
Recruitment Status : Recruiting
First Posted : August 21, 2018
Last Update Posted : January 7, 2019
Sponsor:
Information provided by (Responsible Party):
Zydus Discovery DMCC

Tracking Information
First Submitted Date  ICMJE August 15, 2018
First Posted Date  ICMJE August 21, 2018
Last Update Posted Date January 7, 2019
Estimated Study Start Date  ICMJE February 4, 2019
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2018)
Number of participants with adverse events assessed by CTCAE [ Time Frame: 24 weeks ]
Safety measured by adverse events, vital signs, physical exams, body weight, electrocardiograms (ECGs) and lab results (including hematology, chemistry and urinalysis)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03639623 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2018)
  • Hepatic fat [ Time Frame: 24 weeks ]
    Changes in hepatic fat as determined by MRI-PDFF and MRE from baseline to end-of-treatment (EOT)
  • Metabolic flexibility [ Time Frame: 24 weeks ]
    Changes in metabolic flexibility from baseline to EOT
  • Frequently sampled intravenous glucose tolerance test (Insulin resistance marker) [ Time Frame: 24 weeks ]
    Changes in frequently sampled intravenous glucose tolerance test (FSIVGTT) from baseline to EOT
  • Glycosylated hemoglobin (Insulin resistance marker) [ Time Frame: 24 weeks ]
    Changes in glycosylated hemoglobin (HbA1c) from baseline to EOT
  • Fructosamine (Insulin resistance marker) [ Time Frame: 24 weeks ]
    Changes in fructosamine from baseline to EOT
  • Serum liver enzymes [ Time Frame: 24 weeks ]
    Changes in serum liver enzymes from baseline to EOT
  • Serum lipids [ Time Frame: 24 weeks ]
    Changes in serum lipids from baseline to EOT
  • Small dense low-density lipoprotein (Atherogenic lipoprotein) [ Time Frame: 24 weeks ]
    Changes in small dense low-density lipoprotein (sdLDL) from baseline to EOT
  • LDL size and concentration (Atherogenic lipoprotein) [ Time Frame: 24 weeks ]
    Changes in LDL size and concentration from baseline to EOT
  • Very low-density lipoprotein (Atherogenic lipoprotein) [ Time Frame: 24 weeks ]
    Changes in subtypes of very low-density lipoprotein (VLDL) from baseline to EOT
  • High-density lipoprotein (Atherogenic lipoprotein) [ Time Frame: 24 weeks ]
    Changes in high-density lipoprotein (HDL) from baseline to EOT
  • Quality of life (SF-36 Health Survey) [ Time Frame: 24 weeks ]
    Change in Quality of life score from baseline to EOT
  • Peak plasma concentration [Cmax] [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Time to reach peak plasma concentration [Tmax] [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Area under plasma concentration vs. time curve till the last time point [AUC0-t] [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Area under plasma concentration vs. time curve extrapolated to the infinity [AUC0-∞] after first dose [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first dose
  • Area under plasma concentration vs. time curve in a 24 h dosing interval [AUCtau] [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Elimination rate constant [λz] [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Elimination half-life [t1/2] [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Apparent volume of distribution [Vd/F] [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Apparent clearance [CL/F] [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Minimal or trough plasma concentration [Cmin] -for last dose only [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following last dose
  • Accumulation index calculated as a ratio of AUCtau (last dose)/AUCtau (first dose) [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
  • Fluctuation index [ Time Frame: 24 weeks ]
    Pharmacokinetics of Saroglitazar following first and last dose
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability and Efficacy of Saroglitazar Magnesium 4 mg in Liver Transplant Recipients With Nonalcoholic Fatty Liver Disease (EVIDENCES VIII)
Official Title  ICMJE 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
Brief 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 as assessed by MRI-PDFF and MRE. 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-alcoholic Fatty Liver Disease in Liver Transplant Recipients
Intervention  ICMJE Drug: Saroglitazar Magnesium 4 mg
All subjects will receive Saroglitazar Magnesium tablet once daily in the morning 60 minutes before breakfast
Study Arms  ICMJE Experimental: Saroglitazar Magnesium 4 mg
Saroglitazar Magnesium tablet once daily in the morning 60 minutes before breakfast
Intervention: Drug: Saroglitazar Magnesium 4 mg
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2018)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Deven Parmar, MD FCP +1-609-730-1900 ext 407 deven.parmar@zydusdiscovery.ae
Contact: Neelakant Krishnan, BDS PGDCR +1-609-730-1900 ext 222 Neelakant.Krishnan@zyduscadila.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03639623
Other Study ID Numbers  ICMJE SARO.17.010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Zydus Discovery DMCC
Study Sponsor  ICMJE Zydus Discovery DMCC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Deven Parmar, MD FCP Zydus Discovery DMCC
PRS Account Zydus Discovery DMCC
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP