Saroglitazar for Liver Cirrhosis
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Zydus Therapeutics Inc.
Must not be taking: Antibiotics, Antifungals, Antivirals, others
Disqualifiers: Malignancy, Surgery, Infection, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?A Phase 1, Open-label Extension Groups Study in Subjects having Hepatic Impairment with Cirrhosis due to Cholestatic Liver Disease
Will I have to stop taking my current medications?
The trial protocol suggests that participants may need to stop taking certain medications, especially those that could affect drug absorption, metabolism, or elimination. However, therapies for hepatic disease and associated disorders that have been stable for at least 30 days may be allowed, as well as some over-the-counter products approved by the Investigator.
What data supports the effectiveness of the drug Saroglitazar for liver cirrhosis?
Research shows that Saroglitazar, a drug that activates certain proteins in the body, has been effective in treating liver conditions like non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which can lead to liver cirrhosis. It has been shown to improve liver health in these conditions, suggesting potential benefits for liver cirrhosis as well.
12345Is Saroglitazar safe for humans?
Saroglitazar has been found to be safe and well-tolerated in humans, including those with varying degrees of liver function, based on studies involving single doses and longer-term use for conditions like non-alcoholic fatty liver disease.
12467What makes the drug Saroglitazar unique for treating liver cirrhosis?
Saroglitazar is unique because it is a dual PPAR-α/γ agonist, which means it activates specific proteins that help regulate fat metabolism and inflammation, potentially benefiting liver conditions like cirrhosis. It has shown promise in improving liver health in conditions like nonalcoholic fatty liver disease (NAFLD) and is being explored for its effects on liver cirrhosis.
12389Eligibility Criteria
Adults aged 18-80 with cirrhosis due to cholestatic liver disease can join this trial. They must understand and sign consent, have a BMI of 18-48 kg/m2, and not be pregnant or breastfeeding. Participants need stable health, acceptable blood tests results (specific limits for liver enzymes, blood cells count), agree to use contraception, and cannot have other significant medical conditions or recent surgeries that could affect the study.Inclusion Criteria
Ability to comprehend and willingness to sign a written ICF for the study
I have liver cirrhosis due to bile duct disease and my condition's severity may change.
I am in good health with no significant medical issues found during recent checks.
+7 more
Exclusion Criteria
Human immunodeficiency virus (HIV) type 1 antibody positive at screening for all groups
My liver condition has changed significantly in the last month.
I frequently need fluid removed from my abdomen.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Saroglitazar Magnesium tablets once daily for 28 consecutive days
4 weeks
Daily administration with PK blood samples on Day 1 and Day 28
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 weeks
PK sample collection on Day 35 ±3 days
Open-label extension
Participants may continue receiving the study drug as part of the extension study
Participant Groups
The trial is testing two doses of Saroglitazar Magnesium (1 mg and 2 mg) in people with hepatic impairment caused by cholestatic liver diseases. It's an open-label extension study where everyone knows which treatment they're getting.
2Treatment groups
Experimental Treatment
Group I: Saroglitazar Magnesium 2 mgExperimental Treatment1 Intervention
The study drug will be administered from Day 1 to Day 28 once daily in the morning before breakfast without food.
Study drug -Saroglitazar Magnesium tablets: Dosage form- Tablets (immediate release); Dose- 2 mg/day; Frequency- One tablet per day (in the morning before breakfast without food); Duration- 28 consecutive days
Group II: Saroglitazar Magnesium 1 mgExperimental Treatment1 Intervention
The study drug will be administered from Day 1 to Day 28 once daily in the morning before breakfast without food.
Study drug -Saroglitazar Magnesium tablets; Dosage form- Tablets (immediate release); Dose- 1 mg/day; Frequency- One tablet per day (in the morning before breakfast without food); Duration of treatment- 28 consecutive days
Saroglitazar Magnesium is already approved in India for the following indications:
🇮🇳 Approved in India as Lipaglyn for:
- Type 2 diabetes mellitus
- Dyslipidemia
- Non-alcoholic fatty liver disease (NAFLD)
- Non-alcoholic steatohepatitis (NASH)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Zydus US002Indianapolis, IN
Indiana UniversityIndianapolis, IN
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Who Is Running the Clinical Trial?
Zydus Therapeutics Inc.Lead Sponsor
References
Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment. [2023]Saroglitazar magnesium, a dual peroxisome proliferator-activated receptor agonist, is under evaluation for treating various liver conditions. While the pharmacokinetics (PK) of saroglitazar have been extensively studied in diverse preclinical models and healthy subjects, a comprehensive assessment of its PK behavior under conditions of hepatic impairment is lacking. In this Phase 1, open-label, parallel-group study, the PK of a single dose of 4-mg saroglitazar magnesium was investigated in subjects having varying degrees of hepatic impairment with and without portal hypertension compared with appropriately matched individuals having normal hepatic function. Treatment-emergent adverse events for safety were also evaluated. Thirty-two subjects were enrolled in the hepatic-impaired groups and 23 subjects in the normal hepatic function group. Mild and moderate hepatic impairment did not significantly affect the PK of saroglitazar, compared with normal hepatic function. Although severe hepatic impairment did not alter maximum observed plasma concentration and half-life; saroglitazar exposure (area under the plasma concentration-time curve from time 0 to infinity) increased 3-fold, while the clearance was 61% lower compared to the subjects with normal hepatic function. This may require close monitoring or dose adjustments in individuals with severe hepatic impairment. A single oral dose of saroglitazar magnesium 4 mg was found to be safe and well tolerated in subjects with varying degrees of hepatic function.
Saroglitazar suppresses the hepatocellular carcinoma induced by intraperitoneal injection of diethylnitrosamine in C57BL/6 mice fed on choline deficient, l-amino acid- defined, high-fat diet. [2023]Saroglitazar is a novel PPAR-α/γ agonist with predominant PPAR-α activity. In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. In view of these observations, and the fact that NASH is a progressive disease leading to HCC, we hypothesized that saroglitazar may prevent the development of HCC in rodents.
Efficacy and safety of saroglitazar in real-world patients of non-alcoholic fatty liver disease with or without diabetes including compensated cirrhosis: A tertiary care center experience. [2023]Saroglitazar, a dual PPAR α/γ agonist, is useful in management of NAFLD and diabetic dyslipidemia. Here, we report the safety and efficacy of saroglitazar in NAFLD patients with or without diabetes including compensated cirrhosis.
Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. [2023]This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 4 mg saroglitazar treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).
Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models. [2021]Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common clinico-pathological conditions that affect millions of patients worldwide. In this study, the efficacy of saroglitazar, a novel PPARα/γ agonist, was assessed in models of NAFLD/NASH.
Saroglitazar in patients with non-alcoholic fatty liver disease and diabetic dyslipidemia: a prospective, observational, real world study. [2023]Saroglitazar, a dual peroxisome proliferator activated receptor α/γ agonist, approved for diabetic dyslipidemia (DD), is potential therapeutic option for non-alcoholic fatty liver disease (NAFLD). This prospective, observational, real-world study aimed to determine efficacy and safety of Saroglitazar in patients with NAFLD and DD. We included patients with DD and NAFLD who received Saroglitazar 4 mg once daily for 24 weeks. Blood investigations, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) (FibroScan) were compared at baseline and 24 weeks. Of 163 patients screened, 107 were included, and 101 completed 24 weeks treatment (mean age 50.4 ± 12.3 years, 78.5% males, mean body mass index 28.8 ± 4.2). After 24 weeks, alanine transaminase (ALT) reduced significantly from 94 (47-122) to 39 (31-49) (p
Effect of Food on the Pharmacokinetics of Saroglitazar Magnesium, a Novel Dual PPARαγ Agonist, in Healthy Adult Subjects. [2021]Label="BACKGROUND AND OBJECTIVE" NlmCategory="OBJECTIVE">Peroxisome proliferator-activated receptors (PPARs) have recently become a focus of interest for their important roles in glucose and lipid metabolism. In humans, PPARα activation causes a decrease in plasma triglyceride (TG) levels, enhancement of high-density lipoprotein cholesterol (HDL-C) and simultaneous enhancement of very-low-density lipoprotein (VLDL) lipolysis, whereas PPARγ agonists act as insulin sensitizers and improve insulin resistance, which is very useful in patients with type 2 diabetes mellitus (T2DM). Saroglitazar magnesium is a dual PPAR agonist with potent predominant PPARα and moderate PPARγ activity and the first glitazar to be granted marketing authorization in India. This study was conducted to evaluate the oral bioavailability and safety and tolerability of a Lipaglyn™ (saroglitazar magnesium) 4-mg tablet in healthy, adult human subjects under fed relative to fasting conditions.
Saroglitazar improves nonalcoholic fatty liver disease and metabolic health in liver transplant recipients. [2023]NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor α/γ agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter ≥264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3±10.5% at baseline to 8.1±7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.
Saroglitazar for Nonalcoholic Fatty Liver Disease: A Single Centre Experience in 91 Patients. [2023]Saroglitazar is a novel, dual peroxisome proliferator-activated receptors-α/γ agonist and is being investigated for the treatment of nonalcoholic fatty liver disease (NAFLD).