Saroglitazar for Kidney Failure

No longer recruiting at 3 trial locations

Overseen By Farheen A. Shaikh

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Zydus Therapeutics Inc.

Must not be taking: Antibiotics, Antifungals, Antivirals, others

Disqualifiers: Malignancy, Liver disease, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of Saroglitazar Magnesium on individuals with various kidney conditions. The researchers aim to study its safety and efficacy in people with either normal kidney function or severe kidney impairment. Participants will be divided into groups based on kidney health to receive different doses of the treatment. This trial suits those with severe kidney issues not on dialysis or those with normal kidney function who are otherwise healthy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

Participants with severe renal impairment must stop using over-the-counter or prescription medications 30 days before the trial, except for stable therapies for renal disease. Those with normal renal function must stop taking prescription or over-the-counter medications 14 days before the trial, except for certain approved products.

Is there any evidence suggesting that Saroglitazar Magnesium is likely to be safe for humans?

Research shows that saroglitazar magnesium is generally safe and well-tolerated. Studies have found that even at high doses, up to 128 mg in a single dose, it did not cause major side effects. Another study demonstrated its tolerability in people with varying liver and kidney function, including severe kidney issues.

In a study with 55 participants, saroglitazar magnesium proved safe for those with liver problems, suggesting safety even when liver function is compromised. For individuals with severe kidney problems, the treatment was also considered safe.

Overall, this evidence supports that saroglitazar magnesium is well-tolerated in various conditions. However, as this is a Phase 1 trial, the primary goal is to further assess safety, so participants will be closely monitored. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney failure?

Saroglitazar Magnesium is unique for treating kidney failure because it offers a new mechanism of action. Unlike current treatments that primarily focus on managing symptoms or slowing progression, Saroglitazar Magnesium acts as a dual PPAR alpha/gamma agonist. This dual action helps improve lipid and glucose metabolism, which might offer better control over underlying metabolic disturbances contributing to kidney failure. Researchers are excited about its potential to provide a more comprehensive approach to managing kidney health by targeting both lipid and glucose levels in patients.

What evidence suggests that Saroglitazar might be an effective treatment for kidney failure?

Research has shown that Saroglitazar Magnesium holds promise for treating kidney conditions. It targets specific body parts to reduce inflammation and improve energy processing. Earlier studies demonstrated that Saroglitazar effectively enhances liver and kidney function and is safe for individuals with liver issues. No major side effects were reported, and it also helped control blood sugar levels. In this trial, participants will receive either a 2 mg or 4 mg dose of Saroglitazar Magnesium, depending on their group assignment. These findings suggest it could be a helpful treatment for people with serious kidney problems. ^{1 2 5 6 7}

Who Is on the Research Team?

Deven Parmar, MD

Principal Investigator

Zydus Therapeutics Inc.

Are You a Good Fit for This Trial?

Adults aged 18-80 with either normal kidney function or severe renal impairment (not on dialysis, eGFR <30) can join. They must be able to take oral meds, have a BMI of 18-48 kg/m2, and use effective contraception if applicable. Exclusions include unstable medical conditions, recent malignancies except certain cancers, drug/alcohol abuse, HIV/HBV/HCV infection, major surgeries within specific timeframes.

Inclusion Criteria

Your body mass index (BMI) is between 18.0 and 48.0.

I can swallow and keep down pills.

My kidney function, measured by eGFR, has been checked for changes.

Exclusion Criteria

I have not had a kidney removal or transplant, recent dialysis, or significant lab result issues.

I haven't had major stomach or intestinal surgery in the last 6 months.

My heart's electrical activity is within a safe range, confirmed by tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Saroglitazar Magnesium, with dosing based on renal function group

1 day

1 visit (in-person)

Pharmacokinetic Monitoring

Participants are monitored for pharmacokinetic parameters and safety, including volume of distribution, clearance, and maximum plasma concentration

7 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Saroglitazar Magnesium

Trial Overview The study is testing Saroglitazar Magnesium's effects in people with different levels of kidney health. It's an open-label Phase 1 trial where participants are openly given the medication to understand how it behaves in bodies with normal vs severely impaired kidneys.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 1 Intervention

Subjects (Normal renal function eGFR ≥90) will be matched according to age (± 10 years), sex, and weight (± 20 kg) with participants in Group 1 (Severe renal impairment not on HD) on a one to one basis based on demographic characteristic. Here, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium.

Group II: Group 1 Experimental Treatment 1 Intervention

Subjects in severe renal impairment group will be enrolled and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by another 8 subjects who will receive 4 mg dose).

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)

Who Is Running the Clinical Trial?

Zydus Therapeutics Inc.

Lead Sponsor

Trials

16

Recruited

1,100+

Published Research Related to This Trial

In a study involving 27 participants with varying degrees of renal function, pioglitazone was found to be well tolerated across all groups, indicating its safety in patients with renal impairment.

While patients with severe renal impairment showed increased serum concentrations of pioglitazone and its metabolites, the pharmacokinetic profiles were not significantly different from those with normal or moderate renal function, suggesting that dose adjustments may not be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of pioglitazone in patients with impaired renal function. Budde, K., Neumayer, HH., Fritsche, L., et al.[2019]

Saroglitazar magnesium, a dual PPAR agonist, was found to be well tolerated in a study of 54 healthy adults, with only mild adverse events reported, indicating its safety for use.

While food intake reduced the maximum concentration (C max) of saroglitazar by 30%, it did not affect the overall absorption (AUC∞), suggesting that the drug's therapeutic efficacy remains intact regardless of food intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Food on the Pharmacokinetics of Saroglitazar Magnesium, a Novel Dual PPARαγ Agonist, in Healthy Adult Subjects. Patel, MR., Kansagra, KA., Parikh, DP., et al.[2021]

In a Phase 1 study involving 55 subjects, saroglitazar magnesium was found to be safe and well tolerated across varying degrees of hepatic impairment, indicating its potential for treating liver conditions.

While mild and moderate hepatic impairment did not significantly affect the drug's pharmacokinetics, severe hepatic impairment led to a threefold increase in drug exposure, suggesting that careful monitoring or dose adjustments may be necessary for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment. Lawitz, E., Parmar, D., Momin, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04446507

A Pharmacokinetic Study of Saroglitazar Magnesium in ... A Pharmacokinetic Study of Saroglitazar Magnesium in Subjects with Severe Renal Impairment and Normal Renal Function. ClinicalTrials.gov ID NCT04446507. Sponsor ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12395119/

Evaluation of Effectiveness and Tolerability of Saroglitazar in ... No significant adverse events and renal impairment were observed. Conclusion. Saroglitazar demonstrated significant improvements in glycemic ...

3. withpower.com withpower.com/trial/phase-1-renal-insufficiency-6-2020-fd89e

Saroglitazar for Kidney Failure · Info for Participants In a Phase 1 study involving 55 subjects, saroglitazar magnesium was found to be safe and well tolerated across varying degrees of hepatic impairment, ...

4. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3450?af=R

Pharmacokinetic, Safety, and Pharmacodynamic Profiles of ... Saroglitazar magnesium (2 and 4 mg oral doses) was previously demonstrated to be safe and efficacious in patients with PBC. However, at 4 mg ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1567576923000115

Saroglitazar, a dual PPAR-α/γ agonist, alleviates LPS ... This study highlights saroglitazar (SAR), a dual PPAR-α/γ agonist, as a proposed prophylactic drug against LPS-induced hepatic-renal injury.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4403747/

Saroglitazar for the treatment of hypertrig-lyceridemia in ... Saroglitazar was safe and well-tolerated up to 128 mg, as a single dose, and up to 8 mg once per day for up to 10 days. Saroglitazar did not show any clinically ...

7. link.springer.com link.springer.com/article/10.1007/s40261-022-01244-5

“Efficacy and Safety of Saroglitazar in Patients with ... Our recent study did not find renal safety by considering serum creatinine levels but it has provided evidence that saroglitazar can be used as ...