Saroglitazar for Kidney Failure

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

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Saroglitazar Magnesium, a medication that helps control blood sugar and fat levels, in people with severe kidney problems and those with normal kidney function.

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 Saroglitazar safe for human use?

Saroglitazar has been studied in various clinical trials and found to be generally safe and well-tolerated in humans, including those with type 2 diabetes and liver conditions. No serious adverse events were reported, and it was well-tolerated even in individuals with different levels of liver function. ^{1 2 3 4 5}

What makes the drug Saroglitazar Magnesium unique for treating kidney failure?

Saroglitazar Magnesium is unique because it is designed to target both lipid and glucose metabolism, which may be beneficial for patients with kidney failure who often have issues with both. Unlike some other treatments, it may offer a dual benefit by addressing both blood sugar and cholesterol levels, potentially reducing the need for multiple medications. ^{6 7 8 9 10}

Research Team

Deven Parmar, MD

Principal Investigator

Zydus Therapeutics Inc.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A multicenter, prospective, randomized, double-blind study to evaluate the safety and efficacy of Saroglitazar 2 and 4 mg compared with placebo in type 2 diabetes mellitus patients having hypertriglyceridemia not controlled with atorvastatin therapy (PRESS VI). [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety Evaluation of Single-Dose Saroglitazar Magnesium in Subjects with Hepatic Impairment. [2023]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The first approved agent in the Glitazar's Class: Saroglitazar. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of Food on the Pharmacokinetics of Saroglitazar Magnesium, a Novel Dual PPARαγ Agonist, in Healthy Adult Subjects. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A Multicenter, Prospective, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Saroglitazar 2 and 4 mg Compared to Pioglitazone 45 mg in Diabetic Dyslipidemia (PRESS V). [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Treating type 2 diabetes in renal insufficiency: the role of pioglitazone. [2019]

7. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of pioglitazone in patients with impaired renal function. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Combination therapy of pioglitazone with voglibose improves glycemic control safely and rapidly in Japanese type 2-diabetic patients on hemodialysis. [2022]

9. Hungary pubmed.ncbi.nlm.nih.gov

[Oral antidiabetic drugs in chronic renal disease]. [2018]

10. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy of pioglitazone on type 2 diabetic patients with hemodialysis. [2022]