Study to Evaluate Absorption, Metabolism and Excretion of Single-dose [14C]-Saroglitazar in Healthy Male Subjects

NCT04112446 | Completed Phase 1 FDA Drug

• 1 other identifier: SARO.19.002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a Phase I, open-label, nonrandomized, single-dose study in healthy male subjects.

Conditions

Healthy

Outcome Measures

Primary Outcomes (13)

• AUC from time zero to infinity (AUC0-∞)

  Area under the time curve from time zero to infinity will be calculated for saroglitazar and saroglitazar sulfoxide in plasma, and total radioactivity in whole blood and plasma

  At predose to maximum up to Day 12

• AUC from time zero to the last quantifiable concentration (AUC0-t) administration of [14C]-saroglitazar magnesium

  Area under the time curve from time zero to the last quantifiable concentration will be calculated for saroglitazar and saroglitazar sulfoxide in plasma, and total radioactivity in whole blood and plasma

  At predose to maximum up to Day 12

• Cmax

  Maximum observed concentration will be calculated for saroglitazar and saroglitazar sulfoxide in plasma, and total radioactivity in whole blood and plasma

  At predose to maximum up to Day 12

• Tmax

  Time to reach maximum observed concentration will be calculated for saroglitazar and saroglitazar sulfoxide in plasma, and total radioactivity in whole blood and plasma

  At predose to maximum up to Day 12

• t1/2

  Apparent terminal elimination half-life will be calculated for saroglitazar and saroglitazar sulfoxide in plasma, and total radioactivity in whole blood and plasma

  At predose to maximum up to Day 12

• Apparent total clearance (CL/F)

  The apparent total clearance (CL/F) will be determined for saroglitazar

  At predose to maximum up to Day 12

• Apparent volume of distribution (Vz/F) during the terminal elimination phase

  The Apparent volume of distribution (Vz/F) during the terminal elimination phase will be determined for saroglitazar

  At predose to maximum up to Day 12

• AUC0-∞ of plasma saroglitazar relative to AUC0-∞ of plasma total radioactivity (AUC0-∞ Plasma saroglitazar/Total Radioactivity Ratio)

  AUC0-∞ of plasma saroglitazar relative to AUC0-∞ of plasma total radioactivity (AUC0-∞ Plasma saroglitazar/Total Radioactivity Ratio) will be calculated

  At predose to maximum up to Day 12

• AUC0-∞ of whole blood total radioactivity to AUC0-∞ of plasma total radioactivity (AUC0 ∞ Blood/Plasma Ratio)

  AUC0-∞ of whole blood total radioactivity to AUC0-∞ of plasma total radioactivity (AUC0 ∞ Blood/Plasma Ratio) will be calculated

  At predose to maximum up to Day 12

• Mean residence time

  Mean residence time for saroglitazar and saroglitazar sulfoxide will be calculated

  At predose to maximum up to Day 12

• Total radioactivity amount excreted in urine and feces

  Amount of radioactivity excreted in urine and Feces will be calculated.

  At predose to maximum up to Day 12

• Percentage radioactivity excreted in urine and feces

  Percentage radioactivity excreted in urine and Feces will be calculated.

  At predose to maximum up to Day 12

• Renal clearance (CLR)

  Renal clearance for saroglitazar and saroglitazar sulfoxide will be determined

  At predose to maximum up to Day 12

Secondary Outcomes (2)

• Metabolic profile/ identifications of metabolites and probable structure elucidation for saroglitazar in plasma, urine, and feces

  Maximum up to Day 12

• Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

  Maximum up to Day 12

Other Outcomes (2)

• Amount of Saroglitazar excreted in feces

  At predose to maximum up to Day 12

• Percentage of Saroglitazar excreted in feces

  At predose to maximum up to Day 12

Study Arms (1)

Study Treatment

EXPERIMENTAL

4 mg \[14C\]-saroglitazar magnesium (approximately 100 μCi) oral suspension

Drug: Saroglitazar magnesium

Interventions

Saroglitazar magnesium DRUG

On Day 1, subjects will receive a single oral dose of \[14C\]-saroglitazar magnesium

Also known as: not any

Study Treatment

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males, of any race, between 18 and 55 years of age, inclusive.
• Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations at Screening and/or Check-in as assessed by the Investigator (or designee).
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
• History of a minimum of 1 bowel movement per day.

You may not qualify if:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• Known hypersensitivity to either saroglitazar magnesium or other PPAR agonists, and/or the excipients in the saroglitazar magnesium formulation.
• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed). History of cholecystectomy will not be allowed.
• Subjects with congenital nonhemolytic hyperbilirubinemia (eg, suspicion of Gilbert's syndrome based on total and direct bilirubin).
• History of alcoholism or drug/chemical abuse within 1 year prior to Check-in.
• Alcohol consumption of \> 14 units per week. One unit of alcohol equals 12 oz (360 mL) of beer, 1½ oz (45 mL) of liquor, or 5 oz (150 mL) of wine.
• Positive urine drug screen at Screening or positive alcohol breath test result or positive urine drug screen at Check-in.
• Positive hepatitis panel and/or positive human immunodeficiency virus test ( Appendix 2).
• Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing or 5 times the t1/2 (whichever is longer).
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
• Use or intend to use any prescription medications/products within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
• Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
• Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
• Use of tobacco- or nicotine-containing products within 3 months prior to Check-in, or positive cotinine at Screening or Check-in.

Sponsors & Collaborators

• Zydus Therapeutics Inc.: lead

Study Sites (1)

Covance Clinical Research Unit Inc.

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

saroglitazar

Study Officials

• John E. Blanchard, MD

  Covance

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: October 2, 2019
• Study Start: September 20, 2019
• Primary Completion: October 29, 2019
• Study Completion: October 29, 2019
• Last Updated: November 13, 2019

Record last verified: 2019-11

Locations

US (1)