Clinical trial NCT04112446: Study to Evaluate Absorption, Metabolism and Excretion of Single-dose [14C]-Saroglitazar in Healthy Male Subjects
Official title: A Phase I, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-Saroglitazar Following a Single Oral Dose of [14C]-Saroglitazar Magnesium in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Zydus Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-02
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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

Detailed description: Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the dose administration. Subjects will be admitted into the Clinical Research Unit (CRU) on Day -1 and be confined to the CRU until at least Day 8. On Day 1, subjects will receive a single oral dose of \[14C\]-saroglitazar magnesium. Subjects will be discharged if the following discharge criteria are met: plasma radioactivity levels below the limit of quantitation for 2 consecutive collections and ≥ 90% mass balance recovery, or ≤ 1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 3 consecutive 24-hour periods in which both are collected. If discharge criteria are not met by Day 8, subjects will remain in the CRU up to Day 12.

Eligibility criteria: Inclusion Criteria:

1. Males, of any race, between 18 and 55 years of age, inclusive.
2. Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
3. 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).
4. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
5. History of a minimum of 1 bowel movement per day.

Exclusion Criteria:

1. 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).
2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
3. Known hypersensitivity to either saroglitazar magnesium or other PPAR agonists, and/or the excipients in the saroglitazar magnesium formulation.
4. 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.
5. Subjects with congenital nonhemolytic hyperbilirubinemia (eg, suspicion of Gilbert's syndrome based on total and direct bilirubin).
6. History of alcoholism or drug/chemical abuse within 1 year prior to Check-in.
7. 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.
8. Positive urine drug screen at Screening or positive alcohol breath test result or positive urine drug screen at Check-in.
9. Positive hepatitis panel and/or positive human immunodeficiency virus test ( Appendix 2).
10. 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).
11. 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).
12. Use or intend to use any prescription medications/products within 14 days prior to Check-in, unless deemed acceptable by the Investigator (or designee).
13. 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).
14. 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).
15. Use of tobacco- or nicotine-containing products within 3 months prior to Check-in, or positive cotinine at Screening or Check-in.
16. Receipt of blood products within 2 months prior to Check-in.
17. Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
18. Poor peripheral venous access.
19. Have previously completed or withdrawn from this study or any other study investigating saroglitazar magnesium, and have previously received the investigational product.
20. Subjects with exposure to significant diagnostic or therapeutic radiation (eg, serial X-ray, computed tomography scan, barium meal) or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in.
21. Subjects who have participated in a radiolabeled drug study where exposures are known to the Investigator within the previous 4 months prior to admission to the clinic for this study or participated in a radiolabeled drug study where exposures are not known to the Investigator within the previous 6 months prior to admission to the clinic for this study. The total 12-month exposure from this study and a maximum of 2 other previous radiolabeled studies within 4 to 12 months prior to this study will be within the Code of Federal Regulations (CFR) recommended levels considered safe, per United States (US) Title 21 CFR 361.1: less than 5,000 mrem whole-body annual exposure with consideration given to the half-lives of the previous radiolabeled study drugs received.
22. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.

Primary outcomes:
measure: AUC from time zero to infinity (AUC0-∞)
timeFrame: At predose to maximum up to Day 12
measure: AUC from time zero to the last quantifiable concentration (AUC0-t) administration of [14C]-saroglitazar magnesium
timeFrame: At predose to maximum up to Day 12
measure: Cmax
timeFrame: At predose to maximum up to Day 12
measure: Tmax
timeFrame: At predose to maximum up to Day 12
measure: t1/2
timeFrame: At predose to maximum up to Day 12
measure: Apparent total clearance (CL/F)
timeFrame: At predose to maximum up to Day 12
measure: Apparent volume of distribution (Vz/F) during the terminal elimination phase
timeFrame: At predose to maximum up to Day 12
measure: AUC0-∞ of plasma saroglitazar relative to AUC0-∞ of plasma total radioactivity (AUC0-∞ Plasma saroglitazar/Total Radioactivity Ratio)
timeFrame: At predose to maximum up to Day 12
measure: AUC0-∞ of whole blood total radioactivity to AUC0-∞ of plasma total radioactivity (AUC0 ∞ Blood/Plasma Ratio)
timeFrame: At predose to maximum up to Day 12
measure: Mean residence time
timeFrame: At predose to maximum up to Day 12
measure: Total radioactivity amount excreted in urine and feces
timeFrame: At predose to maximum up to Day 12
measure: Percentage radioactivity excreted in urine and feces
timeFrame: At predose to maximum up to Day 12
measure: Renal clearance (CLR)
timeFrame: At predose to maximum up to Day 12
Secondary outcomes:
measure: Metabolic profile/ identifications of metabolites and probable structure elucidation for saroglitazar in plasma, urine, and feces
timeFrame: Maximum up to Day 12
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Maximum up to Day 12
Other outcomes:
measure: Amount of Saroglitazar excreted in feces
timeFrame: At predose to maximum up to Day 12
measure: Percentage of Saroglitazar excreted in feces
timeFrame: At predose to maximum up to Day 12
Locations:
city: Madison
country: United States
facility: Covance Clinical Research Unit Inc.
state: Wisconsin
Study officials:
affiliation: Covance
name: John E. Blanchard, MD
role: PRINCIPAL_INVESTIGATOR
References: