Hepatic Impairment, Cholestatic Liver Disease, & NASH with Advanced Fibrosis & Normal Hepatic Function

NCT04469920 | Completed Phase 1 FDA Drug

• 1 other identifier: SARO.19.003
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 2

Brief Summary

This will be a Phase 1, Open-label Study of Participants with Hepatic Impairment, Cholestatic Liver Disease, and NASH with Advanced Fibrosis and Normal Hepatic Function

Conditions

Hepatic Impairment

Outcome Measures

Primary Outcomes (7)

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

  The area under the plasma concentration versus time curve from zero to infinity will be calculated by adding Ct/Kel to AUCt, where Ct is the last quantifiable concentration and Kel is the elimination rate constant.

  Before dosing on Day 1 through Day 7

• AUC from time zero to the last quantifiable concentration (AUC0-t)

  The area under the plasma concentration versus time curve will be calculated using the linear trapezoidal rule from the zero time point to the last quantifiable concentration.

  Before dosing on Day 1 through Day 7

• Cmax

  Maximum measured plasma concentration over the time span specified.

  Before dosing on Day 1 through Day 7

• Tmax

  Time of the maximum measured plasma concentration.

  Before dosing on Day 1 through Day 7

• t1/2

  The half-life will be calculated by the equation tHalf = 0.693/ Kel. Kel (The terminal elimination rate constant) will be obtained from the slope of the line, fitted by linear least squares regression, through the terminal points of the natural log of the concentration versus time plot for these points

  Before dosing on Day 1 through Day 7

• CL/F

  Clearance

  Before dosing on Day 1 through Day 7

• Vz/F

  Volume of distribution

  Before dosing on Day 1 through Day 7

Secondary Outcomes (4)

• Urine Pharmacokinetic: Ae

  Before dosing on Day 1 through Day 5

• Incidence of AEs

  Before dosing on Day 1 through Day 12

• Unbound Fraction

  Day 1

• Unbound concentration

  Day 1

Study Arms (7)

Group 1- mild hepatic impairment without evidence of PHT

EXPERIMENTAL

Subject with mild hepatic impairment without evidence of portal hypertension (PHT) based on Class A CPT score 5-6 points

Drug: Saroglitazar Magnesium 4 mg

Group 2- mild hepatic impairment with evidence of PHT

EXPERIMENTAL

Subjects with mild hepatic impairment with evidence of portal hypertension based on Class A CPT score 5-6 points

Drug: Saroglitazar Magnesium 4 mg

Group 3-moderate hepatic impairment

EXPERIMENTAL

Subjects with moderate hepatic impairment based on Class B CPT score 7-9 points

Drug: Saroglitazar Magnesium 4 mg

Group 4- severe hepatic impairment

EXPERIMENTAL

Subjects with severe hepatic impairment based on Class C CPT score 10-14 points)

Drug: Saroglitazar Magnesium 4 mg

Group 5-cholestatic liver disease

EXPERIMENTAL

Subjects with cholestatic liver disease

Drug: Saroglitazar Magnesium 2 mg; Drug: Saroglitazar Magnesium 4 mg

Group 6-Non-cirrhotic Advanced Fibrosis secondary to NASH

EXPERIMENTAL

Subjects with Non-cirrhotic Advanced Fibrosis secondary to NASH

Drug: Saroglitazar Magnesium 2 mg; Drug: Saroglitazar Magnesium 4 mg

Group 7- normal hepatic function

EXPERIMENTAL

Subjects with normal hepatic function

Drug: Saroglitazar Magnesium 2 mg; Drug: Saroglitazar Magnesium 4 mg

Interventions

Saroglitazar Magnesium 2 mg DRUG

1 tablet, single dose at Day 1

Also known as: Not any

Group 5-cholestatic liver disease; Group 6-Non-cirrhotic Advanced Fibrosis secondary to NASH; Group 7- normal hepatic function

Saroglitazar Magnesium 4 mg DRUG

1 tablet, single dose at Day 1

Also known as: Not any

Group 1- mild hepatic impairment without evidence of PHT; Group 2- mild hepatic impairment with evidence of PHT; Group 3-moderate hepatic impairment; Group 4- severe hepatic impairment; Group 5-cholestatic liver disease; Group 6-Non-cirrhotic Advanced Fibrosis secondary to NASH; Group 7- normal hepatic function

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to comprehend and willingness to sign a written informed consent for the study.
• Male or female aged 18 to 80 years (inclusive) at the time of signing the ICF.
• Body mass index within the range 18.0 to 48.0 kg/m2 (inclusive) at screening.
• Females must be non-pregnant, non-lactating and of non-childbearing potential or using highly efficient contraception for the full duration of the study.
• Females of child-bearing potential and Males must agree to use contraception for the full duration of the study.
• Ability to swallow and retain oral medication.
• Groups 1 through 6 subjects may have medical findings consistent with their degree of hepatic dysfunction, as determined by medical history, physical examination, vital signs, ECGs, and clinical laboratory examinations at screening and check-in. Participants with abnormal findings considered not clinically significant by the Investigator are eligible.
• Participants with hepatic impairment in Groups 1-4 will be classified at screening based on CPT score. If the hepatic impairment classification for the subject is not the same at screening and day -1, enrolment of the subject into a hepatic category group will be at the discretion of the hepatology Investigator.
• Laboratory test values for Groups 1-4 hepatic impairment subjects must be clinically acceptable to the Investigator and meet all of the following parameters at Screening:
• ALT/AST value ≤ 10 × upper limit of normal (ULN)
• Absolute neutrophil count (ANC) ≥ 750/mm3
• Platelets ≥ 25,000/mm3
• Hemoglobin ≥ 8 g/dL
• α-fetoprotein \< 50 ng/mL or 50-80 ng/mL with concurrent negative imaging study (US, CT, MRI)
• Group 2 must have evidence of PHT as manifested by one of the following:

You may not qualify if:

• Any significant, unstable medical condition or other instability that would prevent the subject from participating in the study as determined by the Investigator or designee.
• History of malignancy of any type in the last 3 years of screening, with the exception of the following: in situ cervical or breast cancer or surgically excised non-melanoma skin cancers (i.e. basal cell or squamous cell carcinoma).
• History of stomach or intestinal surgery or resection within the six months prior to screening that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed).
• History of any significant drug allergy (such as anaphylaxis) deemed clinically relevant by the Investigator.
• Any major surgery within 3 months of screening.
• Donation of blood or blood products within 3 months prior to screening.
• Current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment or symptoms of active infectious disease within the two weeks prior to screening.
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, within 21 days prior to screening, unless deemed acceptable by the Investigator.
• Receiving or has received any investigational drug within the 30 days or 5 halflives (whichever is longer), before receiving Saroglitazar Magnesium.
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2 by modification of diet in renal disease (MDRD) formula at screening.
• Positive alcohol breath test at the time of check-in or those subjects who have current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance or subject safety.
• Positive test for drugs of abuse at screening or admission.
• Any subject with poor peripheral venous access
• Receipt of blood products within 1 month prior to check in.
• Human immunodeficiency virus (HIV) type 1 antibody positive at screening for all groups.

Sponsors & Collaborators

• Zydus Therapeutics Inc.: lead

Study Sites (2)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

American Research Corporation at Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Interventions

saroglitazar

Study Officials

• Deven Parmar, MD

  Zydus Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2020
• First Posted: July 14, 2020
• Study Start: July 16, 2020
• Primary Completion: March 21, 2022
• Study Completion: March 21, 2022
• Last Updated: September 20, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)