Overview

Hepatic Impairment With Cirrhosis Due to Cholestatic Liver Disease

Status:
Recruiting
Trial end date:
2022-05-01
Target enrollment:
0
Participant gender:
All
Summary
A Phase 1, Open-label Extension Groups Study in Subjects having Hepatic Impairment with Cirrhosis due to Cholestatic Liver Disease
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
Zydus Therapeutics Inc.
Criteria
Inclusion Criteria:

For all subjects:

1. Ability to comprehend and willingness to sign a written ICF for the study.

2. Male or female aged 18 to 80 years (inclusive) at the time of signing the ICF.

3. Body mass index within the range 18.0 to 48.0 kg/m2 (inclusive) at screening.

4. Females must be non-pregnant, non-lactating and of non-childbearing potential or using
highly efficient contraception for the full duration of the study.

5. Females of child-bearing potential and males must agree to use contraception for the
full duration of the study.

6. Ability to swallow and retain oral medication.

For Subjects in Groups 8 and 9 (Hepatic impairment group but with cirrhosis from
cholestatic liver disease):

7. Participants having documented history of hepatic impairment with cirrhosis due to
cholestatic liver disease in Groups 8 and 9 will be classified in sub groups 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.

8. Laboratory test values for hepatic impairment subjects Groups 8 (8A, 8B, 8C) and 9
(9A, 9B, 9C) must be clinically acceptable to the Investigator and meet all the
following parameters at Screening:

1. ALT/AST value ≤ 10 × upper limit of normal (ULN)

2. Absolute neutrophil count (ANC) ≥ 750/mm3

3. Platelets ≥ 25,000/mm3

4. Hemoglobin ≥ 8 g/dL

5. α-fetoprotein < 50 ng/mL or 50-80 ng/mL with negative imaging study (US, CT,
MRI).

For Subjects in Groups 8D and 9D (normal hepatic function groups):

9. Subjects should be in good health as determined by no clinically significant findings
in the medical history, physical examination, vital signs, 12-lead electrocardiograms
(ECGs), or laboratory examinations at Screening or Check-in.

10. Laboratory test values within normal limits or considered not clinically significant
by the Investigator for subjects with normal hepatic function including ALT/AST < 1.2
× ULN at screening.

Exclusion Criteria:

For all subjects:

1. 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.

2. 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).

3. 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).

4. History of any significant drug allergy (such as anaphylaxis) deemed clinically
relevant by the Investigator.

5. Any major surgery within 3 months of screening.

6. Donation of blood or blood products within 3 months prior to screening.

7. Current active infectious disease requiring systemic antibiotic, antifungal, or
antiviral treatment or symptoms of active infectious disease within the two weeks
prior to screening.

8. 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.

9. Receiving or has received any investigational drug within the 30 days or 5 half-lives
(whichever is longer), before receiving Saroglitazar Magnesium.

10. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 by modification of diet
in renal disease (MDRD) formula at screening.

11. 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.

12. Positive test for drugs of abuse at screening or admission. Subjects with a positive
test based on a prescribed medication may be enrolled.

13. Any subject with poor peripheral venous access

14. Receipt of blood products within 1 month prior to check in.

15. Human immunodeficiency virus (HIV) type 1 antibody positive at screening for all
groups.

For Subjects in Groups 8 and 9 (Hepatic impairment group but with cirrhosis from
cholestatic liver disease):

16. Other known cause of liver disease such as NASH, alcoholic steatohepatitis (ASH),
autoimmune hepatitis, or acute or chronic viral hepatitis as determined by the
Investigator and subject's medical records.

17. Subjects who have had a change in hepatic disease status within 30 days of screening,
as documented by the participant's medical history and deemed clinically significant
by the Investigator.

18. Subjects having -

1. History of gastrointestinal bleeding within 1 month prior to screening.

2. Current functioning organ transplant.

3. Evidence of severe ascites requiring frequent paracentesis in the opinion of
investigator.

19. Subjects who use or intend to use any over the counter (vitamins, minerals, and
phytotherapeutic/herbal/plant-derived preparations) or prescription medications within
30 days or 5 half-lives (whichever is longer) prior to enrolment, with the exception
of hormone replacement therapy and therapies for hepatic disease and treatments of
associated disorders that have been stable for at least 30 days prior to screening and
until Day 1, unless deemed acceptable by the Investigator (or designee).

For Control with Normal Hepatic Function:

20. Subjects who have taken any prescription medications or over-the-counter medications,
including herbal products, within 14 days prior to start of study drug dosing, with
the exception of vitamins, acetaminophen, hormonal contraceptive medications and/or
any other over-the-counter product approved by the Investigator.