Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Mg in Patients With Primary Biliary Cholangitis

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2024
• Main ID: NCT03112681
• Date of registration: 10/04/2017
• Prospective Registration: Yes
• Primary sponsor: Zydus Therapeutics Inc.
• Public title: Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Mg in Patients With Primary Biliary Cholangitis EPICS
• Scientific title: A Phase 2, Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability and Efficacy of Saroglitazar Magnesium in Patients With Primary Biliary Cholangitis (EPICS )
• Date of first enrolment: August 18, 2017
• Target sample size: 37
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03112681
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Deven Parmar, MD FACP FCP
• Affiliation: Zydus Therapeutics Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Males or females, between 18 and 75 years of age, inclusive.

2. a) Patients on therapeutic doses of Ursodeoxycholic acid (UDCA) for =12 months and
stable therapy for =3 months prior to enrolment.

OR b) Patients who are unable to tolerate UDCA, and did not receive UDCA for at least
3 months from the date of screening.

3. History of confirmed Primary Biliary Cholangitis Diagnosis, based on American
Association for the Study of Liver Disease [AASLD] and European Association for Study
of the Liver [EASL] Practice Guidelines; [Lindor 2009; EASL 2009], as demonstrated by
the presence of at least=2 of the following 3 diagnostic factors:

- History of elevated Alkaline Phosphatase levels for at least 6 months prior to
Screening Visit 1

- Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low
titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or
antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid
dehydrogenase complex])

- Liver biopsy consistent with PBC.

4. ALP =1.67x upper limit of normal (ULN) at Visit 1 and Visit 2 and with < 30% variance
between the levels from Visit 1 to Visit 2.

5. Contraception: Female patients must be postmenopausal, surgically sterile, or if
premenopausal, agree to use = 1 effective method of contraception during the trial.
Effective methods of contraception are considered to be Hormonal (e.g., contraceptive
pill, patch, intramuscular implant or injection); or Double barrier method, i.e., (a)
condom (male or female) or (b) diaphragm, with spermicide; or Intrauterine device
(IUD); or Vasectomy (partner).

6. Must provide written informed consent and agree to comply with the trial protocol.

Exclusion Criteria:

1. Consumption of >3 units of alcohol per day (>21 units per week) if male and >2 units
of alcohol per day (>14 units per week) if female for at least 3 consecutive months in
the last 5 years (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of
spirits/hard liquor).

2. History or presence of other concomitant liver diseases including:

- Hepatitis B or C virus (HCV, HBV) infection

- Primary sclerosing cholangitis (PSC)

- Alcoholic liver disease

- Definite autoimmune liver disease or overlap syndrome

- Non-alcoholic steatohepatitis (NASH)

3. Cirrhosis with complications, including history or presence of: spontaneous bacterial
peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN, ascites, encephalopathy,
known esophageal varices or history of variceal bleeding and active or history of
hepatorenal syndrome.

4. History of any venous thromboembolism, TIA, intracranial hemorrhage, neoplasm,
arteriovenous malformation, vasculitis, bleeding disorder, coagulation disorders or
screening blood tests that indicate altered coagulability (e.g. platelet count, aPTT,
PTT or TT tests).

5. Patients with INR > ULN at visit 1.

6. Patients with total bilirubin > ULN at visit 1 that is not due to Gilbert's syndrome

7. Patients with >30% increase in ALT, total bilirubin, or INR between Visit 1 to Visit
2.

8. Patients with serum creatinine >ULN according to the gender at Visit 1.

9. Patients with abnormal total creatine kinase (CK) OR lipase OR amylase at Visit 1.

10. Unstable cardiovascular disease, including:

- unstable angina, (i.e., new or worsening symptoms of coronary heart disease
within the past 3 months), acute coronary syndrome within the past 6 months,
acute myocardial infarction in the past 3 months or heart failure of New York
Heart Association class (III - IV) or worsening congestive heart failure, or
coronary artery intervention, within the past 6 months

- history of (within prior 3 months) or current unstable cardiac dysrhythmias

- uncontrolled hypertension (systolic blood pressure [BP] >160 mmHg and/or
diastolic BP >100 mmHg)

- stroke or transient ischemic attack within the prior 6 months

11. History of malignancy in the past 5 years and/or active neoplasm with the exception of
resolved superficial nonmelanoma skin cancer.

12. Contraindications to Saroglitazar magnesium or has any conditions affecting the
ability to evaluate the effects of Saroglitazar magnesium.

13. Known allergy, sensitivity or intolerance to the study drug, comparator or formulation
ingredients.

14. Participation in any other clinical study within the previous 3 months of screening.

15. Illicit substance abuse within the past 6 months.

16. History or other evidence of severe illness or any other conditions that would make
the patient, in the opinion of the investigator, unsuitable for the study (such as
poorly controlled psychiatric disease, human immunodeficiency virus (HIV), coronary
artery disease or active gastrointestinal conditions that might interfere with drug
absorption).



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Biliary Cirrhosis

Intervention(s)

Drug: Saroglitazar magnesium 2 mg

Drug: Saroglitazar magnesium 4 mg

Drug: Placebo Oral Tablet

Primary Outcome(s)

Effect of a 16-week treatment regimen of Saroglitazar magnesium 2 mg and 4 mg on ALP levels in patients with Primary Biliary Cholangitis. [Time Frame: 16 Weeks]

Secondary ID(s)

SARO.16.004

Source(s) of Monetary Support

Please refer to primary and secondary sponsors