A Phase 1, Open-label Extension Groups Study in Subjects having Hepatic Impairment with Cirrhosis due to Cholestatic Liver Disease
Hepatic impairment study in subjects with cirrhosis secondary to cholestatic disease at a single and multiple once daily doses of Saroglitazar Magnesium needs to be conducted per discussion with FDA. Thus, an extension study has been added.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Group-8: Total of 18 subjects will be enrolled in the Group-8. Group 8A (n=6, consist of mild hepatic impairment subjects); Group 8B (n=6, consist of moderate hepatic impairment), Group 8C (n=3, consist of severe hepatic impairment and Group 8D (n=3, consist of control subjects with normal hepatic functions).
Group-9: Total of 12 subjects will be enrolled in the Group-9. Group 9A (n=3, consist of mild hepatic impairment subjects); Group 9B (n=3, consist of moderate hepatic impairment), Group 9C (n=3, consist of severe hepatic impairment and Group 9D (n=3, consist of control subjects with normal hepatic functions).
Zydus US002
Indianapolis, Indiana, United States
RECRUITINGTo evaluate the plasma PK of Saroglitazar (parent compound)
To measure the plasma concentration of Saroglitazar (parent compound) and estimate the AUCt following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function.
Time frame: Serial PK blood samples will be collected on Day1 and Day 28 (1 pre-dose sample and serial post dose sampling till 24 hours post dose on both days)
To assess the safety and tolerability of Saroglitazar
Percentage of subjects with clinical \& laboratory AEs/SAEs and Treatment emergent AEs/SAEs, coded using the MedDRA following single and once a daily multiple oral doses of 1 mg and 2 mg of Saroglitazar Magnesium in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function
Time frame: Through study completion, an average of 9 weeks
To evaluate plasma PK of Saroglitazar metabolite (Saroglitazar sulfoxide)
To measure the plasma concentration of Saroglitazar metabolite (Saroglitazar sulfoxide) and estimate the AUCt following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function.
Time frame: Serial PK blood samples will be collected on Day 1 and Day 28 (1 pre-dose sample and serial post dose sampling till 24 hours post dose on both days)
To evaluate the impact of hepatic impairment with cirrhosis due to cholestatic liver disease on the unbound concentration of Saroglitazar in systemic circulation in
To measure the differences (between day-01 and Day-28) on unbound concentration of Saroglitazar in systemic circulation following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function
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Time frame: The blood samples will be collected on Day 1 and Day 28 at pre-dose, 2.0 h and 24.0 h post dose.
To evaluate the trough plasma concentration of Saroglitazar (parent compound)
To evaluate the trough plasma concentration of Saroglitazar following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function
Time frame: Trough plasma sample will be collected at pre-dose on Visit 3 (on day 8), Visit-4 (On day 15) and at Visit 5 (on day 22). Additional PK sample will be collected at 168.0 hours post dose of day 28 (i.e. on Day 35 ±3D)
To determine the plasma PK of Saroglitazar (parent compound)
The plasma concentration of Saroglitazar (parent compound) will be measured to estimate the Cmax following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function.
Time frame: Serial PK blood samples will be collected on Day1 and Day 28 (1 pre-dose sample and serial post dose sampling till 24 hours post dose on both days)
To determine the plasma PK of Saroglitazar metabolite (Saroglitazar sulfoxide)
The plasma concentration of Saroglitazar metabolite (Saroglitazar sulfoxide) will be measured to estimate the Cmax following single and once a daily multiple oral doses of 1 mg and 2 mg in subjects with mild, moderate and severe hepatic impairment with cirrhosis due to cholestatic liver disease based on Child-Pugh-Turcotte score compared to subjects with normal hepatic function.
Time frame: Serial PK blood samples will be collected on Day 1 and Day 28 (1 pre-dose sample and serial post dose sampling till 24 hours post dose on both days)