Safety and Effectiveness Study in Patients with Liver and Kidney Related Severe Complications using Ambrisentan (N-003) in Micro Doses

Phase 2

• Conditions: Health Condition 1: K767- Hepatorenal syndrome

• Registration Number: CTRI/2024/01/061915
• Lead Sponsor: oorik Biopharmaceuticals AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 4 March 2024

Recruitment & Eligibility

• Status: ot Yet Recruiting
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

1. Written Informed consent prior to any study-related procedures.2. Age greater than or equal to 18 years and less than or equal to 60 years.3. Male or non-pregnant, non-lactating female. Women of child-bearing potential must have a confirmed negative serum pregnancy test at the time of screening and must use a highly effective contraceptive method throughout the study. Men must use an effective contraception method, and should not donate semen during the study. Men are considered to be fertile from the time of puberty, except for those men with permanent sterility secondary to bilateral orchiectomy. 4. Cirrhosis of the liver by laboratory examination, clinical history or biopsy. 5. History of ascites. 6. Increase in serum creatinine greater than or equal to 0.3 mg/dl (26.5 micro mol/L) from a value obtained in the 7 days prior to admission, OR a serum creatinine greater than or equal to 1.5 mg/dl (132.6 micro mol/L) and is greater than or equal to 1.5-fold above the most recent and lowest value obtained in the last 3 months. 7. Subject has completed 48 hours of diuretic withdrawal and plasma volume expansion with albumin prior to study inclusion (e.g., 1 g/kg for first 24 hours and not to exceed 100 g, followed by 20-40 g in second 24 hours). 8. No sustained improvement in renal function during 48 hours of both diuretic withdrawal and plasma volume expansion with albumin, defined as a decrease in serum creatinine of less than 20% from initial value.

Exclusion Criteria

1. Serum creatinine > 5 mg/dL at the end of the 48-hour diuretic withdrawal and plasma volume expansion with albumin period.

2. Mean arterial pressure (MAP) < 60 mmHg, Large Volume Paracentesis in the 3 days prior to screening.

3. Sepsis, uncontrolled bacterial infection or less than 2 days anti-infective therapy for documented or suspected bacterial infection.

4. Total bilirubin > 8 mg/dL (137 micro mol/L).

5. Serum sodium < 130 mmol/L.

6. International Normalised Ratio (INR) greater than or equal to 3.5.

7. Proteinuria greater than or equal to 500 mg/dL.

8. Microhaematuria > 50 red blood cells per high power field.

9. Clinically significant casts on urinalysis, including granular casts.

10. History or evidence of obstructive uropathy or parenchymal renal disease on ultrasound or other imaging.

11. Subject with a recent history of circulatory shock defined as MAP < 60 mmHg within 5 days prior to screening requiring vasopressors or subjects requires circulatory support with vasopressors during screening.

12. Subject requiring oxygen supplementation or mechanical ventilation.

13. Recent exposure to nephrotoxic agents or exposure to radiographic contrast agents within 72 hrs prior to screening.

14. Superimposed acute liver failure/injury due to factors other than alcohol, including acute viral hepatitis, drugs, medications (e.g., acetaminophen), or other toxins (e.g., mushroom [Amanita] poisoning).

15. Severe cardiovascular disease, including, but not limited to, unstable angina, pulmonary oedema, congestive heart failure (NYHA = II), or persisting symptomatic peripheral vascular disease, myocardial infarction or stable chronic angina within the past 12 months, or any other cardiovascular disease judged by the Investigator to be severe.

16. Subject has a history of Transjugular Intrahepatic Portosystemic shunt (TIPS).

17. Subject with acute variceal bleeding at the time of screening who may undergo pre-emptive TIPS or is anticipated to be treated with terlipressin.

18. Current or recent Renal Replacement Therapy (RRT) within 30 days of enrolment, or anticipation of RRT in the next 3 days after screening.

19. Hepatocellular Carcinoma (HCC) beyond the Milan criteria or other malignancy affecting survival beyond 6 months.

20. Participation in a study of an investigational medical product or device within the last 30 days preceding screening.

21. Hepatic Encephalopathy with West Haven Grade III or IV.

22. Current or recent (30 days prior to enrolment) treatment with endothelin receptor antagonists, including ambrisentan. Subjects receiving midodrine and/or octreotide may be enrolled. Midodrine and octreotide treatment must be stopped prior to enrolment.

23. Estimated life expectancy of less than 3 days. Known allergy or sensitivity to ambrisentan or propylene glycol. History of Idiopathic Pulmonary Fibrosis.

24. Subject is unable or unwilling to follow instructions or comply with study procedures.

Study & Design

• Study Type: Interventional
• Study Design: Not specified