A Study To Compare The Effects Of The Infusion Of A Sepsis Drug Between Healthy Adults And Adults With Damaged Livers

Study Overview
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Brief Summary
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This compound, GR270773, is a lipid based compound being developed to treat Sepsis. Lipids are broken down in the body by the liver. This study is designed to see whether the effect of the drug in people with poorly functioning livers is any different to the effect on healthy adults.

Official Title
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An Open-Label, Non-Randomised, Pharmacokinetic, Metabolic Disposition and Safety Study of a 3 Day Continuous Infusion of GR270773 in Healthy Subjects and Subjects With Hepatic Impairment.

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Intravenous GR270773 - Phospholipid emulsion


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with known history of liver disease (either with or without history of alcohol abuse). Previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique. Child-Pugh score of 7-9 (moderate impairment) BMI 19-29 Kg/m2. Healthy volunteers to match the hepatically impaired subjects in a 1:1 ratio by gender, age, BMI. Exclusion criteria: Lactating or pregnant females. Subjects with BP > 160/90. Subjects who, within the past six months, have had a history of significant drug or alcohol abuse, or any indication of regular use of more than 14 units of alcohol per week for women, or 21 units/week for men.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with moderate hepatic impairment<br>Subjects with moderate hepatic impairment as defined by a Child-Pugh score of 7-9 will be included. Subjects will be given GR270773 as a loading infusion of 25 milligram per kilogram per hour (mg/kg/hr) for 2 hours followed by a maintenance infusion of 5 mg/kg/hr for 70 hours. | Drug: Intravenous GR270773 - Phospholipid emulsion<br>* GR270773 (lipid emulsion) is a sterile, white to off-white, semi-translucent liquid for intravenous injection.<br>|
| Experimental: Healthy subjects<br>Subjects will be matched as closely as possible to the group of moderate hepatic subjects for gender, age and body mass index (BMI). Subjects will be administered 25 mg/kg/hr GR270773 as a loading dose for 2 hours followed by a maintenance infusion of 5 mg/kg/hr for 70 hours. Following a washout period of 21 days, the subjects will then receive a loading dose of 75 mg/kg/hr for 2 hours followed by a maintenance dose of 12.5 mg/kg/hr of GR270773 for 70 hours. | Drug: Intravenous GR270773 - Phospholipid emulsion<br>* GR270773 (lipid emulsion) is a sterile, white to off-white, semi-translucent liquid for intravenous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare drug concentrations in the blood between patients with impaired liver function and normal healthy adults, after 72 hours. Determine whether administration of study drug alters the lipid make-up of healthy adults in any way. |  | Up to Day 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine drug concentrations in blood after 2 hour run-in period and after 72 hour infusion period. Determine whether administration of study drug alters the lipid make-up of patients with impaired liver function in any way. |  | Up to Day 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Impairment, GR270773, Emulsion