In Vivo Determination of Cytochrome P450 Activities in Patients With Liver Cirrhosis

Study Overview
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Brief Summary
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Subjects will receive the Basel phenotyping cocktail capsule orally with 120-200ml tap water in fasted state. After intake peripheral venous blood samples will be drawn. 12 patients (male and female) with liver cirrhosis for each Child Pugh Category A, B, and C, and 12 age- and gender-matched healthy control subjects will be included (in total 48 participants).

Official Title
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In Vivo Determination of Cytochrome P450 Activities in Patients With Liver Cirrhosis

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: Basel phenotyping cocktail capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Full mental and legal capacity. Signed informed consent prior to any study related procedure. Ability to communicate in German, sufficient to comprehend and adhere to study protocol. Normal physical examination, vital signs, laboratory workup, and CombiCaps LC Study Protocol Version 1.2 09.08.2017 Page 9 of 50 electrocardiogram (ECG) (in the opinion of investigator). Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening (in the opinion of investigator). No other conditions or circumstances that might interfere with compliance with study protocol (in the opinion of investigator). Exclusion Criteria: Known hypersensitivity to probe substances or any excipient of the drug formulation. Ongoing or past treatment with another investigational drug within 30 days prior to screening. Concomitant treatment with drugs that inhibit or induce CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2B6 and CYP1A2 function (in the opinion of investigator). Actual infection Severe heart failure (NYHA IV). Actual alcohol or drug abuse Positive results from urine drug screen at screening. Excessive caffeine consumption, defined as >800 mg per day at screening*. Subjects unwilling to stop consumption of alcoholic- and caffeine-containing beverages on study days until after the last sampling time-point of the study period. Intake of food products (immediately before or during study) known to be inducers or inhibitors of CYP450 (e.g. grapefruit juice) Loss of 250 ml or more of blood within 3 months prior to screening. Pregnant or lactating women Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. Legal incapacity or limited legal capacity at screening. *100 mg caffeine is approximately 1'000 ml Coca Cola®, 2½ espresso cups or 1 cup of strong coffee.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: A single center, single dose, open label, single period study to characterize cytochrome P450 (CYP) isoforms by the use of the Basel Phenotyping cocktail in patients at different stages of liver cirrhosis
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Basel phenotyping cocktail capsule<br>Oral intake of Basel phenotyping cocktail capsule and pharmacokinetics (PK) sampling | Drug: Basel phenotyping cocktail capsule<br>* Oral intake of Basel phenotyping cocktail capsule and pharmacokinetics (PK) sampling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration-time profile in plasma | Concentration-time Profiles assessed in Plasma over several time points measuring parent compounds and corresponding metabolites to calculate metabolic ratios | -5 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CYP450 phenotyping in patients with liver cirrhosis