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

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.