Clinical trial NCT03337945: In Vivo Determination of Cytochrome P450 Activities in Patients With Liver Cirrhosis
Official title: In Vivo Determination of Cytochrome P450 Activities in Patients With Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Cirrhosis
Keywords: CYP450 phenotyping in patients with liver cirrhosis
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2017-11-09
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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
Primary purpose: DIAGNOSTIC

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Concentration-time profile in plasma
timeFrame: -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
Secondary outcomes:
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Ambulantes Studienzentrum, Universitätsspital Basel
Study officials:
affiliation: Universitätsspital Basel, Switzerland
name: Stephan Krähenbühl
role: PRINCIPAL_INVESTIGATOR
References:
citation: Duthaler U, Bachmann F, Suenderhauf C, Grandinetti T, Pfefferkorn F, Haschke M, Hruz P, Bouitbir J, Krahenbuhl S. Liver Cirrhosis Affects the Pharmacokinetics of the Six Substrates of the Basel Phenotyping Cocktail Differently. Clin Pharmacokinet. 2022 Jul;61(7):1039-1055. doi: 10.1007/s40262-022-01119-0. Epub 2022 May 16.