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

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).

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Drug: "Basel phenotyping cocktail" capsule

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Ambulantes Studienzentrum, Universitätsspital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: "Basel phenotyping cocktail" capsule; Oral intake of "Basel phenotyping cocktail" capsule and pharmacokinetics (PK) sampling	Drug: "Basel phenotyping cocktail" capsule; Oral intake of "Basel phenotyping cocktail" capsule and pharmacokinetics (PK) sampling

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Stephan Krähenbühl, Universitätsspital Basel, Switzerland

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: CYP450 phenotyping in patients with liver cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 2017-01329

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Results of Trial will be published in a peer reviewed Journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No