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

Primary Purpose

Liver Cirrhosis

Status

Completed

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

"Basel phenotyping cocktail" capsule

About this trial

This is an interventional diagnostic trial for Liver Cirrhosis focused on measuring CYP450 phenotyping in patients with liver cirrhosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Ambulantes Studienzentrum, Universitätsspital Basel

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

"Basel phenotyping cocktail" capsule

Arm Description

Oral intake of "Basel phenotyping cocktail" capsule and pharmacokinetics (PK) sampling

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT03337945

First Posted

November 6, 2017

Last Updated

May 17, 2022

Sponsor

University Hospital, Basel, Switzerland

1. Study Identification

Unique Protocol Identification Number

NCT03337945

Brief Title

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

Acronym

CombiCapsLC

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Completed

Study Start Date

April 4, 2018 (Actual)

Primary Completion Date

June 30, 2021 (Actual)

Study Completion Date

December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Basel, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Cirrhosis

Keywords

CYP450 phenotyping in patients with liver cirrhosis

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

"Basel phenotyping cocktail" capsule

Arm Type

Experimental

Arm Description

Oral intake of "Basel phenotyping cocktail" capsule and pharmacokinetics (PK) sampling

Intervention Type

Drug

Intervention Name(s)

"Basel phenotyping cocktail" capsule

Intervention Description

Oral intake of "Basel phenotyping cocktail" capsule and pharmacokinetics (PK) sampling

Primary Outcome Measure Information:

Title

Concentration-time profile in plasma

Description

Concentration-time Profiles assessed in Plasma over several time points measuring parent compounds and corresponding metabolites to calculate metabolic ratios

Time Frame

-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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephan Krähenbühl

Organizational Affiliation

Universitätsspital Basel, Switzerland

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ambulantes Studienzentrum, Universitätsspital Basel

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Results of Trial will be published in a peer reviewed Journal

Citations:

PubMed Identifier

35570253

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.

Results Reference

derived

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

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