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

NCT03337945 | Completed DMC

• 1 other identifier: 2017-01329
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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).

Conditions

Liver Cirrhosis

Keywords

CYP450 phenotyping in patients with liver cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

"Basel phenotyping cocktail" capsule

EXPERIMENTAL

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

Drug: "Basel phenotyping cocktail" capsule

Interventions

"Basel phenotyping cocktail" capsule DRUG

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

"Basel phenotyping cocktail" capsule

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

Ambulantes Studienzentrum, Universitätsspital Basel

Basel, 4031, Switzerland

Location

Related Publications (2)

• Duthaler U, Bachmann F, Ozbey AC, Umehara K, Parrott N, Fowler S, Krahenbuhl S. The Activity of Members of the UDP-Glucuronosyltransferase Subfamilies UGT1A and UGT2B is Impaired in Patients with Liver Cirrhosis. Clin Pharmacokinet. 2023 Aug;62(8):1141-1155. doi: 10.1007/s40262-023-01261-3. Epub 2023 Jun 16.

  PMID: 37328712 DERIVED

• 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.

  PMID: 35570253 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stephan Krähenbühl

  Universitätsspital Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 9, 2017
• Study Start: April 4, 2018
• Primary Completion: June 30, 2021
• Study Completion: December 31, 2021
• Last Updated: May 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)