Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

Hepatic Insufficiency Clinical Trial

Official title:

An Open-label, Single-dose Study to Assess the Pharmacokinetics of Oral Everolimus (Afinitor®) in Subjects With Impaired Hepatic Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00968591
• Other study ID #: CRAD001X2102
• Secondary ID: EudraCT 2009-012
• Status: Completed
• Phase: Phase 1
• Start date: November 2009

Study information

• Verified date: April 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical pharmacology research study will assess the safety and pharmacokinetics of the drug everolimus in patients with impaired hepatic function as compared to healthy volunteers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. primary completion date: November 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

All subjects:

• In good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory test values (except for values related to hepatic insufficiency).

Hepatic impaired subjects:

• A Child-Pugh Classification score clinically determined as Class A, Class B, or Class C.

• Absolute neutrophil count (ANC) > 1000 cells/mm3

• Hemoglobin > 9 mg/mL

• Platelet count > 50,000/mm3 at screening and baseline

• Serum creatinine = 2.0 x ULN

• Free of significant medical disorders unrelated to the subject's hepatic disorder

Exclusion Criteria:

All subjects:

• Significant illness, including infections, or hospitalization within 4 weeks prior to dosing (hospitalization is allowed for hepatic impaired subjects if related to liver disease). Invasive systemic fungal infections need to be fully resolved prior to study entry.

• History of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).

• History of clinically significant drug allergy; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug (everolimus) or drugs similar to the study drug (other mTOR inhibitors, e.g., rapamycin or temsirolimus).

• Active bleeding during the last 28 days prior to dosing, including variceal bleeding.

• Except for hepatic impairment, any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the subject in case of participation in the study.

• Use of tobacco within 7 days prior to dosing or during the study.

• Consumption of alcohol within 3 days prior to dosing or during the study.

• Consumption of grapefruits, grapefruit juice, Sevilla oranges, starfruit or related foods within 7 days prior to dosing or during the study period.

• Use of any drugs known to affect CYP3A4 or PgP, including both inhibitors and inducers, within 7 days prior to dosing or during the study.

Hepatic impaired subjects:

• Symptoms or history of Grade 3 or 4 hepatic encephalopathy within 4 weeks of study entry.

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Hepatic Insufficiency
• Liver Failure

Intervention

Drug:
• Everolimus

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Frankfurt
Russian Federation	Novartis Investigative Site	Moscow
Singapore	Novartis Investigative Site	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  Russian Federation,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the pharmacokinetics of a single oral dose of everolimus in subjects with severely impaired hepatic function (Child-Pugh C) relative to healthy controls. Measure: AUC, Cmax, tmax, ?z, Vd/F, CL/F and t1/2		First 8 days
Secondary	Evaluate the pharmacokinetics of a single oral dose of everolimus in subjects with mild and moderate impaired hepatic function (Child-Pugh A and B, respectively) relative to healthy controls.		First 8 days
Secondary	Assess the safety and tolerability of a single oral dose of everolimus in subjects with impaired hepatic function (Child-Pugh A, B, and C).		First 8 days plus day 15 and day 28 post-dose follow-ups for safety
Secondary	Explore correlation between pharmacokinetics and hepatic function parameters		First 8 days

External Links

•   Results for CRAD001X2102 can be found on the Novartis Clinical Trial Results Website