Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

NCT ID: NCT00968591

Last Updated: 2020-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30

Brief 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.

Conditions

Hepatic Insufficiency

Keywords

Hepatic insufficiency; liver disease; cirrhosis; pharmacokinetics

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

RAD001

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Interventions

Everolimus

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Frankfurt, , Germany

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Singapore, , Singapore

Countries

Germany; Russia; Singapore

References

Peveling-Oberhag J, Zeuzem S, Yong WP, Kunz T, Paquet T, Bouillaud E, Urva S, Anak O, Sellami D, Kobalava Z. Effects of hepatic impairment on the pharmacokinetics of everolimus: a single-dose, open-label, parallel-group study. Clin Ther. 2013 Mar;35(3):215-25. doi: 10.1016/j.clinthera.2013.02.007. Epub 2013 Mar 1.

Reference Type: DERIVED

PMID: 23453404 (View on PubMed)

Related Links

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=4242

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

Other Identifiers

EudraCT 2009-012295-27

Identifier Type: -

Identifier Source: secondary_id

CRAD001X2102

Identifier Type: -

Identifier Source: org_study_id