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Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

Primary Purpose

Hepatic Insufficiency

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Everolimus

About this trial

This is an interventional other trial for Hepatic Insufficiency focused on measuring Hepatic insufficiency, liver disease, cirrhosis, pharmacokinetics

Eligibility Criteria

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

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

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001

Arm Description

Outcomes

Primary Outcome Measures

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, λz, Vd/F, CL/F and t1/2

Secondary Outcome Measures

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.

Assess the safety and tolerability of a single oral dose of everolimus in subjects with impaired hepatic function (Child-Pugh A, B, and C).

Explore correlation between pharmacokinetics and hepatic function parameters

Full Information

NCT ID

NCT00968591

First Posted

August 27, 2009

Last Updated

December 17, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00968591

Brief Title

Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

November 2010 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

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

Hepatic Insufficiency

Keywords

Hepatic insufficiency, liver disease, cirrhosis, pharmacokinetics

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RAD001

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Everolimus

Primary Outcome Measure Information:

Title

Time Frame

First 8 days

Secondary Outcome Measure Information:

Title

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.

Time Frame

First 8 days

Title

Assess the safety and tolerability of a single oral dose of everolimus in subjects with impaired hepatic function (Child-Pugh A, B, and C).

Time Frame

First 8 days plus day 15 and day 28 post-dose follow-ups for safety

Title

Explore correlation between pharmacokinetics and hepatic function parameters

Time Frame

First 8 days

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: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Frankfurt

Country

Germany

Facility Name

Novartis Investigative Site

City

Moscow

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Singapore

Country

Singapore

12. IPD Sharing Statement

Citations:

PubMed Identifier

23453404

Citation

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.

Results Reference

derived

Links:

URL

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

Description

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

Learn more about this trial

Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

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