Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00968591

Collaborator

(none)

Enrollment

Locations

Arm

11.3

Patients Per Site

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Insufficiency	Drug: Everolimus	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RAD001	Drug: Everolimus

Arm

Intervention/Treatment

Experimental: RAD001

Drug: Everolimus

Outcome Measures

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 [First 8 days]

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. [First 8 days]
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]
Explore correlation between pharmacokinetics and hepatic function parameters [First 8 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

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.