Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

NCT00968591 | Completed Phase 1

• 2 other identifiers: CRAD001X2102EudraCT 2009-012295-27
• Study Type: interventional
• Target: 34
• Locations: 3 countries
• Sites: 3

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (1)

RAD001

EXPERIMENTAL

Drug: Everolimus

Interventions

Everolimus DRUG

RAD001

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Frankfurt, Germany

Location

Novartis Investigative Site

Moscow, Russia

Location

Novartis Investigative Site

Singapore, Singapore

Location

Related Publications (1)

• 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.

  PMID: 23453404 DERIVED

Related Links

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

MeSH Terms

Conditions

Hepatic Insufficiency; Liver Diseases; Fibrosis

Interventions

Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2009
• First Posted: August 31, 2009
• Study Start: November 1, 2009
• Primary Completion: November 1, 2010
• Last Updated: December 21, 2020

Record last verified: 2016-04

Locations

SG (1); RU (1); DE (1)