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Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: August 27, 2009
Last updated: April 20, 2016
Last verified: April 2016
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 Intervention Phase
Hepatic Insufficiency
Drug: Everolimus
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: An Open-label, Single-dose Study to Assess the Pharmacokinetics of Oral Everolimus (Afinitor®) in Subjects With Impaired Hepatic Function

Resource links provided by NLM:

Further study details as provided by Novartis:

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 [ Time Frame: 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. [ Time Frame: 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). [ Time Frame: First 8 days plus day 15 and day 28 post-dose follow-ups for safety ]
  • Explore correlation between pharmacokinetics and hepatic function parameters [ Time Frame: First 8 days ]

Enrollment: 34
Study Start Date: November 2009
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001 Drug: Everolimus


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
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 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

  Contacts and Locations
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Please refer to this study by its identifier: NCT00968591

Novartis Investigative Site
Frankfurt, Germany
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation
Novartis Investigative Site
Singapore, Singapore
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals Identifier: NCT00968591     History of Changes
Other Study ID Numbers: CRAD001X2102
EudraCT 2009-012295-27
Study First Received: August 27, 2009
Last Updated: April 20, 2016

Keywords provided by Novartis:
Hepatic insufficiency
liver disease

Additional relevant MeSH terms:
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents processed this record on May 23, 2017