Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00968591
First received: August 27, 2009
Last updated: February 23, 2011
Last verified: February 2011
  Purpose

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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Explore correlation between pharmacokinetics and hepatic function parameters [ Time Frame: First 8 days ] [ Designated as safety issue: No ]

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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00968591

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

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00968591     History of Changes
Other Study ID Numbers: CRAD001X2102, EudraCT 2009-012295-27
Study First Received: August 27, 2009
Last Updated: February 23, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Hepatic insufficiency
liver disease
cirrhosis
pharmacokinetics

Additional relevant MeSH terms:
Hepatic Insufficiency
Digestive System Diseases
Liver Diseases
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014