Hepatic InsufficiencyPhase 1NCT00968591
Pharmacokinetics of Everolimus in Subjects With Hepatic Insufficiency
A Phase 1 study testing Everolimus in people with Hepatic Insufficiency, run by Novartis Pharmaceuticals at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Insufficiency
- What is being tested?
- Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Nov 2009to Nov 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: An Open-label, Single-dose Study to Assess the Pharmacokinetics of Oral Everolimus (Afinitor®) in Subjects With Impaired Hepatic Function
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
- Being tested
- Everolimus
- Keywords
- Hepatic insufficiency, liver disease, cirrhosis, pharmacokinetics
- Medical subject headings
- Hepatic Insufficiency, Liver Diseases, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
| Study group | Role | What they receive |
|---|---|---|
| RAD001 | Experimental | Not described Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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).
Measured: First 8 days plus day 15 and day 28 post-dose follow-ups for safety
Explore correlation between pharmacokinetics and hepatic function parameters
Measured: First 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2009 (estimated)
- Study startNov 2009
- Primary completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatic InsufficiencyStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00968591
- Sponsor's protocol ID
- CRAD001X2102
- Other IDs
- EudraCT 2009-012295-27
- Status last verified
- Apr 2016
- First submitted
- 27 Aug 2009
- Last updated
- 21 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23453404
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-dose Study to Assess the Pharmacokinetics of Oral Everolimus (Afinitor®) in Subjects With Impaired Hepatic Function
- ClinicalTrials.gov ID
- NCT00968591
- Acronym / sponsor ID
- CRAD001X2102
- Conditions
- Hepatic Insufficiency
- Keywords
- Hepatic insufficiency, liver disease, cirrhosis, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Nov 2010 (actual)
- First posted
- 31 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 | Experimental | Drug: Everolimus |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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).
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus | Drug | RAD001 |
Primary outcome
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
3 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2020.
- Derived from this study: PubMed 23453404Peveling-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 for CRAD001X2102 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Everolimus in people with Hepatic Insufficiency, run by Novartis Pharmaceuticals at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany, Russia, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00968591, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2020.