Hepatic InsufficiencyPhase 1NCT00692341

Evaluation Of Hepatic Impairment On AG-013736 Pharmacokinetics

A Phase 1 study testing AG-013736 in people with Hepatic Insufficiency, run by Pfizer at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study will evaluate the effects of mild and moderate impairment of hepatic function on the single-dose pharmacokinetics, safety and tolerability of AG-013736. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Hepatic Insufficiency
What is being tested?: AG-013736
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 2 sitesUnited States
Study dates: May 2008to Oct 2008
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Diagnosis of reduced hepatic function (Child Pugh Classification A or B)
Body Mass Index of 18-32 kg/m2

Who cannot join

History of febrile illness within 5 days prior to first dose
Any condition possibly affecting drug absorption (e.g. gastrectomy)
Positive urine drug screen

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Pfizer Investigational Site
Miami, Florida, 33169
Pfizer Investigational Site
Orlando, Florida, 32809

Other trials in United States

About this study

Official title: A Phase 1 Study To Evaluate The Pharmacokinetics Of AG-013736 In Subjects With Impaired Hepatic Function

This study will evaluate the effects of mild and moderate impairment of hepatic function on the single-dose pharmacokinetics, safety and tolerability of AG-013736.

Conditions: Hepatic Insufficiency
Being tested: AG-013736
Keywords: hepatic impairment
Medical subject headings: Hepatic Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AG-013736Drug
Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.
AG-013736Drug
Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.
AG-013736Drug
Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.

Study groups in NCT00692341
Study group	Role	What they receive
Hepatic Function - Mild Impairment	Experimental	Subjects with mild hepatic impairment (Child Pugh class A, score 5-6) Receives: Drug: AG-013736
Hepatic Function - Moderate Impairment	Experimental	Subjects with moderate hepatic impairment(Child Pugh class B,score 7-9) Receives: Drug: AG-013736
Hepatic Function - Normal	Experimental	Group 1 1) subjects with normal hepatic function Receives: Drug: AG-013736

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Plasma Concentration (Cmax)
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hours (hrs) post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose

Secondary outcomes (11)

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Plasma Elimination Half-life (t1/2)
Plasma elimination half-life is the time measured for the plasma concentration to decrease by one half.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Apparent Oral Clearance (CL/F)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Apparent Volume of Distribution (Vz/F)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the oral bioavailability.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Fraction of Unbound Drug (fu)
Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Apparent Oral Clearance (CLu/F)
Clearance of an unbound drug is a measure of the rate at which an unbound drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. Unbound drug clearance is a quantitative measure of the rate at which an unbound drug substance is removed from the blood.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Apparent Volume of Distribution (Vzu/F)
Volume of distribution of unbound drug is defined as the theoretical volume in which the total amount of unbound drug would need to be uniformly distributed to produce the desired plasma concentration of unbound drug. Unbound apparent volume of distribution after oral dose (Vzu/F) is influenced by the oral bioavailability.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)u]
AUC (0 - ∞)u = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) for unbound drug. It is obtained from AUCu (0 - t) plus AUCu (t - ∞).
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClastu) for unbound drug.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Maximum Observed Plasma Concentration (Cmaxu)
Cmaxu is the highest measured unbound plasma concentration during the dosing interval.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2008Oct 2008

First posted6 Jun 2008 (estimated)
Study startMay 2008
Primary completionOct 2008
Study completionOct 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hepatic InsufficiencyStudies of the same condition, open and under way.
More trials run by PfizerThe 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: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00692341
Sponsor's protocol ID: A4061036
Status last verified: Apr 2012
First submitted: 4 Jun 2008
Last updated: 11 Apr 2012
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hepatic Insufficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Study To Evaluate The Pharmacokinetics Of AG-013736 In Subjects With Impaired Hepatic Function
ClinicalTrials.gov ID: NCT00692341
Acronym / sponsor ID: A4061036
Conditions: Hepatic Insufficiency
Keywords: hepatic impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: May 2008
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 6 Jun 2008 (estimated)
Results: Posted 27 Mar 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will evaluate the effects of mild and moderate impairment of hepatic function on the single-dose pharmacokinetics, safety and tolerability of AG-013736.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Hepatic Function - Mild Impairment	Experimental	Drug: AG-013736Subjects with mild hepatic impairment (Child Pugh class A, score 5-6)
Hepatic Function - Moderate Impairment	Experimental	Drug: AG-013736Subjects with moderate hepatic impairment(Child Pugh class B,score 7-9)
Hepatic Function - Normal	Experimental	Drug: AG-013736Group 1 1) subjects with normal hepatic function

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Diagnosis of reduced hepatic function (Child Pugh Classification A or B)
Body Mass Index of 18-32 kg/m2

Key exclusion criteria (3 listed)

History of febrile illness within 5 days prior to first dose
Any condition possibly affecting drug absorption (e.g. gastrectomy)
Positive urine drug screen

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
AG-013736Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.	Drug	Hepatic Function - Mild Impairment
AG-013736Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.	Drug	Hepatic Function - Moderate Impairment
AG-013736Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.	Drug	Hepatic Function - Normal

Primary outcome

Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hours (hrs) post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

11 secondary outcomes

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Plasma Elimination Half-life (t1/2)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Apparent Oral Clearance (CL/F)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Apparent Volume of Distribution (Vz/F)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Fraction of Unbound Drug (fu)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Apparent Oral Clearance (CLu/F)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Apparent Volume of Distribution (Vzu/F)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)u]
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Maximum Observed Plasma Concentration (Cmaxu)
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose

Results and safety

Results posted to the registry on 27 Mar 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Axitinib : Normal Hepatic Function	8	8
Axitinib : Mild Hepatic Impairment	8	8
Axitinib : Moderate Hepatic Impairment	8	8

Primary outcome: Maximum Observed Plasma Concentration (Cmax)

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hours (hrs) post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Axitinib : Normal Hepatic Function n = 8	Axitinib : Mild Hepatic Impairment n = 8	Axitinib : Moderate Hepatic Impairment n = 8
Value	30.43 (50.00)	26.96 (127.00)	38.85 (50.00)

Axitinib : Normal Hepatic Function vs Axitinib : Mild Hepatic Impairment: Ratio of adjusted geometric means: 88.61 (90% CI 49.20 to 159.56)
Axitinib : Normal Hepatic Function vs Axitinib : Moderate Hepatic Impairment: Ratio of adjusted geometric means: 127.67 (90% CI 70.90 to 229.91)

Population analysed: Pharmacokinetic (PK) concentration population included all participants who were treated and had at least 1 concentration measurement.

Primary outcome: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Axitinib : Normal Hepatic Function n = 8	Axitinib : Mild Hepatic Impairment n = 8	Axitinib : Moderate Hepatic Impairment n = 8
Value	155.68 (63.00)	121.96 (167.00)	303.96 (44.00)

Axitinib : Normal Hepatic Function vs Axitinib : Mild Hepatic Impairment: Ratio of adjusted geometric means: 78.34 (90% CI 39.92 to 153.75)
Axitinib : Normal Hepatic Function vs Axitinib : Moderate Hepatic Impairment: Ratio of adjusted geometric means: 195.25 (90% CI 99.49 to 383.18)

Population analysed: PK parameter analysis population included all participants who were treated and had at least 1 of the PK parameters of interest.

11 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Axitinib : Normal Hepatic Function	0 of 8 (0%)	3 of 8 (37.5%)	Not reported
Axitinib : Mild Hepatic Impairment	0 of 8 (0%)	0 of 8 (0%)	Not reported
Axitinib : Moderate Hepatic Impairment	0 of 8 (0%)	0 of 8 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Hepatic Insufficiency

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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.

Pfizer CT.gov Call Center study director

Pfizer

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AG-013736 in people with Hepatic Insufficiency, run by Pfizer at 2 sites in United States.

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 2 inclusion and 3 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 11 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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?

Yes. Results are posted in the registry (first posted 27 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Observed Plasma Concentration (Cmax) (time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hours (hrs) post-dose). The study lists 2 primary outcomes in all. 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 NCT00692341.

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 11 Apr 2012.