Hepatic ImpairmentPhase 1NCT01565902

Pharmacokinetics of BAF312 in Patients With Hepatic Impairment

A Phase 1 study testing BAF312 in people with Hepatic Impairment, run by Novartis Pharmaceuticals at 3 sites in 2 countries.

Completed

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

Official record

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Trial summary

This study will investigate the pharmacokinetics of BAF312 in patients with mild, moderate and severe hepatic impairment compared to healthy control subjects. Read more about this study

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Hepatic Impairment
What is being tested?: BAF312
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 3 sitesin 2 countries
Study dates: Oct 2012to Mar 2014
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 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

All subjects:
Male and female Caucasian subjects 18 to 70 years of age
At least 50 kg and body mass index (BMI) within 18-35 kg/m2.
CYP2C9 wild-type (CYP2C9*1 homozygous carriers)
Hepatic impairment:
Subjects must have either mild, moderate or severe hepatic impairment

Who cannot join

All subjects
Hepatic impairment due to non-liver disease.
Use of other investigational drugs within certain timelines
Donation or loss of 400 mL or more of blood or plasma within eight (8) weeks prior to initial dosing
History of cardiac rhythm abnormalities or cardiac rhythm abnormalities identified in the 24-h Holter ECG recording including episodes of bradycardia (HR < 50 bpm) during waking hours and/or arrhythmic episodes; subjects with history or presence of ventricular rhythm disturbances (ventricular extra-systoles >100/24h, or higher grade), or supraventricular arrhythmias (other than occasional supraventricular ectopic beats with a maximum of 5 subsequent ectopic beats per event) or subjects with conduction disturbances (higher than AV-block grade 1) or bradycardia or tachycardia.
History of cardiac catheter ablation.

Show all 21Show fewer

Women of child-bearing potential
History of malignancy of any organ system
Recent and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease)
History or presence of symptomatic postural hypotension or syncope.
Total WBC or lymphocyte counts which falls outside the 1.5-fold local laboratory normal range or platelet count < 30,000/μL at screening or baseline.
Clinically significant infection or recent vaccination with live-attenuated vaccines.
History or presence of hepatitis B or C and/or positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at screening.
History or presence of coronary heart disease (stable or unstable), myocardial infarction, myocarditis, cardiomyopathy, heart failure NYHA II - IV.
Hepatic impairment:
History or presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk.
Any surgical or medical condition other than hepatic impairment which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the safety of the study subject in case of participation in the study.
Treatment with certain drugs
Healthy subjects:
History or presence of any clinically significant disease of any major system organ class including (but not limited to) cardiovascular, metabolic, renal, neurological or psychiatric diseases.
Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, drugs, or which may jeopardize the subject in case of participation in the study.

Trial locations and contacts

3 sites in 2 countries.

Country

City, postcode or hospital

3 sites in 2 countries

Hungary2 sites

Novartis Investigative Site
Balatonfüred, 8230
Novartis Investigative Site
Budapest, 1076

Other trials in Hungary

Russia1 site

Novartis Investigative Site
Moscow, 115419

Other trials in Russia

About this study

Official title: A Single-dose, Open-label, Parallel-group Study to Assess the Pharmacokinetics of BAF312 in Subjects With Mild, Moderate and Severe Hepatic Impairment Compared to Healthy Control Subjects.

This study will investigate the pharmacokinetics of BAF312 in patients with mild, moderate and severe hepatic impairment compared to healthy control subjects.

Conditions: Hepatic Impairment
Being tested: BAF312
Keywords: BAF312, Pharmacokinetics, Hepatic impairment

What participants receive

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

BAF312Drug
Treatment with a single oral dose of 0.25 mg BAF312

Study groups in NCT01565902
Study group	Role	What they receive
Mild hepatically impaired	Experimental	Treatment with a single oral dose of 0.25 mg BAF312 Receives: Drug: BAF312
Moderate hepatically impaired	Experimental	Treatment with a single oral dose of 0.25 mg BAF312 Receives: Drug: BAF312
Severe hepatically impaired	Experimental	Treatment with a single oral dose of 0.25 mg BAF312 Receives: Drug: BAF312
Matched healthy subjects	Experimental	Treatment with a single oral dose of 0.25 mg BAF312 Receives: Drug: BAF312

What is being measured

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

Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
Measured: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
Measured: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax)
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose
Measured: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose

Secondary outcomes (1)

Number of Patients With Adverse Events, Serious Adverse Events and Death Adverse Events (Frequency of Adverse Events, Serious Adverse Events, and Notable Laboratory Abnormalities) of of BAF312 After a Single Dose of BAF312
Physical examination, vital signs, body temperature, standard safety laboratory evaluations (hematology, clinical chemistry, coagulation, Hepatitis B and C and HIV serology, α-fetoprotein [in hepatically impaired subjects only], pregnancy test, alcohol and drug screen), standard 12-lead electrocardiogram , cardiac monitoring, 24-h Holter ECG, suicidality assessment (C-SSRS), (serious) adverse event monitoring.
Measured: Day -1 to 22

Timeline

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

Oct 2012Mar 2014

First posted29 Mar 2012 (estimated)
Study startOct 2012
Primary completionMar 2014
Study completionMar 2014

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 ImpairmentStudies 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01565902
Sponsor's protocol ID: CBAF312A2122
Other IDs: 2012-000562-37
Status last verified: Feb 2018
First submitted: 26 Mar 2012
Last updated: 29 Dec 2020
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 Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single-dose, Open-label, Parallel-group Study to Assess the Pharmacokinetics of BAF312 in Subjects With Mild, Moderate and Severe Hepatic Impairment Compared to Healthy Control Subjects.
ClinicalTrials.gov ID: NCT01565902
Acronym / sponsor ID: CBAF312A2122
Conditions: Hepatic Impairment
Keywords: BAF312, Pharmacokinetics, Hepatic impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Oct 2012
Primary completion: Mar 2014 (actual)
Study completion: Mar 2014 (actual)
First posted: 29 Mar 2012 (estimated)
Results: Posted 22 Dec 2014

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 investigate the pharmacokinetics of BAF312 in patients with mild, moderate and severe hepatic impairment compared to healthy control subjects.

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Mild hepatically impaired	Experimental	Drug: BAF312Treatment with a single oral dose of 0.25 mg BAF312
Moderate hepatically impaired	Experimental	Drug: BAF312Treatment with a single oral dose of 0.25 mg BAF312
Severe hepatically impaired	Experimental	Drug: BAF312Treatment with a single oral dose of 0.25 mg BAF312
Matched healthy subjects	Experimental	Drug: BAF312Treatment with a single oral dose of 0.25 mg BAF312

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Male and female Caucasian subjects 18 to 70 years of age
At least 50 kg and body mass index (BMI) within 18-35 kg/m2.
CYP2C9 wild-type (CYP2C9*1 homozygous carriers)
Subjects must have either mild, moderate or severe hepatic impairment

Key exclusion criteria (21 listed)

All subjects
Hepatic impairment due to non-liver disease.
Use of other investigational drugs within certain timelines
Donation or loss of 400 mL or more of blood or plasma within eight (8) weeks prior to initial dosing
History of cardiac rhythm abnormalities or cardiac rhythm abnormalities identified in the 24-h Holter ECG recording including episodes of bradycardia (HR < 50 bpm) during waking hours and/or arrhythmic episodes; subjects with history or presence of ventricular rhythm disturbances (ventricular extra-systoles >100/24h, or higher grade), or supraventricular arrhythmias (other than occasional supraventricular ectopic beats with a maximum of 5 subsequent ectopic beats per event) or subjects with conduction disturbances (higher than AV-block grade 1) or bradycardia or tachycardia.

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
BAF312Treatment with a single oral dose of 0.25 mg BAF312	Drug	Matched healthy subjects, Mild hepatically impaired, Moderate hepatically impaired, Severe hepatically impaired

Primary outcome

Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
Time frame: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
Time frame: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax)
Time frame: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose

1 secondary outcome

Number of Patients With Adverse Events, Serious Adverse Events and Death Adverse Events (Frequency of Adverse Events, Serious Adverse Events, and Notable Laboratory Abnormalities) of of BAF312 After a Single Dose of BAF312
Time frame: Day -1 to 22

Results and safety

Results posted to the registry on 22 Dec 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mild Hepatically Impaired	8	8
Moderate Hepatically Impaired	8	8
Severe Hepatically Impaired	8	8
Matched Healthy Subjects	16	16

Primary outcome: Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)

Time frame: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.. Mean (Standard Deviation). Unit: h*ng/mL

Measure	Mild Hepatically Impaired n = 8	Moderate Hepatically Impaired n = 7	Severe Hepatically Impaired n = 8	Matched Healthy Subjects - Mild n = 8	Matched Healthy Subjects - Moderate n = 8	Matched Healthy Subjects - Severe n = 8
Value	68.3 (24.5)	53.9 (7.57)	73.7 (25.4)	64.2 (20.8)	63.2 (18.6)	64.9 (23.6)

Population analysed: The PK analysis set consists of all completed subjects with quantifiable pharmacokinetic (PK) measurements. To reduce the number of healthy subjects exposed to BAF312, study allowed matching of subjects with hepatic impairment to healthy subjects. A healthy subject served as matching partner for up to 3 subjects with hepatic impairment

Primary outcome: Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)

Time frame: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.. Mean (Standard Deviation). Unit: h*ng/mL

Measure	Mild Hepatically Impaired n = 8	Moderate Hepatically Impaired n = 7	Severe Hepatically Impaired n = 8	Matched Healthy Subjects - Mild n = 8	Matched Healthy Subjects - Moderate n = 8	Matched Healthy Subjects - Severe n = 8
Value	66.8 (24.4)	52.3 (7.51)	71.6 (24.5)	62.5 (20.9)	61.7 (18.7)	63.4 (23.6)

Primary outcome: Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax)

Time frame: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose. Mean (Standard Deviation). Unit: (ng/mL)

Measure	Mild Hepatically Impaired n = 8	Moderate Hepatically Impaired n = 7	Severe Hepatically Impaired n = 8	Matched Healthy Subjects - Mild n = 8	Matched Healthy Subjects - Moderate n = 8	Matched Healthy Subjects - Severe n = 8
Value	2.03 (0.532)	1.54 (0.191)	1.58 (0.304)	1.74 (0.439)	1.80 (0.417)	1.94 (0.603)

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Moderate Hepatically Impaired	0 of 8 (0%)	1 of 8 (12.5%)	Not reported
Severe Hepatically Impaired	0 of 8 (0%)	1 of 8 (12.5%)	Not reported
Matched Healthy Subjects	0 of 16 (0%)	1 of 16 (6.3%)	Not reported
Mild Hepatically Impaired	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 29 Dec 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Publication from the International Journal of Clinical Pharmacology and TherapeuticsLink provided by the sponsor.
Results for CBAF312A2122 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.

Related trials for Hepatic Impairment

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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 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BAF312 in people with Hepatic Impairment, run by Novartis Pharmaceuticals at 3 sites in 2 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 6 inclusion and 21 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 29 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 Hungary, Russia. 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 22 Dec 2014). 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?

Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) (time frame: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.). The study lists 3 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 NCT01565902.

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 29 Dec 2020.