Clinical trial NCT01565902: Pharmacokinetics of BAF312 in Patients With Hepatic Impairment
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: BAF312
Pharmacokinetics
Hepatic impairment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-03-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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.
* 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.

Primary outcomes:
measure: Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
timeFrame: 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.
measure: 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)
timeFrame: 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.
measure: Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax)
timeFrame: 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:
measure: 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
timeFrame: Day -1 to 22
Other outcomes:
Locations:
city: Balatonfured
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: