Pharmacokinetics of BAF312 in Patients With Hepatic Impairment

Phase 1

Completed

Conditions: Hepatic Impairment

Interventions: Drug: BAF312

Registration Number: NCT01565902

Lead Sponsor: Novartis Pharmaceuticals

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mild hepatically impaired	BAF312	Treatment with a single oral dose of 0.25 mg BAF312
Moderate hepatically impaired	BAF312	Treatment with a single oral dose of 0.25 mg BAF312
Severe hepatically impaired	BAF312	Treatment with a single oral dose of 0.25 mg BAF312
Matched healthy subjects	BAF312	Treatment with a single oral dose of 0.25 mg BAF312

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	Day -1 to 22	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.