Pharmacokinetics of BAF312 in Patients With Hepatic Impairment

Novartis

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: BAF312

Study type: Interventional

Funder types: Industry

Identifiers

NCT01565902

2012-000562-37 (EudraCT Number)

CBAF312A2122

Details and patient eligibility

About

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

Enrollment: 40 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 4 patient groups

Mild hepatically impaired

Experimental group

Description:

Treatment with a single oral dose of 0.25 mg BAF312

Treatment:

Drug: BAF312

Moderate hepatically impaired

Experimental group

Description:

Treatment with a single oral dose of 0.25 mg BAF312

Treatment:

Drug: BAF312

Severe hepatically impaired

Experimental group

Description:

Treatment with a single oral dose of 0.25 mg BAF312

Treatment:

Drug: BAF312

Matched healthy subjects

Experimental group

Description:

Treatment with a single oral dose of 0.25 mg BAF312

Treatment:

Drug: BAF312