Pharmacokinetics of BAF312 in Patients With Hepatic Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01565902
First received: March 26, 2012
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Hepatic Impairment
Drug: BAF312
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
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.

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Pharmacokinetic parameters of BAF312 and selected metabolites [ 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. ] [ Designated as safety issue: No ]
    The pharmacokineticsof BAF312 will be 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. Selected metabolites will also be quantified using the same samples as described above. Free plasma circulating fraction of BAF312 will also be investigated to assess whether protein binding is affected by hepatic impairment. For this purpose a separate blood sample will be taken at the following time point: 4 hours post-dose.


Secondary Outcome Measures:
  • To investigate the safety and tolerability of BAF312 after a single dose of BAF312 in [ Time Frame: Day -1 to 22 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 35
Study Start Date: October 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1-mild
Treatment with a single oral dose of 0.25 mg BAF312
Drug: BAF312
Treatment with a single oral dose of 0.25 mg BAF312
Experimental: 2-moderate
Treatment with a single oral dose of 0.25 mg BAF312
Drug: BAF312
Treatment with a single oral dose of 0.25 mg BAF312
Experimental: 3-severe
Treatment with a single oral dose of 0.25 mg BAF312
Drug: BAF312
Treatment with a single oral dose of 0.25 mg BAF312
Experimental: 4-HV
Treatment with a single oral dose of 0.25 mg BAF312
Drug: BAF312
Treatment with a single oral dose of 0.25 mg BAF312

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565902

Locations
Hungary
Novartis Investigative Site
Balatonfured, Hungary, 8230
Novartis Investigative Site
Budapest, Hungary, 1076
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 115419
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01565902     History of Changes
Other Study ID Numbers: CBAF312A2122, 2012-000562-37
Study First Received: March 26, 2012
Last Updated: June 13, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy

Keywords provided by Novartis:
BAF312
Pharmacokinetics
Hepatic impairment

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 28, 2014