A Single-dose, Open-label, Parallel-group Study to Assess the Pharmacokinetics of BAF312 in Subjects With Renal Impairment Compared to Subjects With Normal Renal Function

Renal Impairment Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01904214
• Other study ID #: CBAF312A2129
• Status: Completed
• Phase: Phase 1
• Start date: July 2013
• Est. completion date: November 2014

Study information

• Verified date: February 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

to quantify the effect of different degrees of renal impairment on the pharmacokinetics of BAF312 (and selected metabolites) and to assess safety and tolerability in order to develop dosing recommendations for subjects with renal impairment

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

All subjects:

• At least 50 kg and body mass index (BMI) within 18-38 kg/m2.
• CYP2C9 wild-type (CYP2C9*1 homozygous carriers)

Renal impairment:

• Subjects must have either mild, moderate or severe renal impairment Exclusion Criteria: All subjects
• 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.
• Women of child-bearing potential
• History of malignancy of any organ system
• 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.

Renal 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 renal 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. Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• BAF312
Treatment with a single oral dose of 0.25 mg BAF312

Locations

Country	Name	City	State
Romania	Novartis Investigative Site	Bucuresti
United States	Novartis Investigative Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameters of BAF312 and selected metabolites	The pharmacokineticsof BAF312 will be studied in plasma up to 312 (+/-24) 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, and 312 (+/-24) 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 renal impairment. For this purpose a separate blood sample will be taken at the following time point: 4 hours post-dose.	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, and 312 hours post dose
Secondary	Number of participants with Adverse Events as a measure of Safety and Tolerability	Physical examination, vital signs, body temperature, standard safety laboratory evaluations (hematology, clinical chemistry, coagulation, Hepatitis B and C and HIV serology, pregnancy test, alcohol and drug screen), standard 12-lead electrocardiogram , cardiac monitoring, 24-h Holter ECG, (serious) adverse event monitoring.	Day 1 - Day 14

External Links

•   Pubmed publication
•   Results for CBAF312A2129 can be found on the Novartis Clinical Trial Results website