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

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

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: BAF312

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Romania
  • Bucuresti, Romania
    • Novartis Investigative Site
• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mild renal impairment	Drug: BAF312; Treatment with a single oral dose of 0.25 mg BAF312
Experimental: healthy subjects	Drug: BAF312; Treatment with a single oral dose of 0.25 mg BAF312
Experimental: severe renal impairmnt	Drug: BAF312; Treatment with a single oral dose of 0.25 mg BAF312
Experimental: moderate renal impairment	Drug: BAF312; Treatment with a single oral dose of 0.25 mg BAF312

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: July 17, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimate): July 22, 2013

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: pharmacokinetics; renal impairement
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Siponimod
• Other Study ID Numbers: CBAF312A2129