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

NCT01904214 | Completed Phase 1

• 1 other identifier: CBAF312A2129
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 2

Brief 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

Conditions

Renal Impairment

Keywords

renal impairement; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of participants with Adverse Events as a measure of Safety and Tolerability

  Day 1 - Day 14

Study Arms (4)

severe renal impairmnt

EXPERIMENTAL

Drug: BAF312

moderate renal impairment

EXPERIMENTAL

Drug: BAF312

mild renal impairment

EXPERIMENTAL

Drug: BAF312

healthy subjects

EXPERIMENTAL

Drug: BAF312

Interventions

BAF312 DRUG

Treatment with a single oral dose of 0.25 mg BAF312

healthy subjects; mild renal impairment; moderate renal impairment; severe renal impairmnt

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Orlando, Florida, 32809, United States

Location

Novartis Investigative Site

Bucharest, Romania

Location

Related Links

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

MeSH Terms

Conditions

Renal Insufficiency

Interventions

siponimod

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2013
• First Posted: July 22, 2013
• Study Start: July 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: December 8, 2020

Record last verified: 2018-02

Locations

US (1); RO (1)