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
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
| 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
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic parameters of BAF312 and selected metabolites [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]
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.
Secondary Outcome Measures
- Number of participants with Adverse Events as a measure of Safety and Tolerability [Day 1 - Day 14]
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.
Eligibility Criteria
Criteria
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
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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.
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Orlando | Florida | United States | 32809 |
| 2 | Novartis Investigative Site | Bucuresti | Romania |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Results for CBAF312A2129 can be found on the Novartis Clinical Trial Results website
- Pubmed publication
Publications
None provided.- CBAF312A2129