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Trial registered on ANZCTR


Registration number
ACTRN12613000545763
Ethics application status
Approved
Date submitted
4/05/2013
Date registered
15/05/2013
Date last updated
17/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Open-label study to assess how the pharmacokinetics (i.e. the way the body absorbs, distributes and gets rid of a drug), safety, and tolerability of the drug siponimod are influenced by the presence of specific genetic characteristics (namely CYP2C9 genotypes).
Scientific title
Open-label study to assess the pharmacokinetics, safety and tolerability of siponimod in healthy subjects with CYP2C9 extensive (EM) and poor metabolizer (PM) phenotype.
Secondary ID [1] 282443 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
CBAF312A2128
Linked study record

Health condition
Health condition(s) or problem(s) studied:
The medical condition pursued for siponimod is Secondary Progressive Multiple Sclerosis (SPMS). This study aims to characterize the PK profile of siponimod in healthy subjects with the CYP2C9 extensive and poor metabolizer phenotype.
 289054 0
Condition category
Condition code
Neurological 289394 289394 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is divided in two parts: Part 1 and Part 2. All subjects will complete Part 1 and will be single dosed with Siponimod (BAF312) administered as a 0.25mg oral tablet. After a wash-out period of approximately 6 weeks, only subjects belonging to the poor metabolizer phenotype will roll over to Part 2 when subjects will be dosed in 3 separate consecutive days with Siponimod (BAF312) administered as an oral tablet (Day 1: 0.25 mg; Day 2: 0.25 mg; Day 3: 0.5 mg). Subjects presenting the CYP2C9 *1/*1 genotype are not eligible for Part 2. The genotype group is assessed through a CLIA-validated blood assay in Part 1 of the study, or Part 2 for replacement subjects. To monitor adherence, subjects will be confined to the study site for 3 days during Part 1, and for 5 days during Part 2.
Intervention code [1] 287087 0
Treatment: Drugs
Intervention code [2] 287088 0
Early detection / Screening
Comparator / control treatment
No comparator
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289502 0
Pharmacokinetic parameters from the plasma concentration-time data.
Timepoint [1] 289502 0
From Day 1 to Day 42 for Part 1 (17 samples following pre-specified hourly intervals from Day 1 to Day 3, and 11 samplings, at pre-specified daily intervals from Day 4 to Day 42), and from Day 1 to Day 4 for Part 2 of the study (16 samples in total, of which 13 on Day 3).
Secondary outcome [1] 302627 0
Safety and tolerability assessed through physical examinations, vital signs evaluations, hematology tests, cardiac safety monitoring and completion of a prospective suicidality assessment questionnaire.
Timepoint [1] 302627 0
From Day 1 to Day 42 for Part 1 and from Day 1 to Day 4 for Part 2 of the study.

Eligibility
Key inclusion criteria
1) Healthy male and female subjects aged 18 to 70 years, inclusive.
2) Female subjects must be of non-child bearing potential.
3) Body weight: greater than or equal to 50.0 kg; BMI: 18.0-30.0 kg/m2, inclusive.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Subjects with CYP2C9 *1/*2, *2/*2, and *1/*3 genotypes according to screening results.
2) Clinically significant disease of any major system organ class including (but not limited to) cardiovascular, metabolic, renal, neurological or psychiatric diseases which has not resolved within two weeks prior to initial dosing.
3) History or presence (=screening or first baseline) of any clinically significant ECG abnormalities.
4) Any clinically significant laboratory abnormalities at screening that may jeopardize the subjects' safety throughout the study (as judged by the investigator).
5) Smokers as defined by reported tobacco use or urine cotinine concentrations greater than or equal to 500 ng/mL at screening or baseline visit.
6) Use of any prescription drug, herbal drug or over-the-counter medication from four weeks prior to initial dosing.
7) Pregnant or nursing (lactating) females.
8) Any surgical or medical condition which, as judged by the investigator, might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
The study is divided in two parts (Part 1 and Part 2). All subjects will complete Part 1 and will be single dosed with Siponimod (BAF312). Only specific genotypes will roll over to Part 2 where subjects will be dosed in 3 separate days with Siponimod (BAF312).
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Log-transformed PK parameters for siponimod, will be analyzed by a fixed effects model. The sample size per genotype group is considered to yield satisfactory precision in the estimation of the effect of phenotype, as measured by the ratio of the PK parameter.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/05/2013
Actual
23/05/2013
Date of last participant enrolment
Anticipated
Actual
14/01/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 6820 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 5061 0
France
State/province [1] 5061 0
Country [2] 5062 0
Jordan
State/province [2] 5062 0
Country [3] 5063 0
United States of America
State/province [3] 5063 0

Funding & Sponsors
Funding source category [1] 287222 0
Commercial sector/Industry
Name [1] 287222 0
Novartis Pharma AG
Country [1] 287222 0
Switzerland
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals Australia Pty Limited
Address
54 Waterloo Rd
North Ryde, NSW 2113
Australia
Country
Australia
Secondary sponsor category [1] 285975 0
None
Name [1] 285975 0
Address [1] 285975 0
Country [1] 285975 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294056 0
The Alfred Ethics Committee
Ethics committee address [1] 294056 0
Ethics committee country [1] 294056 0
Australia
Date submitted for ethics approval [1] 294056 0
26/03/2013
Approval date [1] 294056 0
09/04/2013
Ethics approval number [1] 294056 0
96/13

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39786 0
Dr Jason Lickliter
Address 39786 0
Nucleus Network Ltd
Level 5, Burnet Building,
89 Commercial Rd, Melbourne 3004 VIC
Country 39786 0
Australia
Phone 39786 0
+613 9076 8906
Fax 39786 0
Email 39786 0
j.lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 39787 0
Jason Lickliter
Address 39787 0
Nucleus Network Ltd
Level 5, Burnet Building,
89 Commercial Rd, Melbourne 3004 VIC
Country 39787 0
Australia
Phone 39787 0
+613 9076 8906
Fax 39787 0
Email 39787 0
j.lickliter@nucleusnetwork.com.au
Contact person for scientific queries
Name 39788 0
Mike Ufer
Address 39788 0
Novartis Campus
CH-4056 Basel
Switzerland
Country 39788 0
Switzerland
Phone 39788 0
+41 79 7235979
Fax 39788 0
Email 39788 0
mike.ufer@novartis.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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