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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000562-37 | EudraCT Number |
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This study will investigate the pharmacokinetics of BAF312 in patients with mild, moderate and severe hepatic impairment compared to healthy control subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mild hepatically impaired | Experimental | Treatment with a single oral dose of 0.25 mg BAF312 |
|
| Moderate hepatically impaired | Experimental | Treatment with a single oral dose of 0.25 mg BAF312 |
|
| Severe hepatically impaired | Experimental | Treatment with a single oral dose of 0.25 mg BAF312 |
|
| Matched healthy subjects | Experimental | Treatment with a single oral dose of 0.25 mg BAF312 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BAF312 | Drug | Treatment with a single oral dose of 0.25 mg BAF312 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | The pharmacokinetics of BAF312 were studied in plasma up to 504 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, 312, 408 and 504 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, 312, 408 and 504 hours post dose. |
| Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) | The pharmacokinetics of BAF312 were studied in plasma up to 504 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, 312, 408 and 504 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, 312, 408 and 504 hours post dose. |
| Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) | The pharmacokinetics of BAF312 were studied in plasma up to 504 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, 312, 408 and 504 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, 312, 408 and 504 hours post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Adverse Events, Serious Adverse Events and Death Adverse Events (Frequency of Adverse Events, Serious Adverse Events, and Notable Laboratory Abnormalities) of of BAF312 After a Single Dose of BAF312 | Physical examination, vital signs, body temperature, standard safety laboratory evaluations (hematology, clinical chemistry, coagulation, Hepatitis B and C and HIV serology, α-fetoprotein [in hepatically impaired subjects only], pregnancy test, alcohol and drug screen), standard 12-lead electrocardiogram , cardiac monitoring, 24-h Holter ECG, suicidality assessment (C-SSRS), (serious) adverse event monitoring. |
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Inclusion Criteria:
All subjects:
Hepatic impairment:
- Subjects must have either mild, moderate or severe hepatic impairment
Exclusion Criteria:
All subjects
Hepatic impairment:
Healthy subjects:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Balatonfüred | 8230 | Hungary | |||
| Novartis Investigative Site |
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| Label | URL |
|---|---|
| Publication from the International Journal of Clinical Pharmacology and Therapeutics | View source |
| Results for CBAF312A2122 can be found on the Novartis Clinical Trial Results Website | View source |
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To potentially reduce the number of healthy subjects exposed to BAF312, study allowed for multiple matching of subjects with hepatic impairment to healthy subjects. During the study, 2 healthy subjects were not matched to any of the subjects with hepatic impairment due to a retrospective identification of a better matching partner
Up to forty-eight subjects were planned to be enrolled in four groups. A total of 40 subjects were enrolled and completed the study. All subjects were included in the safety and PK analysis. However, only 38 subjects were included for primary PK analysis based on matched pair analysis
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| ID | Title | Description |
|---|---|---|
| FG000 | Mild Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
| FG001 | Moderate Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
| FG002 | Severe Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
| FG003 | Matched Healthy Subjects | Treatment with a single oral dose of 0.25 mg BAF312 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Mild Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
| BG001 | Moderate Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) | The pharmacokinetics of BAF312 were studied in plasma up to 504 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, 312, 408 and 504 hours post dose. | The PK analysis set consists of all completed subjects with quantifiable pharmacokinetic (PK) measurements. To reduce the number of healthy subjects exposed to BAF312, study allowed matching of subjects with hepatic impairment to healthy subjects. A healthy subject served as matching partner for up to 3 subjects with hepatic impairment | Posted | Mean | Standard Deviation | h*ng/mL | 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, 312, 408 and 504 hours post dose. |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Moderate Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrioventricular block first degree | Cardiac disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
| ID | Term |
|---|---|
| C578989 | siponimod |
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| Day -1 to 22 |
| Budapest |
| 1076 |
| Hungary |
| Novartis Investigative Site | Moscow | 115419 | Russia |
| BG002 | Severe Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
| BG003 | Matched Healthy Subjects | Treatment with a single oral dose of 0.25 mg BAF312 |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Treatment with a single oral dose of 0.25 mg BAF312
| OG001 | Moderate Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
| OG002 | Severe Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 |
| OG003 | Matched Healthy Subjects - Mild | Treatment with a single oral dose of 0.25 mg BAF312 |
| OG004 | Matched Healthy Subjects - Moderate | Treatment with a single oral dose of 0.25 mg BAF312 |
| OG005 | Matched Healthy Subjects - Severe | Treatment with a single oral dose of 0.25 mg BAF312 |
|
|
| Primary | Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) | The pharmacokinetics of BAF312 were studied in plasma up to 504 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, 312, 408 and 504 hours post dose. | The PK analysis set consists of all completed subjects with quantifiable pharmacokinetic (PK) measurements. To reduce the number of healthy subjects exposed to BAF312, study allowed matching of subjects with hepatic impairment to healthy subjects. A healthy subject served as matching partner for up to 3 subjects with hepatic impairment | Posted | Mean | Standard Deviation | h*ng/mL | 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, 312, 408 and 504 hours post dose. |
|
|
|
| Primary | Pharmacokinetic Parameters of BAF312 and Selected Metabolites: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) | The pharmacokinetics of BAF312 were studied in plasma up to 504 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, 312, 408 and 504 hours post dose | The PK analysis set consists of all completed subjects with quantifiable pharmacokinetic (PK) measurements. To reduce the number of healthy subjects exposed to BAF312, study allowed matching of subjects with hepatic impairment to healthy subjects. A healthy subject served as matching partner for up to 3 subjects with hepatic impairment | Posted | Mean | Standard Deviation | (ng/mL) | 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, 312, 408 and 504 hours post dose |
|
|
|
| Secondary | Number of Patients With Adverse Events, Serious Adverse Events and Death Adverse Events (Frequency of Adverse Events, Serious Adverse Events, and Notable Laboratory Abnormalities) of of BAF312 After a Single Dose of BAF312 | Physical examination, vital signs, body temperature, standard safety laboratory evaluations (hematology, clinical chemistry, coagulation, Hepatitis B and C and HIV serology, α-fetoprotein [in hepatically impaired subjects only], pregnancy test, alcohol and drug screen), standard 12-lead electrocardiogram , cardiac monitoring, 24-h Holter ECG, suicidality assessment (C-SSRS), (serious) adverse event monitoring. | The safety analysis set consists of all subjects that received study drug and with no protocol deviations with relevant impact on safety. | Posted | Number | Participants | Day -1 to 22 |
|
|
|
| 0 |
| 8 |
| 1 |
| 8 |
| EG001 | Severe Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 | 0 | 8 | 1 | 8 |
| EG002 | Matched Healthy Subjects | Treatment with a single oral dose of 0.25 mg BAF312 | 0 | 16 | 1 | 16 |
| EG003 | Mild Hepatically Impaired | Treatment with a single oral dose of 0.25 mg BAF312 | 0 | 8 | 0 | 8 |
| Tonsillitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
| Serious Adverse Events |
|
| Death |
|