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The purpose of this research study is to determine if the blood tests used to measure free thyroid hormone levels are affected by a drug called eslicarbazepine acetate. To determine if eslicarbazepine acetate interferes with these blood tests, blood samples will be analysed so that researchers can compare different types of lab tests that measure these thyroid hormones. Half of the people who participate in this study will already be taking eslicarbazepine acetate either as a study drug or as a prescription (Part 1) and the other half will be people who do not take eslicarbazepine acetate (Part 2).
Part 1 of the study will enroll a minimum of 30 male and female subjects who have received at least 1200 mg once daily (QD) ESL over a minimum 6-week period (ESL-exposed subjects). Subjects, who meet study eligibility requirements and provide written consent, will provide blood samples for measurement of thyroid hormones, thyroxine binding globulins (TBG), serum pregnancy (female subjects of childbearing potential 1only), thyroid peroxidase (TPO) antibodies, and ESL metabolites (eslicarbazepine and (R)-licarbazepine).
Optional blood samples will be requested from subjects in Part 1 who provide genetic consent and are eligible to participate (as controls) in a separate rash registry protocol. These samples will be tested for HLA typing, genetic ancestry, and viral titers (including human herpes virus [HHV]-6, HHV-7, and Epstein-Barr virus [EBV]).
ESL metabolites will be determined by a validated liquid chromatography- tandem mass spectrometry (LC-MS/MS) assay. Levels of FT4 and FT3 in ESL-exposed serum will be assayed using the automated kit assay (Roche Cobas ECLIA kits FT4 II and FT3 III) and Equilibrium Dialysis (ED) method. FT4 and FT3 results measured by both methods will be compared to evaluate potential assay differences. Serum TSH, TT4, TT3, and TBG in ESL treated subject samples will also be measured using automated kit assays.
Part 2 of the study will enroll a minimum of 30 age (± 5 y) and gender-matched non-ESL exposed volunteers. Subjects, who meet study eligibility requirements and provide written consent, will provide a blood sample for measurement of thyroid hormones, TBG, serum pregnancy (female subjects of childbearing potential only), and TPO antibodies. Serum samples obtained from non-ESL exposed subjects will be split into 4 aliquots, one aliquot will be used as the control blank (unspiked) and the rest spiked with 3 levels (high, low, and a concentration representative of therapeutic levels also called middle) of eslicarbazepine (range approximately 5 to 18 μg/mL) and (R)-licarbazepine (range approximately 0.5 to 1.8 μg/mL). The low concentration for spiking the non-ESL exposed samples will be approximately 1 standard deviation (SD) below Cavg associated with the 800 mg dose in chronic use in the epilepsy population and the high concentration for spiking will be approximately 1 SD above Cavg associated with the 1200 mg dose.
After sample is spiked with eslicarbazepine and (R)-licarbazepine, serum FT4 and FT3 will be measured by the automated kit assay method, as well as ED method. FT4 and FT3 measured in non-spiked and spiked volunteer samples will be compared to detect potential in vitro artifacts. Serum TSH, TT4, TT3, and TBG in non-spiked and spiked volunteer samples will also be measured using automated kit assays.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eslicarbazepine acetate treated |
| ||
| Non-Eslicarbazepine acetate treated |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| blood draw | Other | Investigate the possibility of assay artifacts impacting the measurement of thyroid hormones, in particular FT4 and FT3, in ESL treated subjects compared to non-ESL-treated subjects. |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of Concentrations of Free Thyroid Hormones (FT4 and FT3) as Measured by ED and Automated Kit Assay Method in ESL-exposed Subjects | 1 day | |
| Comparison of Concentrations of Free Thyroid Hormones (FT4 and FT3) as Measured by Automated Kit Assay in Non-ESL Exposed Subjects, With and Without the in Vitro Addition of Eslicarbazepine and (R)-Licarbazepine. | 1 day |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of Concentrations of TT4, and TT3 as Measured in Non-ESL-exposed Subject Samples, With or Without the in Vitro Addition of Eslicarbazepine and (R)-Licarbazepine. | 1 day | |
| Comparison of Concentrations of Free Thyroid Hormones (FT4 and FT3) in Spiked and Unspiked Volunteer Samples Using ED and Automated Kit Assay. |
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Inclusion Criteria:
ESL-exposed Subjects
Non-ESL-exposed Subjects
Exclusion Criteria:
Both ESL-exposed and non-ESL exposed subjects
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Males and Females greater than or equal to 18 years of age, either exposed to drug or not exposed to drug
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| Name | Affiliation | Role |
|---|---|---|
| CNS Medical Director | Sumitomo Pharma America, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The More foundation/The Core Institute | Sun City | Arizona | 85351 | United States | ||
| Consultans in Epilepsy & Neurology, PLLC |
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| ID | Title | Description |
|---|---|---|
| FG000 | Eslicarbazepine Acetate Exposed Subjects | Adult male and female subjects (greater than or equal to 18 years)who had received at least 1200 mg QD eslicarbazapine acetate (ESL) for at least 6 weeks and had not experienced any rash or other allergic reaction at the time of the blood draw |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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blood
| 1 day |
| Comparison of Concentrations of TSH,as Measured in Non-ESL-exposed Subject Samples, With or Without the in Vitro Addition of Eslicarbazepine and (R)-Licarbazepine. | 1 day |
| Boise |
| Idaho |
| 83702 |
| United States |
| Bluegrass Epilepsy Research | Lexington | Kentucky | 40504 | United States |
| Mid-Atlantic Epilepsy Center | Bethesda | Maryland | 20817 | United States |
| Minneapolis Clinic of Neurology | Golden Valley | Minnesota | 55422 | United States |
| CliniLabs | New York | New York | 10019 | United States |
| NeurologicalClinic of Texas, P.A. | Dallas | Texas | 75251 | United States |
| Healthy Volunteers |
Adult male and female healthy volunteer (greater than or equal to 18 years) not exposed to ESL at the time of blood draw |
| COMPLETED |
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| NOT COMPLETED |
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the analysis was done on the safety population group
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| ID | Title | Description |
|---|---|---|
| BG000 | Eslicarbazepine Acetate Treated | blood draw: Investigate the possibility of assay artifacts impacting the measurement of thyroid hormones, in particular FT4 and FT3, in ESL treated subjects compared to non-ESL-treated subjects. |
| BG001 | Non-Eslicarbazepine Acetate Treated | blood draw: Investigate the possibility of assay artifacts impacting the measurement of thyroid hormones, in particular FT4 and FT3, in ESL treated subjects compared to non-ESL-treated subjects. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 | Comparison of Concentrations of Free Thyroid Hormones (FT4 and FT3) as Measured by ED and Automated Kit Assay Method in ESL-exposed Subjects | Safety Population: The safety population consisted of all subjects who were enrolled in the study, did not test positive for serum pregnancy (female subjects of childbearing potential only) or TPO antibodies, and provided valid serum samples for evaluating the thyroid hormone assays | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L | 1 day |
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| Primary | Comparison of Concentrations of Free Thyroid Hormones (FT4 and FT3) as Measured by Automated Kit Assay in Non-ESL Exposed Subjects, With and Without the in Vitro Addition of Eslicarbazepine and (R)-Licarbazepine. | Safety Population: The safety population consisted of all subjects who were enrolled in the study, did not test positive for serum pregnancy (female subjects of childbearing potential only) or TPO antibodies, and provided valid serum samples for evaluating the thyroid hormone assays | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L | 1 day |
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| Secondary | Comparison of Concentrations of TT4, and TT3 as Measured in Non-ESL-exposed Subject Samples, With or Without the in Vitro Addition of Eslicarbazepine and (R)-Licarbazepine. | Safety Population: The safety population consisted of all subjects who were enrolled in the study, did not test positive for serum pregnancy (female subjects of childbearing potential only) or TPO antibodies, and provided valid serum samples for evaluating the thyroid hormone assays | Posted | Geometric Mean | Geometric Coefficient of Variation | nmo/L | 1 day |
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| Secondary | Comparison of Concentrations of Free Thyroid Hormones (FT4 and FT3) in Spiked and Unspiked Volunteer Samples Using ED and Automated Kit Assay. | Safety Population: The safety population consisted of all subjects who were enrolled in the study, did not test positive for serum pregnancy (female subjects of childbearing potential only) or TPO antibodies, and provided valid serum samples for evaluating the thyroid hormone assays | Posted | Geometric Mean | Geometric Coefficient of Variation | pmol/L | 1 day |
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| Secondary | Comparison of Concentrations of TSH,as Measured in Non-ESL-exposed Subject Samples, With or Without the in Vitro Addition of Eslicarbazepine and (R)-Licarbazepine. | Safety Population: The safety population consisted of all subjects who were enrolled in the study, did not test positive for serum pregnancy (female subjects of childbearing potential only) or TPO antibodies, and provided valid serum samples for evaluating the thyroid hormone assays | Posted | Geometric Mean | Geometric Coefficient of Variation | mU/L | 1 day |
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One day
Adverse events were collected on the same day as the study visit
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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 | Eslicarbazepine Acetate Exposed Subjects | Adult male and female subjects (greater than or equal to 18 years)who had received at least 1200 mg QD eslicarbazapine acetate (ESL) for at least 6 weeks and had not experienced any rash or other allergic reaction at the time of the blood draw | 0 | 37 | 1 | 37 | ||
| EG001 | Healthy Volunteers | Adult male and female healthy volunteer (greater than or equal to 18 years) not exposed to ESL at the time of blood draw | 0 | 34 | 0 | 34 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA 18.0 | Non-systematic Assessment |
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In the event the study is part of a multi-center study, the first publication of the results of the study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the study at all sites, institution and investigator shall be free to publish
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| CNS Medical Director | Sunovion Pharmaceuticals Inc. | 1-866-503-6351 |
| ID | Term |
|---|---|
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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| >=65 years |
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| 18-39 Years |
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| 40-65 Years |
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| >65 Years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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In each geometric mean ratio estimate, free thyroid hormone levels as measured by the automated kit assay represent the numerator; free thyroid hormone levels as measured by the optimized equilibrium dialysis method represent the denominator.
| There is no hypothesis testing in this study. The sample size was determined outside of statistical considerations; it was required by the U.S. Food and Drug Administration (FDA) in the New Drug Application 022416 Approval Letter issued on 08 November 2013 for PMR 2099-9. | Geometric Mean Ratio | Geometric Mean Ratio | 1.15 | 2-Sided | 90 | 1.09 | 1.22 | parameter dispersion type: Geometric Coefficient of Variation Dispersion Value : FT3: 0.178 | Other | In each geometric mean ratio estimate, free thyroid hormone levels as measured by the automated kit assay represent the numerator; free thyroid hormone levels as measured by the optimized equilibrium dialysis method represent the denominator. |
Free thyroid hormone level in the serum sample of healthy volunteers which was spiked with high level of ESL metabolites |
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thyroid hormone level in the serum sample of healthy volunteers which was spiked with high level of ESL metabolites |
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| OG003 | Optimized Equilibrium Dialysis Method(ED)(LS)Healthyvolunteer | Free thyroid hormone level as measured by the optimized equilibrium dialysis method in the serum sample of healthy volunteers which was spiked with low level of ESL metabolites |
| OG004 | Automated Kit Assay(AK)Med-spikedSerum(MS)Healthy Volunteers | Free thyroid hormone level as measured by the automated kit assay in the serum sample of healthy volunteers which was spiked with medium level of ESL metabolites |
| OG005 | Optimized Equilibrium Dialysis Method(ED)(MS)Healthyvolunteer | Free thyroid hormone level as measured by the optimized equilibrium dialysis method in the serum sample of healthy volunteers which was spiked with medium level of ESL metabolites |
| OG006 | Automated Kit Assay(AK)High-spikedSerum(HS)Healthy Volunteers | Free thyroid hormone level as measured by the automated kit assay in the serum sample of healthy volunteers which was spiked with high level of ESL metabolites |
| OG007 | Optimized Equilibrium Dialysis Method(ED)(HS)Healthyvolunteer | Free thyroid hormone level as measured by the optimized equilibrium dialysis method in the serum sample of healthy volunteers which was spiked with high level of ESL metabolites |
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thyroid hormone level in the serum sample of healthy volunteers which was spiked with high level of ESL metabolites |
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