Clinical trial NCT02491073: Study to Evaluate Serum Free Thyroxine (FT4) and Free Triiodothyronine (FT3) Measurements for Subjects Treated With Eslicarbazeine Acetate (ESL)
Official title: Ex-vivo Study to Evaluate Serum Free Thyroxine (FT4) and Free Triiodothyronine (FT3) Measurements Using Equilibrium Dialysis (ED) and Automated Kit Assay for Subjects Treated With Eslicarbazeine Acetate
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Epilepsy
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-07
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Males and Females greater than or equal to 18 years of age, either exposed to drug or not exposed to drug

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* ESL-exposed Subjects

  1. Subject must give written informed consent and privacy authorization prior to participation in the study.
  2. Male or female patient (≥ 18 years of age) who has received at least 1200 mg QD ESL for at least 6 weeks and has not experienced any rash or other allergic reaction at the time of blood draw.
* Non-ESL-exposed Subjects

  1. Subject must give written informed consent and privacy authorization prior to participation in the study.
  2. Male or female healthy normal volunteer (≥ 18 years of age).

Exclusion Criteria:

* Both ESL-exposed and non-ESL exposed subjects

  1. Subject who does not tolerate venipuncture or Has poor venous access that would cause difficulty for collecting blood samples.
  2. Subject with a history of thyroid disease or clinical condition (eg, renal insufficiency, Sjogren's syndrome, lupus, rheumatoid arthritis, pernicious anemia etc.) that in the opinion of the Investigator may effect levels of thyroid hormones, TBG, and/or TPO antibodies.
  3. Female subject who is pregnant.
  4. Female subject with a positive urine pregnancy test at screening.
  5. Subject who received any excluded medication for at least 30 days prior to blood draw.
  6. Subject has experienced significant blood loss and/or donated blood within last 60 days of blood draw.
  7. Subject intends to donate blood or undergo elective surgery within next 30 days following blood draw.
  8. Subject has donated plasma within last 72 hours of blood draw or intends to donate plasma during study participation.
  9. Subject is, in the opinion of the Investigator, unsuitable in any other way to participate in the study.

Primary outcomes:
measure: Comparison of Concentrations of Free Thyroid Hormones (FT4 and FT3) as Measured by ED and Automated Kit Assay Method in ESL-exposed Subjects
timeFrame: 1 day
measure: 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.
timeFrame: 1 day
Secondary outcomes:
measure: 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.
timeFrame: 1 day
measure: Comparison of Concentrations of Free Thyroid Hormones (FT4 and FT3) in Spiked and Unspiked Volunteer Samples Using ED and Automated Kit Assay.
timeFrame: 1 day
measure: 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.
timeFrame: 1 day
Other outcomes:
Locations:
city: Sun City
country: United States
facility: The More foundation/The Core Institute
state: Arizona
city: Boise
country: United States
facility: Consultans in Epilepsy & Neurology, PLLC
state: Idaho
city: Lexington
country: United States
facility: Bluegrass Epilepsy Research
state: Kentucky
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy Center
state: Maryland
city: Golden Valley
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: New York
country: United States
facility: CliniLabs
state: New York
city: Dallas
country: United States
facility: NeurologicalClinic of Texas, P.A.
state: Texas
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: CNS Medical Director
role: STUDY_CHAIR
References: