The study is comprised of two cohorts. Cohort 1 will examine pharmacokinetics of K9 in 3 healthy volunteers over 24 hours. This cohort has been completed. Cohort 2 will involve up to 10 patients with TED. Patients will receive oral K9 BID for up to 24 weeks and will be followed up to a total of 26 weeks with a primary endpoint of safety.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
4
96 mg tablets taken twice a day for 24 weeks
96 mg tablets taken once
University of Kentucky
Lexington, Kentucky, United States
Adverse Events
Frequency of participants experiencing ocular or systemic adverse events.
Time frame: 26 weeks
plasma concentrations of K9
plasma concentrations measured after a single oral dose in healthy adults. For each of these time points 5 ml of blood will be drawn.
Time frame: Pharmacokinetic samples collected pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after dosing
Change in Standardized Patient Evaluation of Eye Dryness (SPEED) symptoms
The SPEED Questionnaire will be used to track progression of dry eye symptoms. The SPEED questionnaire has eight questions. The frequency and severity of symptoms are rated on a numeric scale. Scores range from 0 to 28 with higher scores equating to more symptoms.
Time frame: Screening (Baseline), and Weeks 4, 14, and 24
Change in Diplopia
Diplopia is assessed by the Bahn-Gorman Scale. The Bahn-Gorman scale is a subjective grading scheme that uses a scale of 0-3 to assess the severity of diplopia. A higher score equates to more severe diplopia.
Time frame: Screening (Baseline), Day 1 Visit, and weeks 4, 14, and 24
Change in Study Visit in Clinical Activity Score (CAS),
Clinical Activity Score (7 point scale) with higher score equating to more symptoms
Time frame: Screening (Baseline), Day 1 Visit, and weeks 4, 14, and 24
Change in proptosis
Hertel exophthalmometry will be used to measure the globe position of the eye by calculating the distance from the lateral orbital rim to the surface of the cornea in millimeters (mm)
Time frame: Screening (Baseline), Day 1 Visit, and weeks 4, 14, and 24
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Change in Graves' ophthalmopathy-specific quality-of-life scale (GO-QOL)
The GO-QOL is a self-administered health-related QOL questionnaire specifically designed and validated in patients with TED. It includes 2 subscale GO-QOL scores: (1) visual functioning and (2) appearance-related, with the 2 weighted equally to create an overall score. Both the subscales and overall score are transformed to a scale of 0 to 100, 0 indicating worst health and 100 indicating best health.
Time frame: Screening (Baseline) and weeks 4, 14, and 24
Change in upper eyelid retraction
upper eyelid retraction will be determined by measuring the margin reflex distance (MRD1) in millimeters. The MRD1 is the measurement in millimetres from the light reflex on the patient's cornea to the level of the centre of the upper eyelid margin, with the patient gazing in the primary position.
Time frame: Screening (Baseline), Day 1 Visit, and weeks 4, 14, and 24
Change in lower eyelid retraction
Lower eyelid retraction is measured by the distance from the inferior limbus to the lower eyelid, or by the margin reflex distance 2 (MRD2). The distance between the corneal light reflex to the central portion of the lower eyelid is measured in millimeters
Time frame: Screening (Baseline), Day 1 Visit, and weeks 4, 14, and 24
Change in cell-based functional assays
measured by ELISA
Time frame: Screening (Baseline), Day 1 Visit, and weeks 4,14, and 24