Safety Assessments
anxiety, palpitations, tremor, ICH, thyroid dysfunction, thyrotoxic, insomnia, rhythm abnormalities, suicidality, Cancer
ADVERSE EVENTS, THYROID DYSFUNCTION, ADVERSE EFFECTS, HYPERTHYROID SYMPTOM, CANCER
During the screening visit, participants had lab work done (thyroid stimulating hormone [TSH], comprehensive metabolic panel, urine pregnancy test) to assess for study eligibility criteria. Serum thyroid function tests (TSH, free thyroxine [T4], and T3) were repeated at every study visit moving forward. Participants also underwent blood chemistry testing at weeks 6, 12, 18, and 24.The following pre-defined study drug dosing algorithm was used if thyroid dysfunction (clinical or bio-chemical) was detected during the study: (A) symptoms of anxiety, tremor and insomnia led to a dose reduction to former dose irrespective of the serum T3 level. If symptoms persisted 1 week after dose reduction, another dose reduction was implemented; (B) palpitations were evaluated with an electrocardiogram (ECG) to assess for rhythm abnormalities and then managed with a dose reduction regardless of ECG findings. If symptoms persisted after 1 week, another dose reduction was done; and (C) if a subject’s serum TSH dropped to < 0.5 mU/L and/or serum T3 was greater than 10% above the upper limit of normal, the study drug dose was reduced to the subject’s previously-administered dose. Additional pre-defined monitoring for adverse effects (AEs) was performed throughout the study including assessing vital signs (pulse rate, blood pressure, and temperature), weight, and urine pregnancy test every 6 weeks, and subjects completed a hyperthyroid symptom scale (HSS) score to assess for thyrotoxic symptoms at weeks 3, 9, 15, and 21. The HSS score was collected between the in-person study visits for additional safety monitoring [In compliance with the FDA regulations on assessing for suicidality in prospective trials, the Columbia Classification Algorithm for Suicide Assessment was administered at all in-person study visits.All safety data were recorded per International Conference on Harmonization (ICH) Guideline for Good Clinical Practice E6(R1) and all AEs were graded based on the National Cancer Institute’s Common Terminology Criteria for AEs (version 4.0). In order to adhere to the ICH guidelines for reporting serious adverse events (SAE), the IRB was notified within 24 hours of the study staff becoming aware of a SAE.The study drug was to be permanently discontinued for one or more of the following pre-defined reasons: (A) if a participant developed intolerable thyrotoxic symptoms, (B) if a participant’s thyroid function tests remain abnormal despite dose reduction of study drug, (C) if the participant became pregnant or suicidal, (D) if the participant experienced a grade 3 or higher AE that was reported as possibly related to the study drug, and (E) if the participant or treating physician wanted to prematurely withdraw them from the study.The data safety monitoring board consisted of two endocrinologists (JSRM and DSC) and one neurologist (EMM). The DSMB met on a predetermined schedule (every 6 months until completion of the trial) and any time an SAE occurred.