Octanoic Acid for Essential Tremor

OBJECTIVE: To determine the maximum tolerated dose of oral octanoic acid (OA) in patients with essential tremor. Further study objectives include the evaluation of the efficacy and tolerability of octanoic acid with escalation doses, as well as the pharmacokinetic and pharmacodynamic profile. STUDY POPULATION: Up to 30 subjects with ethanol-responsive essential tremor (ET) will be included in the study. Subjects will be recruited in groups of 6 per dose level. DESIGN: The study objectives will be tested using a 3+3 dose escalation design. Per dose level, 3 subjects will be recruited, and dose levels will be 8, 16, 32, 64, and 128 mg/kg, with additional 3 subjects at the same level if one of the three subjects exhibits dose limit toxicity. Subjects will undergo a screening visit, followed by a 2 to 3-day inpatient admission during which the study drug OA will be administered. An outpatient follow-up visit will conclude the study. OUTCOME MEASURES: The primary outcome will be measured by evaluating dose-limiting toxicity, which will be reached once 2 or more subjects exhibit a grade 2 adverse event (CTCAE) on the same dose-level, which is related to OA. The dose below the level at which 2 or more grade 2 OA-related adverse events have been observed, will then be defined as maximum tolerated dose (MTD) and the study stopped. Toxicity for the primary outcome will be monitored by an unblinded independent data safety monitoring board (DSMB), who will determine when the primary outcome is reached. Secondary measures will include safety measures such as routine laboratory parameters, EKG measures, vital signs as well as a standardized assessment for signs of intoxication. Additional secondary outcome measures will include efficacy measures such as tremor accelerometry and digital spiral analysis, as well as a standardized clinical tremor rating scale. Furthermore, pharmacokinetic sampling will be performed.