A Randomized Thorough QT Study of Apomorphine Sublingual Film in Patients With Parkinson's Disease
Abstract
A randomized thorough QT study was conducted to assess the effects of apomorphine sublingual film (SL-APO) on corrected QT interval (QTc) and other cardiac conduction parameters in patients with Parkinson's disease (PD) and "OFF" episodes. Patients were titrated to an SL-APO dose that resulted in FULL "ON," followed by up to two additional doses (maximum 60 mg), then randomized at the highest tolerated dose to a treatment sequence of SL-APO, placebo, and moxifloxacin (400 mg, positive control) in a three-way crossover design. Changes from baseline in time-matched, placebo-adjusted Fridericia-corrected QTc interval (ΔΔQTcF) and Bazett-corrected QTc interval (ΔΔQTcB) were analyzed from postdose electrocardiograms. Forty patients were randomized and received single doses of study treatments. Upper limits of 90% confidence intervals (CIs) for ΔΔQTcF of SL-APO were below the 10-millisecond regulatory threshold at all prespecified timepoints, demonstrating no clinically significant effect on QTcF. Lower limits of 90% CIs for ΔΔQTcF of moxifloxacin exceeded the 5-millisecond regulatory threshold at all timepoints up to 3 hours, confirming assay sensitivity. SL-APO had no clinically meaningful effects on QTcB, PR/QRS intervals, heart rate, or electrocardiogram-derived morphology (EudraCT identifier: 2016-001762-29; ClinicalTrials.gov identifier: NCT03187301).
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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