Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Sep;11(9):1068-1077.
doi: 10.1002/cpdd.1147. Epub 2022 Jul 28.

A Randomized Thorough QT Study of Apomorphine Sublingual Film in Patients With Parkinson's Disease

Fabrizio Stocchi  1 , Elizabeth L Peckham  2 , Maria Francesca De Pandis  3 , Ken Sciarappa  4 , Robert Kleiman  5 , Felix Agbo  6 , C Warren Olanow  7   8 , David Blum  4 , Bradford Navia  4
Affiliations
Randomized Controlled Trial

A Randomized Thorough QT Study of Apomorphine Sublingual Film in Patients With Parkinson's Disease

Fabrizio Stocchi et al. Clin Pharmacol Drug Dev. 2022 Sep.

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).

Keywords: Parkinson's disease; QT interval; apomorphine sublingual film; pharmacokinetics; “OFF” episodes.

PubMed Disclaimer

Conflict of interest statement

F.S. and E.L.P. received research/grant support from Sunovion Pharmaceuticals Inc. for participation in this study. M.F.D.P. reports no conflicts of interest. K.S. and F.A. are full‐time employees of Sunovion Pharmaceuticals Inc. and may hold stock/stock options in the company. R.K. is an employee of eResearch Technology Inc. (ERT) and performs consulting services for various pharmaceutical companies, including Sunovion Pharmaceuticals Inc., for which ERT receives payment. C.W.O. owns shares in Clintrex Research Corporation, which has received fees from Sunovion Pharmaceuticals Inc. D.B. and B.N. were employees of Sunovion Pharmaceuticals Inc. at the time the study was conducted.

Figures

Figure 1
Figure 1
Patient disposition. AE, adverse event; ECG, electrocardiogram, PK, pharmacokinetics.
Figure 2
Figure 2
Mean changes from baseline in QTcF with (A) apomorphine sublingual film/placebo/moxifloxacin, (B) apomorphine sublingual film (time‐matched/placebo‐adjusted), and (C) moxifloxacin (time‐matched/placebo‐adjusted). CI, confidence interval; QTcF, Fridericia‐corrected QTc interval.
Figure 3
Figure 3
Mean apomorphine plasma concentration–time profiles by dose. aNumber of patients who received the indicated dose of apomorphine sublingual film.
See this image and copyright information in PMC

References

    1. Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. JAMA. 2020;323(6):548‐560. - PubMed
    1. Marras C, Beck JC, Bower JH, et al. Prevalence of Parkinson's disease across North America. NPJ Parkinsons Dis. 2018;4:21. - PMC - PubMed
    1. Olanow CW, Stocchi F. Levodopa: a new look at an old friend. Mov Disord. 2018;33(6):859‐866. - PubMed
    1. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease. Neurology. 2009;72(21 Suppl 4):S1‐S136. - PubMed
    1. Chou KL, Stacy M, Simuni T, et al. The spectrum of “OFF” in Parkinson's disease: what have we learned over 40 years? Parkinsonism Relat Disord. 2018;51:9‐16. - PubMed

Publication types

Associated data