Apomorphine Sublingual Film Compared with Subcutaneous Apomorphine for OFF Episodes in Parkinson’s Disease: An Open-Label, Randomized, Crossover Study
Fabrizio Stocchi,
Olivier Rascol,
Werner Poewe
et al.
Abstract:Background: Apomorphine sublingual film (SL-APO) and subcutaneous apomorphine (SC-APO) have been used for the treatment of OFF episodes in Parkinson’s disease (PD). No study has prospectively compared efficacy and safety of these formulations. Objective: To compare SL-APO with SC-APO for treatment of OFF episodes in PD. Methods: An open-label, randomized, crossover study assessed SL-APO versus SC-APO in patients with PD and OFF episodes (N = 113). Doses were optimized in randomly assigned order. SL-APO dose in… Show more
“…Safety findings from the dose-optimization phase of this study are provided in a companion article. 9 During SL-APO dose optimization, ⩾1 AE was reported by 64 (62.7%) patients. The most common (⩾5%) AEs were nausea [31.4% (n = 32)], dizziness [9.8% (n = 10)], somnolence [8.8% (n = 9)], dyskinesia [7.8% (n = 8)], and fatigue [5.9% (n = 6)].…”
Section: Resultsmentioning
confidence: 98%
“…A European multicenter, open-label, randomized, crossover study (EudraCT: 2016-003456-7; Clinical Trials register -Search for eudract_number:2016-003456-70), conducted between December 2018 and August 2021, evaluated SL-APO compared with subcutaneous apomorphine (SC-APO) in patients with PD and OFF episodes. Full study design details are provided in a companion article 9 and described briefly herein. The study included an open-label dose-optimization phase and treatment phase; however, the current analysis is non-comparative and describes the outcomes of the dose-optimization phase with SL-APO only.…”
Section: Methodsmentioning
confidence: 99%
“…Full eligibility criteria are provided in a companion article 9 (Supplemental Table 1 unpublished data). Briefly, adults with PD responsive to and being treated with stable doses of carbidopa/levodopa (CD/LD) and any additional PD medications for ⩾4 weeks (>8 weeks for monoamine oxidase-B inhibitors) were enrolled.…”
Section: Patientsmentioning
confidence: 99%
“…Procedures SL-APO dose optimization was initiated in an open-label design in clinic at 10 mg with patients in a practically defined OFF episode 9 (no antiparkinsonian medication after midnight the night prior; Supplemental Figure 1). Assessments included vital signs [orthostatic blood pressure (BP) and pulse rate, before and 60 min after SL-APO administration].…”
Background: Dose optimization of sublingual apomorphine (SL-APO), a dopamine agonist for the treatment of OFF episodes in patients with Parkinson’s disease (PD), has been performed under clinical supervision in clinical trials. SL-APO may be a candidate for home dosing optimization which would be less burdensome for patients. Objectives: To evaluate the feasibility and safety of home optimization of SL-APO in patients with PD and OFF episodes. Design: A multicenter, randomized, crossover study comparing SL-APO with subcutaneous apomorphine was conducted, comprising an open-label dose-optimization phase and a treatment phase. This non-comparative analysis focuses on the outcomes of the dose-optimization phase with SL-APO only. Methods: Patients with PD and OFF episodes received SL-APO at an initial dose of 10 mg in the clinic (open-label). Further optimization could continue at home in 5 mg increments during subsequent OFF episodes (maximum dose of 30 mg). Optimization and tolerability were assessed daily by patient-reported feedback via telephone. Patients reporting a FULL ON returned to the clinic for a dose-confirmation visit (DCV). In patients with inadequate response as determined during the DCV, the dose could be further optimized at home. Results: Home optimization was continued by 81.4% (83/102) of patients. Of these, 80.7% identified an effective, tolerable dose. Mean time between initial clinic visit and DCV 1 was 6.8 days, and the final optimized dose of SL-APO was 30 mg (mode). In total, 62.7% of patients reported ⩾1 adverse event; the most common included nausea (31.4%), dizziness (9.8%), somnolence (8.8%), dyskinesia (7.8%), and fatigue (5.9%). The safety profile in this study in which most patients performed home dose optimization was consistent with the study utilizing clinic-based optimization. Conclusion: After the first clinic dose, home dose optimization of SL-APO appears feasible in patients with PD and OFF episodes, with most patients identifying their optimal SL-APO dose at home. Trial registration: This study is registered with EudraCT (2016-003456-7): Clinical Trials register – Search for eudract_number:2016-003456-70.
“…Safety findings from the dose-optimization phase of this study are provided in a companion article. 9 During SL-APO dose optimization, ⩾1 AE was reported by 64 (62.7%) patients. The most common (⩾5%) AEs were nausea [31.4% (n = 32)], dizziness [9.8% (n = 10)], somnolence [8.8% (n = 9)], dyskinesia [7.8% (n = 8)], and fatigue [5.9% (n = 6)].…”
Section: Resultsmentioning
confidence: 98%
“…A European multicenter, open-label, randomized, crossover study (EudraCT: 2016-003456-7; Clinical Trials register -Search for eudract_number:2016-003456-70), conducted between December 2018 and August 2021, evaluated SL-APO compared with subcutaneous apomorphine (SC-APO) in patients with PD and OFF episodes. Full study design details are provided in a companion article 9 and described briefly herein. The study included an open-label dose-optimization phase and treatment phase; however, the current analysis is non-comparative and describes the outcomes of the dose-optimization phase with SL-APO only.…”
Section: Methodsmentioning
confidence: 99%
“…Full eligibility criteria are provided in a companion article 9 (Supplemental Table 1 unpublished data). Briefly, adults with PD responsive to and being treated with stable doses of carbidopa/levodopa (CD/LD) and any additional PD medications for ⩾4 weeks (>8 weeks for monoamine oxidase-B inhibitors) were enrolled.…”
Section: Patientsmentioning
confidence: 99%
“…Procedures SL-APO dose optimization was initiated in an open-label design in clinic at 10 mg with patients in a practically defined OFF episode 9 (no antiparkinsonian medication after midnight the night prior; Supplemental Figure 1). Assessments included vital signs [orthostatic blood pressure (BP) and pulse rate, before and 60 min after SL-APO administration].…”
Background: Dose optimization of sublingual apomorphine (SL-APO), a dopamine agonist for the treatment of OFF episodes in patients with Parkinson’s disease (PD), has been performed under clinical supervision in clinical trials. SL-APO may be a candidate for home dosing optimization which would be less burdensome for patients. Objectives: To evaluate the feasibility and safety of home optimization of SL-APO in patients with PD and OFF episodes. Design: A multicenter, randomized, crossover study comparing SL-APO with subcutaneous apomorphine was conducted, comprising an open-label dose-optimization phase and a treatment phase. This non-comparative analysis focuses on the outcomes of the dose-optimization phase with SL-APO only. Methods: Patients with PD and OFF episodes received SL-APO at an initial dose of 10 mg in the clinic (open-label). Further optimization could continue at home in 5 mg increments during subsequent OFF episodes (maximum dose of 30 mg). Optimization and tolerability were assessed daily by patient-reported feedback via telephone. Patients reporting a FULL ON returned to the clinic for a dose-confirmation visit (DCV). In patients with inadequate response as determined during the DCV, the dose could be further optimized at home. Results: Home optimization was continued by 81.4% (83/102) of patients. Of these, 80.7% identified an effective, tolerable dose. Mean time between initial clinic visit and DCV 1 was 6.8 days, and the final optimized dose of SL-APO was 30 mg (mode). In total, 62.7% of patients reported ⩾1 adverse event; the most common included nausea (31.4%), dizziness (9.8%), somnolence (8.8%), dyskinesia (7.8%), and fatigue (5.9%). The safety profile in this study in which most patients performed home dose optimization was consistent with the study utilizing clinic-based optimization. Conclusion: After the first clinic dose, home dose optimization of SL-APO appears feasible in patients with PD and OFF episodes, with most patients identifying their optimal SL-APO dose at home. Trial registration: This study is registered with EudraCT (2016-003456-7): Clinical Trials register – Search for eudract_number:2016-003456-70.
“…The study included both patients who had not previously participated in a study with SL-APO (defined as ‘de novo patients’; i.e. patients de novo to SL-APO treatment, not de novo PD patients) as well as ‘rollover patients’ who had completed SL-APO studies CTH-201 (phase 2) [ 26 ], CTH-203 (phase 2) [ 27 ], CTH-300 (phase 3) [ 24 ], or CTH-302 (phase 3) [ 28 ]. Fig.…”
Background
Apomorphine sublingual film (SL-APO) is an on-demand treatment for OFF episodes in patients with Parkinson’s disease (PD).
Objective
To assess the long-term (≥ 3 years) safety/tolerability and efficacy of SL-APO.
Methods
Study CTH-301 (http://www.clinicaltrials.gov NCT02542696; registered 2015-09-03) was a phase 3, multicentre, open-label study of SL-APO in PD patients with motor fluctuations, comprised of a dose-titration and long-term safety phase. All participants received SL-APO. The primary endpoint was safety/tolerability (treatment-emergent adverse events [TEAEs]) during the long-term safety phase. Efficacy assessments included the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III (motor examination), assessed at weeks 24, 36 and 48 during the first year of the long-term safety phase.
Results
496 patients were included and 120 (24.2%) completed the long-term safety phase. Mean duration of SL-APO exposure was 294.3 days. TEAEs related to study drug were experienced by 65.3% of patients (most common: nausea [6.0%], stomatitis [1.8%], lip swelling [1.8%], dizziness [1.6%], oral mucosal erythema [1.6%], mouth ulceration [1.6%]). TEAEs leading to study drug withdrawal were experienced by 34.0% of patients (most common: nausea [5.4%], lip swelling [4.5%], mouth ulceration [2.6%], stomatitis [2.3%]). A clinically meaningful reduction in MDS-UPDRS part III score was observed as soon as 15 min following administration of SL-APO, with peak effects observed approximately 30 min post-dose and sustained up to 90 min post-dose; results were consistent over 48 weeks.
Conclusions
SL-APO was generally well tolerated and efficacious over the long term as an on-demand treatment for OFF episodes in patients with PD.
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