Industrie Poster

Autor: Dr. Jakkoo Kopra, AbbVie Deutschland GmbH
Ko-Autor:innen: Martin Südmeyer, David Pedrosa, Frank Siebecker, Carolin Arlt, Jaakko Kopra, Wolfgang Jost
Topic: Diagnostische Verfahren

Abstract:
Introduction: Making informed decisions to aid timely management of Parkinson’s Disease (MANAGE PD) is a registered web-based (managepd.eu) medical device to assist physicians identify insufficiently controlled Parkinson’s patients. The tool categorizes patients based on a validated algorithm. In category (cat) 1 patients’ symptoms are well controlled under the current treatment. In cat 2 patients may benefit from further oral treatment optimization and in cat 3 patients may benefit from device-aided therapies (DAT).

Objective: To investigate the utility of the MANAGE PD tool in routine clinical care in Germany and the planned next steps after the tool recommendation. Methods: This cross-sectional, non-interventional study was conducted in 19 neurology centers in Germany. The study population consisted of patients diagnosed with PD who attended a routine visit during which all data were collected. The first section of the questionnaire was independently filled out by both the patient and the physician. The data were analyzed and presented using descriptive statistics.

Results: Of 278 patients, 18,0% were assigned to cat 1; 45,0% to cat 2; and 37,1% to cat 3 using the tool. The physician’s assessment of the categories was 27%; 48% and 26%; respectively. The agreement between the physician’s and patient’s responses in section 1 was high. Changes in treatment were planned for 47% of patients in cat 2 and 62% in cat 3. DAT was planned for 35% of patients in cat 3. The most common reasons for not planning treatment change were patient not wanting change, other, and no change needed. The most common personal reasons for not initiating DAT were fear and invasiveness.

Conclusion: The high level of agreement between the patient and the physician suggests that patients can report reliable and useful information regarding their motor state. However, their reluctance concerning the recommended treatment optimization was high.

Autorin: Dr. rer. nat. Nadine Brehm, AbbVie Deutschland GmbH 
Ko-Autor:innen: Jason Aldred, Tove Henriksen, Manon Bouchard, Juan Carlos Martínez-Castrillo, Michael J. Soileau, Amy Spiegel, Lars Bergmann, Resmi Gupta, Pavnit Kukreja, David G. Standaert
Topic: M. Parkinson

Abstract: 
Background: As Parkinson’s disease (PD) progresses, patients increase the number and classes of medications to control motor fluctuations. However, even those compliant with complex regimens can develop poor motor control. Foslevodopa/foscarbidopa (LDP/CDP) delivered 24 hours/day improves motor fluctuation and dyskinesia in patients with PD. 

Objective: Report efficacy and safety profiles of patients on sustained LDP/CDP continuous subcutaneous infusion (CSCI) mono- or polytherapy from three phase 3 clinical trials. 

Methods: Post-hoc analysis assessed patients with PD on sustained mono- or polytherapy in three LDP/CDP clinical trials, including: a randomized 12-week double-blind comparison of LDP/CDP CSCI versus oral LD/CD (NCT04380142), a single-arm 52-week open-label study of LDP/CDP CSCI (NCT03781167), and an open-label extension of the 52-week trial for up to 96-weeks (NCT04379050). Sustained monotherapy was defined as no concomitant PD medications during LDP/CDP therapy (except in case of rescue in 12-week trial). 

Results: Sustained LDP/CDP monotherapy was experienced by 25.7% of 74 patients treated with LDP/CDP in the 12-week, 20.1% of 244 patients in the 52-week, and 35.7% of 129 patients in the 96-week trials. Consistent with previous results, both mono- and polytherapy LDP/CDP groups demonstrated significant improvements vs baseline in “On” time without troublesome dyskinesia and “Off” time compared to oral, with additional improvements vs baseline in key secondary endpoints also observed in the 12-week study. All outcomes in the 52-week trial showed significant improvement vs baseline with mono- and polytherapy. The 96-week extension trial with continued LDP/CDP therapy showed stable outcomes in both groups. Safety of mono- and polytherapy was similar in LDP/CDP-treated patients, with fewer events in the 12-week monotherapy group. 

Conclusions: In mono- and polytherapy-treated patients receiving LDP/CDP CSCI, comparable efficacy and safety profiles were demonstrated across three phase 3 clinical trials. Thus, LDP/CDP monotherapy is achievable and can be considered a viable treatment option comparable to polytherapy. 

Autorin: Dr. rer. nat. Nadine Brehm, AbbVie Deutschland GmbH
Ko-Autor:innen: Drew S Kern, Stuart H Isaacson, Sara Dhanani, Jason Aldred, Bruno Bergmans, Diego Santos-Garcia, Tomoko Oeda, Florin Gandor, Pavnit Kukreja, Lars Bergmann, Resmi Gupta, Saritha Talapala, Amy M Spiegel, Thomas E Kimber
Topic: M. Parkinson

Abstract:
Background: Foslevodopa/foscarbidopa (LDP/CDP) is a highly soluble formulation of levodopa/carbidopa prodrugs delivered as continuous (24-hour/day) subcutaneous infusion. Data from a 12-week, double-blind, double-dummy study suggest that safety events occur more frequently in the first few weeks after LDP/CDP initiation compared to the subsequent maintenance period. 

Objective: Evaluate frequency of adverse events over time with LDP/CDP in patients with advanced Parkinson’s disease (PD) in a phase 3, open-label safety trial over 52 weeks. 

Methods: Post hoc analysis of third interim results from a 52-week, phase 3, open-label, single-arm trial (NCT03781167) of LDP/CDP in levodopa-responsive idiopathic PD patients whose symptoms were inadequately controlled by current therapy (≥2.5 average “Off” hours/day). Individualized doses of LDP/CDP were titrated to optimally control motor symptoms during a 4-week optimization-period, and optimized doses were maintained for the remainder of treatment period (48-week maintenance-period). Adverse events (AEs) were recorded during the 4-week optimization-period in daily/weekly intervals and during the 48-week maintenance-period in either 8-week (weeks 5–13) or 12-week (weeks 14–26, 27–39, and 40–52) intervals. AEs were classified as systemic or infusion site AEs. 

Results: A total of 244 patients received LDP/CDP. Most patients reported AEs that were non-serious (n=181, 74.2%) and mild (n=50, 20.5%) to moderate (n=117, 48.0%) in severity. When evaluated over time, the proportion of patients who reported infusion site AEs and systemic AEs was higher in the 4-week optimization-period than during the maintenance-period. Patients who discontinued LDP/CDP (n/N=66/107, 61.7%) did within the first 10 weeks of treatment. 

Conclusion: Most adverse events and discontinuations occurred within the first 10 weeks of study (including during the 4-week optimization-period), which was the time period healthcare providers and patients were learning about the delivery system. Patient education before and during LDP/CDP treatment may help to minimize AEs, thereby improving treatment adherence.

Autorin: Dr. rer. nat. Nadine Brehm, AbbVie Deutschland GmbH
Ko-Autor:innen: Per Odin, Thomas E Kimber, Bruno Bergmans, Eric Freire-Alvarez, Florin Gandor, Stuart H Isaacson, Sara Dhanani, Robert A Hauser, Marie O’Meara, Anna Jeong, Jia Jia, Resmi Gupta, Lars Bergmann, Megha Shah, Linda Harmer, Saritha Talapala, Jason Aldred
Topic: M. Parkinson

Abstract:
Background: LDP/CDP is a formulation of levodopa/carbidopa prodrugs delivered as a continuous (24-hour/day) subcutaneous infusion. Phase 3 studies indicate LDP/CDP has a favorable benefit-risk profile, with systemic safety generally consistent with that of oral LD/CD. Infusion site reactions (ISRs) were the most common AEs. As with other subcutaneous therapies, ISRs may reflect localized inflammatory reactions although infusion site infections are also reported. The majority of such events were non-serious, mild to moderate in severity and resolved. 

Objective: To characterize reported infusion site infection adverse events (AEs) and their clinical management in patients with Parkinson’s disease (PD) treated with foslevodopa/foscarbidopa (LDP/CDP). 

Methods: This integrated post-hoc analysis summarizes AEs reported by investigators as presumed infusion site infection under the terms infection, cellulitis, and/or abscess in patients with advanced PD who received LDP/CDP during phase 3 clinical trials. Four trials were included: a 12-week, phase 3, randomized, double-blind trial (NCT04380142); a 52-week, phase 3, open-label, single-arm trial (NCT03781167); and their 2 open-label extension studies (NCT04379050 and NCT04750226). 

Results: 379 patients were treated with LDP/CDP. Investigators reported AEs of infusion site infection, cellulitis, and/or abscess in 145 (38.3%) patients; the majority were reported as non-serious, mild to moderate in severity and resolved. Despite clinically presumed infection, infusion site culture was infrequently performed and uncommonly identified any bacterial pathogen. Of patients with reported infusion site infection, cellulitis, and/or abscess, 115 (79.3%) received primarily empiric antibiotic therapy and 20 (13.8%) had incision and drainage. Only 24 patients (16.6%) with reported infections discontinued treatment with LDP/CDP due to the events.

 Conclusion: Although infusion site events were the most common AEs reported in patients who received LDP/CDP, the majority were non-serious, mild to moderate in severity and resolved. Most presumed infusion site infections were managed with empiric oral antibiotics and did not lead to discontinuation of therapy.

Autorin: Dr. rer. nat. Nadine Brehm, AbbVie Deutschland GmbH
Ko-Autor:innen: Victor SC Fung, Jason Aldred, Filip Bergquist, Erik H. Danielsen, Anna Jeong, Jia Jia, Amy Spiegel, Saritha Talapala, Camille Carroll
Topic: M. Parkinson

Abstract:
Background: Foslevodopa/foscarbidopa (LDP/CDP) is a soluble formulation of levodopa/carbidopa prodrugs administered as 24-hour/day continuous subcutaneous infusion (CSCI). A 52-week, open-label phase 3 study, LDP/CDP demonstrated a favorable risk/benefit profile in patients with aPD (NCT03781167); those who completed the parent-trial were eligible to enroll in an OLE (NCT04379050). 

Objective: To evaluate long-term safety/tolerability of LDP/CDP in patients with advanced Parkinson’s disease (aPD) in a phase 3 open-label extension (OLE) study. 

Methods: The ongoing OLE consists of a 96-week Primary-Treatment-Period and optional Extended-Treatment-Period. LDP/CDP infusions are individually optimized (600–4250 mg LD equivalents/24 hours). Primary endpoint is safety/tolerability. Key secondary endpoints are change from OLE baseline for mean normalized daily “Off” and “On” times and morning akinesia. Efficacy data are presented through Week 84. 

Results: 137 patients completed the parent-study, 129 (94.2%) enrolled in OLE; 113 (87.6%) are currently ongoing. Most common reason for discontinuation was treatment-emergent adverse events (AE; 8 [6.2%]). At OLE baseline, most patients are male (63.6%), White (86.8%), with a mean (SD) age of 63.1 (9.2) years, time since PD diagnosis of 10.2 (4.9) years, and “Off” time of 2.53 (2.9) hours. Mean person-years of study drug exposure (parent-study and OLE) is 314.0 years, with a mean (SD) exposure duration of 470.1 (386.9) days. Overall, 83.7% of patients experienced ≥1 AE; most were non-serious and mild or moderate in severity. “Off” and “On” times were generally stable through Week 84 in OLE (“On” time without troublesome dyskinesia −0.6 [2.9] hours, P=.252); “On” time with troublesome dyskinesia (−0.2 [1.2] hours, P=.364); “Off” time (+0.9 [2.7] hours, P=.102). At Week 84, 75% of patients reported awakening in “On” state (n/N= 15/20). 

Conclusions: Long-term CSCI of LDP/CDP was generally safe, well tolerated and effected sustained improvements in motor fluctuations and morning akinesia that were consistent with parent-study.

Autor: Dr. rer. nat. Nadine Brehm, AbbVie Deutschland GmbH
Ko-Autor:innen: Yi Rang Han, Hari Kalluri, Anna Jeong, Charles Locke, Maurizio F. Facheris, Shelly V. Gupta, Matthew Rosebraugh, Nadine Brehm
Topic: M. Parkinson

Abstract:
Background: Foslevodopa/foscarbidopa is a soluble formulation of levodopa(LD)/carbidopa(CD) prodrugs delivered as continuous (24-hour/day) subcutaneous (SC) infusion, providing consistent therapeutic levels of LD, mitigating the shortcomings of the progressive reduced effectiveness of oral LD. Although SC infusions are typically administered to the abdomen, patients may prefer or need to consider alternative infusion sites. This work characterizes the LD/CD pharmacokinetics (PK) following foslevodopa/foscarbidopa SC infusion to arm, thigh and flank compared to the abdomen. 

Objective: To characterize safety/tolerability and PK of LD and CD after delivery of foslevodopa/foscarbidopa in PD patients at 4 different SC infusion sites. 

Methods: Patients with LD-responsive PD were confined for approximately 12 days, following standardized procedures. Foslevodopa/foscarbidopa was infused consecutively in each of the designated SC sites in a 4-way randomized crossover design, 48 hours/site. Serial plasma samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. PK parameters including average concentration, degree of fluctuation and swing were compared among arm, thigh, flank and the reference abdomen SC infusion regimen. 

Results: LD and CD showed similar PK based on average concentrations of arm, thigh, flank compared to the reference abdomen regimen. The coefficient of variation for average concentration ratios was similar between sites of administration and all less than 10%. For both LD and CD, mean degree of fluctuation and mean swing values were comparable across infusion sites with 90% confidence intervals of the ratios of arm, thigh and flank over abdomen containing 1.0. Adverse events (AEs) were non-serious and mild to moderate in severity including skin related AEs with frequency and severity being similar across infusion sites.

Conclusions: Pharmacokinetics of foslevodopa/foscarbidopa is not sensitive to SC site of administration. Abdomen, arm, thigh, and flank may be suitable and interchangeable sites for SC delivery for foslevodopa/foscarbidopa. 

Autor: Dr. Michael Kemmer, Bial Deutschland GmbH
Ko-Autor:innen: Jee-Young Lee, Joaquim J. Ferreira, Hyeo-il Ma, José-Francisco Rocha, Beomseok Jeon, on behalf of Korean OGT_001 study investigators
Topic: Pharmakotherapie

Abstract:
Objective: This study aimed to explore the efficacy of opicapone (OPC)-50mg or an extra dose of levodopa (L-DOPA)-100mg to treat wearing-off in patients with Parkinson’s disease (PD). BACKGROUND: OPC proved to be effective for end-of-dose motor fluctuations in L-DOPA/dopa decarboxylase inhibitor (DDCi) treated patients with PD.

Methods: Prospective, multicenter, randomized, active-controlled (L-DOPA-100mg) and 4-week study. One-hundred and sixty-nine (169) PD patients were randomly assigned (1:1) to OPC-50mg once-daily (n=88) or L-DOPA-100mg (n=81). A 1-week screening-period was followed by a 4-week maintenance-phase. Primary endpoint was change from baseline in absolute OFF-time. Secondary endpoints include tolerability, Movement-Disorder-Society-Unified-PD-Rating-Scale (MDS-UPDRS), 8-item PD Questionnaire (PDQ-8) and clinical-global-impression of improvement/change (CGI-I, PGI-C).

Results: At week 4, mean(SE) change from baseline in absolute OFF-time of -62.1min (9.8) for OPC-50mg and -16.7min (10.0) for L-DOPA-100mg, resulted in a significant difference of -45.4min (p-value: 0.0015). No significant differences were observed for MDS-UPDRS and PDQ-8 between groups. OPC-50mg treated patients tended to show higher percentage of improvement in both CGI-I/PGI-C. OPC was generally well tolerated, but adverse-event (AE) was more frequent for OPC-50mg (37.9% vs 18.5% in L-DOPA-100mg) with dyskinesia (6.9%) as the most common AE.

Conclusions: Opicapone 50mg can be considered a potential first line therapy to treat wearing-off versus the standard L-DOPA approach.

Autor: Dr. Michael Kemmer, Bial Deutschland GmbH
Ko-Autor:innen: Joaquim Ferreira, Olivier Rascol, Fabrizio Stocchi, Angelo Antonini, Joana Moreira, Guillermo Castilla-Fernández, José-Francisco Rocha, Joerg Holenz, Werner Poewe
Topic: Pharmakotherapie

Abstract:
Introduction: Opicapone (OPC) has proven to be generally well-tolerated and efficacious in reducing OFF-time in L-DOPA/DDCi treated patients with Parkinson’s disease (PD) and end-of-dose motor fluctuations. This study aimed to explore the potential of OPC to enhance the clinical benefit of L-DOPA/DDCi in PD patients without motor complications. 

Methods: This was a double-blind, multicenter, randomized, placebo-controlled study. Three-hundred and fifty-five (355) PD patients were randomly assigned (1:1) to OPC-50mg once-daily or placebo. A 4-week screening-period was followed by a 24-week maintenance phase. The primary efficacy endpoint was the change from baseline to week-24 in MDS_UPDRS-III. Secondary endpoints included tolerability, clinical global impression of improvement (CGI-I, both patient and clinician) and MDS_UPDRS-IV. 

Results: At week-24, the mean(SE) change from baseline in MDS_UPDRS-III score for the OPC-50mg arm was -6.5(0.7) versus -4.3(0.7) for the placebo arm resulting in a significant difference of -2.2(0.9) favouring OPC-50mg (p-value=0.010). A significantly higher proportion of OPC-treated patients reported an improvement in their clinical condition (58% vs 46% in placebo, as assessed by patient PGI-I). A similar trend, but not significant, was observed for the CGI-I (50% vs 46% in placebo). Fewer OPC-50mg treated patients (5.5% vs 9.8% in placebo) reported motor complications in MDS_UPDRS-IV (0.3 points vs 0.4 in placebo). The frequency and types of adverse events reported were similar between OPC-treated and placebo-treated patients. 

Conclusion: The addition of adjunct opicapone in levodopa-treated PD patients without motor complications significantly improved motor function.

Autor: Dr. Michael Kemmer, Bial Deutschland GmbH
Ko-Autor:innen: Luís Magalhães, Miguel M. Fonseca, Guillermo Castilla-Fernández, Raquel Costa1, David K. Simon, Joerg Holenz, Nuno Mendonça
Topic: Pharmakotherapie

Abstract:
Objective: To assess the efficacy of BIA 28-6156 in delaying clinically meaningful motor progression in PD patients who have a PD-risk associated variant in the GBA1 gene. Safety and tolerability of BIA 28-6156 also will be investigated. 

Background: Heterozygous GBA1 pathogenic variants are the most common genetic risk factor for PD, accounting for 5-15% of PD patients. On average, GBA-PD patients present a clinically distinct course with an earlier age of onset and higher rate of disease progression with faster cognitive impairment as compared with idiopathic PD patients [1]. Data from previous studies with BIA 28-6156, an allosteric activator of the enzyme GCase, in GBA-PD patients are consistent with GCase activation [2]. 

Methods: Phase 2, multicenter, randomized, double-blind (DB), placebo-controlled study, with Part A (genetic screening) and Part B (DB treatment up to 78 weeks). Approximately 237 genetically confirmed GBA-PD adult patients will be randomized in a 1:1:1 allocation ratio to BIA 28-6156 10 mg/day, BIA 28-6156 60 mg/day, or matching placebo. Clinical diagnosis of PD for at least 1 to 7 years, a modified H&Y score ≤2.5, and a MoCA score ≥22 are required for inclusion. Patients must be receiving a stable dose of PD medication for at least 30 days before screening (Part B) and will continue receiving usual PD medications throughout the study. Patients with a LRRK2 pathogenic variant will not be eligible to participate. 

Results: Primary endpoint is time from baseline to first clinically meaningful progression on motor aspects of experiences of daily living, as assessed by ≥2-points increase in MDS-UPDRS Part II and no improvement (≥0-points) in MDS-UPDRS Part III. Secondary endpoints include safety, tolerability, time from baseline to first increase of ≥5-points in MDS-UPDRS Part III, worsening on the CGI-C, PGI-C and first LEDD increase. Change from baseline to Week 78 in the MDS-UPDRS Parts I-IV, modified H&Y scale, PD-CRS score, PDQ-39 and EQ-5D-5L scores will be investigated. 

Conclusions: This time-to-event study will evaluate the efficacy and safety of a once-daily GCase activator, BIA 28-6156, as a disease-modifying therapy for GBA-PD patients.

Autor: Dr. Michael Kemmer, Bial Deutschland GmbH
Ko-Autor:innen: W. Jost, M. Coelho, M. Fonseca, G. Castilla-Fernández, D. Magalhães, C. Denecke Muhr
Topic: Pharmakotherapie

Abstract:
Objective: To assess the occurrence of orthostatic hypotension (OH) during apomorphine sublingual film (SL-APO) dose-optimization in patients with Parkinson’s disease (PwPD). 

Background: SL-APO has been shown to be an effective and generally well-tolerated on-demand treatment for OFF episodes in PwPD [1,2]. Several dopamine agonists have been associated with orthostatic hypotension. 

Methods: In two pivotal trials (CTH-300 and CTH-302) SL-APO was optimized in PwPD and OFF episodes to obtain an effective and tolerable dose. Patients’ blood pressure was measured before and 1h after SL-APO intake when they visited clinics during the dose-optimization phase. We post-hoc analyzed OH-related treatment-emergent adverse events (TEAEs), BP readings, and their co-occurrence. 

Results: At 652 dose-optimization visits from 240 patients, mean BP readings before and after SL-APO intake were comparable. In these visits, the frequency of OH appearing after SL-APO intake was similar to the frequency of OH occurring at pre-dosing only. Correspondingly, visits with reported OH-related TEAEs (5.4% of total visits) were accompanied by OH, based on BP readings, at a comparable frequency before and after SL-APO intake only.

Conclusion: Overall, SL-APO did not affect general BP readings nor the frequency of OH as assessed by those readings during dose-optimization at in-clinic visits (co-occurring with or without reported OH-related TEAEs). 

Autor: Dr. Michael Kemmer, Bial Deutschland GmbH
Ko-Autor:innen: Joaquim J. Ferreira,, Werner Poewe, Olivier Rascol, Fabrizio Stocchi, Angelo Antonini, Joana Moreira, Bruno Guimarães, José-Francisco Rocha
Topic: Pharmakotherapie

Abstract:
Introduction: Optimising levodopa (LD) treatment regimens through the inhibition of catechol-O-methyltransferase (COMT) is an effective strategy in the management of motor fluctuations (MF) in patients with Parkinson’s disease (PD). Study 203 demonstrated that adding the COMT inhibitor opicapone (OPC) to LD therapy increases LD systemic exposure and decreases OFF-time in patients with PD and MF. This post-hoc analysis evaluated the OFF/ON patterns in patients included in Study 203. 

Methods: Study 203 was an exploratory, open-label, modified cross-over trial. All participants received LD/carbidopa (CD) 500/125 mg, administered as 5 daily intakes of 100/25 mg every 3 hours for 2 weeks and were then randomly (1:1) assigned to LD/CD 400/100 mg given in 4 or 5 daily intakes plus OPC 50 mg for 2 additional weeks. LD 12-hour pharmacokinetics (PK) was the primary outcome (last daily intake was excluded from the PK analysis);12-hour patient ON/OFF monitoring was a key secondary outcome. This study evaluated ON/OFF patterns in patients treated with the LD/CD 500/125 mg regimen before randomisation. 

Results: Overall, 24 patients were recruited and received the LD/CD 500/125 mg regimen (Table). For all daily intakes, the mean total ON-time was 5h 48mins and the mean total OFF-time was 6h 3mins (Figure). The total OFF-time was divided into time-to-ON (2h 52mins) and ‘wearing-off’ (3h 23mins), which represented 47.3% and 55.8% of the total OFF-time, respectively. 

Conclusions: This post-hoc analysis suggests that nearly half of the overall OFF-time in LD-treated patients with PD and motor fluctuations is time to reach ON-state.

Autor: Dr. Michael Kemmer, Bial Deutschland GmbH
Ko-Autor:innen: K Ray Chaudhuri, Per Odin, Joaquim Ferreira, Angelo Antonini, Olivier Rascol, Mónica Kurtis, Alexander Storch, Kirsty Bannister, Raquel Costa, Diogo Magalhães, José Francisco Rocha, Patrício Soares-da-Silva
Topic: Pharmakotherapie

Abstract:
Introduction: Pain associated with end-of-dose motor fluctuations (MF) is commonly reported in levodopa (L-dopa)-treated patients with Parkinson’s disease (PD) and has a negative impact on patients’ quality of life. There is evidence that dopaminergic therapies can alleviate pain in PD; however, high-quality evidence is lacking. Opicapone (OPC) proved effective for the treatment of end-of-dose MF in patients with PD in two large clinical trials. The OCEAN study aims to evaluate if treatment with OPC can improve MF-related pain. 

Methods: The OCEAN study is a double-blind, randomised, placebo-controlled trial that aims to recruit ~140 patients (≥30 years old) with idiopathic PD, who were treated with 3−8 daily oral doses of L-dopa/ dopa decarboxylase inhibitor (DDCI) and experienced pain associated with end-of-dose MF. Patients will be randomised (1:1) to OPC 50 mg once daily or placebo during a 24-week follow-up period (Figure 1A). 

Results: The primary endpoint is change from baseline in domain 3 (fluctuation-related pain) of the King’s-Parkinson’s-Disease-Pain-Scale (KPPS). Secondary endpoints include tolerability (treatment-emergent adverse events), motor and non-motor symptoms (Figure 1B). The study received approval in Germany, Italy, Portugal, Spain and the UK. Six sites are actively recruiting and 37 site-initiation-visits have been performed. As of December 2022, XX patients have been randomised and at least XX have completed the study. 

Conclusion: This study will evaluate the benefit of once-daily OPC 50 mg as adjunct to L-dopa therapy on MF-related pain in patients with PD.

Autor: Prof. Dr. med. Jan Kassubek, Klinik für Neurologie der Universität Ulm
Ko-Autor:innen: Stuart H. Isaacson, Rajesh Pahwa, Eric Pappert, Stacy Wu, Carmen Denecke Muhr
Topic: Pharmakotherapie

Abstract:
Objective: To compare the safety profile of clinic versus home dose optimization of apomorphine sublingual film (SL-APO) in patients with Parkinson’s disease experiencing OFF episodes. 

Background: In previous SL-APO clinical studies, both initiation and dose optimization were performed entirely in a clinical setting to assess tolerability, including potential orthostatic hypotension-related syncope. 

Methods: In the SL-APO pivotal study, both open-label dose initiation and optimization (10‒35 mg; 5-mg increments) occurred entirely in clinic [1]. In a separate crossover study comparing SL-APO and subcutaneous apomorphine, both drugs were initiated and optimized sequentially in a random fashion (randomized to SL-APO first, n=57) [2]. SL-APO was initiated at 10 mg in a clinical setting, while dose optimization (15‒30 mg; 5-mg increments) could continue at home without direct supervision (performed by 81% of patients) until the patient felt an optimal response was achieved; optimal dose was confirmed by the investigator in clinic. Treatment-emergent adverse events (TEAEs) reported during dose optimization of each study are presented. 

Results: Comparable percentages of patients in the pivotal (N=141) and crossover (N=102) studies reported ≥1 TEAE (58% vs 63%, respectively) during SL-APO dose optimization. A higher percentage of pivotal study patients versus crossover study patients reported severe TEAEs (9% vs 2%) and TEAEs leading to drug withdrawal (9% vs 4%). Fewer patients experienced orthostatic hypotension in the pivotal study versus the crossover study (1% vs 4%). Presyncope and syncope were experienced by 1% of patients each in the pivotal study and by no crossover study patients. Nausea was the most frequently reported TEAE in the pivotal (21%) and crossover studies (31%) and the most frequent TEAE leading to drug withdrawal, with a similar incidence in both studies (2.1% vs 2%, respectively). Comparable percentages of patients in both the pivotal and crossover studies reported dizziness, somnolence, and fatigue. Fewer pivotal study versus crossover study patients reported dyskinesia. 

Conclusions: After initiation in clinic, data from the pivotal and crossover studies suggest that the safety profile of SL-APO home dose optimization is comparable to clinic dose optimization.