The efficacy and safety of ropinirole prolonged release tablets as adjunctive therapy in Chinese subjects with advanced Parkinson's disease: A multicenter,double-blind,randomized, placebo-controlled study

AimThe first evaluation of the efficacy and safety of ropinirole prolonged release (PR) as an adjunct to L-dopa in Chinese patients with advanced Parkinson's disease (PD) not optimally controlled with L-dopa.MethodsIn a 24-week, double-blind, placebo-controlled, parallel-group study, subjects with advanced PD were randomized 1:1 to ropinirole PR (N = 175) or placebo (N = 170) as add-on therapy to L-dopa. Primary outcome measure was change from baseline in awake time spent “off”. Starting dose of ropinirole PR was 2 mg/day, titrated based on clinical response (maximum 24 mg/day).ResultsAt week 24, the mean dose of ropinirole PR was 11.4 mg/day with a mean reduction of L-dopa from 506.6 to 411.6 mg/day. Subjects receiving ropinirole PR experienced a significant reduction of “off” time (2.1 h) compared with placebo (0.4 h). Secondary outcome measures including hours of “on” time without troublesome dyskinesis were significantly increased in the ropinirole PR group (1.7 h) compared with placebo (0.3 h). Subjects classified as responders were significantly more frequent in the ropinirole PR (22.8%) than placebo group (2.5%). Efficacy outcomes including Unified Parkinson's disease Rating Scale and PDQ-39 subscales of mobility were significantly improved in the ropinirole PR versus placebo group. The most frequent adverse event experienced in the ropinirole PR group was dyskinesia.ConclusionsThis study demonstrated for the first time in Chinese subjects that ropinirole PR improved Parkinson's disease symptoms, permitting a reduction in L-dopa dose. The adverse events observed were consistent with the established safety profile of ropinirole, with no new safety signal identified.     

Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole.

Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses < or =8 mg/24 h did not show noninferiority to ropinirole at doses < or =24 mg/day. In a post-hoc subgroup analysis, rotigotine < or =8 mg/24 hours had a similar efficacy to ropinirole at doses < or =12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease.     

An open‐label conversion study of pramipexole to ropinirole prolonged release in Parkinson's disease

Ropinirole prolonged release (PR) is a once daily oral dopamine agonist approved for the treatment of Parkinson's disease (PD). The goal of this 4 week, open‐label study was to determine the most effective conversion ratio with the fewest adverse effects (AEs) when switching from pramipexole to ropinirole PR. Sixty patients with PD taking pramipexole were converted overnight to ropinirole PR at ratios of 1:3, 1:4, or 1:5 such that 20 consecutive subjects were enrolled in each group. Ropinirole PR dose adjustments were allowed to maintain efficacy or to reduce AEs. An overnight switch from pramipexole to ropinirole PR was found to be well tolerated and AEs were typical for a dopamine agonist. The most common AEs were worsening of PD symptoms, dizziness, somnolence, and nausea, the majority of which resolved after dose adjustments. Thirteen subjects discontinued ropinirole PR before 4 weeks. These subjects were taking a significantly greater dose of pramipexole, the majority greater than 4 mg/day, and tended to have longer disease durations. A conversion ratio of 1 mg of pramipexole to 4 mg of ropinirole PR resulted in the fewest discontinuations of ropinirole PR, the fewest dose adjustments and the largest percentage of subjects that preferred ropinirole PR. © 2009 Movement Disorder Society     

Rotigotine vs ropinirole in advanced stage Parkinson's disease: A double-blind study

ObjectiveTo confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy.MethodsThis trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period.ResultsThe difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was −6.4 ± 1.2 (95% CI: −8.7 to −4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was −1.4 ± 1.0 (95% CI: −3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted.ConclusionsRotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group.     

A comparison of sumanirole versus placebo or ropinirole for the treatment of patients with early Parkinson's disease.

To assess the safety and efficacy of sumanirole, a highly selective dopamine agonist, versus placebo and demonstrate its noninferiority to ropinirole, 614 patients with early Parkinson's disease (PD) were treated with sumanirole, 1 to 16 mg/day; ropinirole, 0.75 to 24 mg/day; or placebo. Primary end point in this flexible-dose, double-blind, double-dummy, parallel-group study of 40 weeks was the change in total sum of the United Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores from baseline to end of maintenance. Approximately half the subjects in the sumanirole and placebo groups withdrew early from the study, most (51.8% and 68.5%, respectively) due to lack of efficacy. Of the ropinirole subjects who withdrew (50.5%), most discontinued because of adverse events. In sumanirole and ropinirole groups, mean changes from baseline of -2.48 and -5.20 in UPDRS II + III mean scores were significant versus 0.38 in the placebo group (P 相似文献   

Clinical evaluation of ropinirole controlled-release formulation at 18–24 mg/day in Japanese patients with Parkinson's disease

IntroductionThere has been no clinical data on Japanese patients with Parkinson's disease with which to examine whether motor symptoms improve and to assess the safety profile after the dose of ropinirole was increased in those who had not achieved an optimal response to the ropinirole immediate-release formulation 15 mg/day or the controlled-release (CR) formulation 16 mg/day.MethodsThis was a multicenter, randomized, double-blind study, followed by an open-label, long-term study. Participants were randomized at a ratio of 3:1 to the high-dose ropinirole CR (18–24 mg/day) group or the maintenance ropinirole CR 16 mg/day group.ResultsIn the high-dose ropinirole CR group (N = 61), the Japanese unified Parkinson's disease rating scale Part III total score at week 12 was significantly decreased compared with the baseline total score (−4.8 ± 5.95, [95% CI, −6.3 to −3.2], p < 0.001). However, a comparable decrease was also observed in the maintenance ropinirole CR 16 mg/day group (N = 20) (−5.7 ± 5.18, [95% CI, −8.1 to −3.3]), with no statistically significant difference in the adjusted mean change between the high-dose and maintenance groups (0.5 [95% CI, −2.4 to 3.4]). Plasma drug concentrations increased at doses higher than 16 mg/day, but did not increase significantly in a dose-dependent manner at doses of 18–24 mg/day. No adverse events were found that would affect the known safety profile of ropinirole.ConclusionThis study did not demonstrate the difference in efficacy between the high-dose ropinirole CR group and the maintenance ropinirole CR group.Clinical trial registrationClinicalTrials.gov identifier: NCT01929317.     

Concomitant development of hypersexuality and delusional jealousy in patients with Parkinson's disease: A case series

BackgroundBoth impulse-control disorders and delusional jealousy (DJ) may be considered non-motor side-effects of dopamine agonist therapy in Parkinson's disease (PD). We aimed to investigate the possible concomitant development of these features in PD and their clinical correlates.MethodsWe performed a cross-sectional investigation in 1063 consecutive PD patients with the Questionnaire for Impulsive Compulsive Disorders in Parkinson's disease and the Parkinson's Psychosis Questionnaire.Results81 patients presented ICDs (prevalence 7.61%) and 23 patients presented DJ (17 males, 6 females; prevalence 2.16%). 9 male PD patients presented both DJ and ICDs (39.13% of patients with DJ, 11.11% of patients with ICDs; prevalence of 0.84% in the whole PD sample), with a concomitant onset of delusional jealousy and hypersexuality in 8 cases and a concomitant onset of delusional jealousy and pathological gambling in 2 cases.DiscussionHypersexuality and delusional jealousy may occur independently in PD patients “on” dopamine agonist therapy, but may develop together probably reflecting a common alteration of sexuality (sexual arousal and jealousy) The presence of both of these clinical features and sexuality more in general should be investigated when features of either one of them appear. Further confirmation is needed in larger samples of patients.     

The levodopa dose-sparing capacity of pergolide compared with that of bromocriptine in an open-label,crossover study

The levodopa dose-sparing capacity of pergolide and bromocriptine, along with the maximum ability to improve activity of daily living and motor scores, were compared in 33 patients with idiopathic Parkinson's disease (Hoehn-Yahr stage 2–4) in a 24-week, open-label, crossover study. Patients received one dopamine agonist for 12 weeks and then were crossed over to the other for 12 weeks (8 weeks, titration; 4 weeks, steady state in each period). The maximum doses allowed were pergolide 5 mg/day and bromocriptine 50 mg/day. As patients' clinical response to a dopamine agonist increased, the levodopa dose was decreased. Twenty-seven patients completed the study. No serious adverse events or clinically significant changes in vital signs or laboratory tests were observed. The mean doses of bromocriptine and pergolide at the end of titration were 21.7 ± 5.6 mg (bromocriptine data for the two groups combined) and 3.6 ± 1.1 mg (pergolide data for the two groups combined), respectively. The mean levodopa dose was reduced 83% with bromocriptine as the first agent and increased 28.0% with bromocriptine as the second agent The mean levodopa dose was reduced 31.4% with pergolide as the first agent and 15.5% with pergolide as the second agent Levodopa could not be discontinued in any of the patients. Statistically significant levodopa dose-sparing capacity and considerable clinical benefit were achieved with both agonists; however, the results were more favorable with pergolide.     

Early treatment benefits of ropinirole prolonged release in Parkinson's disease patients with motor fluctuations

We performed a retrospective analysis of the Efficacy And Safety Evaluation in Parkinson's Disease (EASE‐PD) Adjunct Study, assessing the minimum time to symptom improvement after initiation of ropinirole prolonged release (2–24 mg/day) versus placebo in patients with moderate‐to‐advanced PD not optimally controlled with levodopa. Ropinirole prolonged release was superior to placebo at Week 2 for change from baseline in “off” time (adjusted mean treatment difference [AMTD] – 0.7 hours; 95% confidence interval [CI], –1.1, –0.2; P = 0.0029), and “on” time without troublesome dyskinesia (0.4 hours; 95%CI, 0.01, 0.88; P = 0.0444). At Week 4, improvements were seen in change from baseline in Unified Parkinson's Disease Rating Scale total motor score (AMTD, –3.1; 95%CI, –4.4, –1.8; P < 0.0001), activities of daily living score (AMTD, –1.1; 95%CI, –1.7, –0.5; P = 0.0004), and the cardinal symptoms of PD compared with placebo. These analyses indicate that once‐daily, adjunctive ropinirole prolonged release can offer PD symptom control 2 weeks after treatment initiation. © 2010 Movement Disorder Society     

Onset of dyskinesia with adjunct ropinirole prolonged‐release or additional levodopa in early Parkinson's disease

Levodopa‐induced dyskinesia can result in significant functional disability and reduced quality of life in patients with Parkinson's disease (PD). The goal of this study was to determine if the addition of once‐daily ropinirole 24‐hour prolonged‐release (n = 104) in PD patients not optimally controlled with levodopa after up to 3 years of therapy with less than 600 mg/d delays the onset of dyskinesia compared with increasing doses of levodopa (n = 104). During the study, 3% of the ropinirole prolonged‐release group (mean dose 10 mg/d) and 17% of the levodopa group (mean additional dose 284 mg/d) developed dyskinesia (P < 0.001). There were no significant differences in change in Unified Parkinson's Disease Rating Scale activities of daily living or motor scores, suggesting comparable efficacy between the two treatments. Adverse events were comparable in the two groups with nausea, dizziness, insomnia, back pain, arthralgia, somnolence, fatigue, and pain most commonly reported. Ropinirole prolonged‐release delayed the onset of dyskinesia with comparable efficacy to increased doses of levodopa in early PD patients not optimally controlled with levodopa. © 2010 Movement Disorder Society     

Efficacy and safety of atypical antipsychotics for psychosis in Parkinson's disease: A systematic review and Bayesian network meta-analysis

IntroductionWe performed a systematic review and Bayesian network meta-analysis to clarify the relative efficacy and safety of pimavanserin compared to atypical antipsychotics for psychosis in Parkinson's disease (PD).MethodsPubMed, Embase, Cochrane Central Register of Controlled Trials, and Japana Centra Revuo Medicina Web were searched for relevant articles until October 31, 2019. Eligible randomized controlled trials were synthesized for efficacy (Brief Psychiatry Rating Scale [BPRS] and Clinical Global Impression Scale [CGI-S]) and safety (Unified Parkinson's Disease Rating Scale part III [UPDRS-III] and dropouts due to adverse events). The mean differences (BPRS, CGI-S, and UPDRS-III) or odds ratios (dropouts due to adverse events) between each active drug and placebo were estimated and summarized as means and 95% credible intervals, respectively.ResultsWe identified 17 relevant trials. Clozapine showed significant efficacy (BPRS, −5.6 [−8.4 to −2.7] and CGI-S, −1.2 [−1.7 to −0.7]), with low impact on motor functions (UPDRS-III, −1.1 [−3.8 to 1.5]), but an increase in dropouts due to adverse events (2.9 [0.9 to 9.6]) as compared to placebo. Pimavanserin also showed significant efficacy (CGI-S, −0.5 [−0.9 to −0.2]) and similar impact on motor functions (UPDRS-III, 0.2 [−1.4 to 1.9]), but a tendency of increase in dropouts due to adverse events (2.2 [0.5 to 12.4]) as compared to placebo.ConclusionsClozapine showed an efficacy with low impact on motor functions that was consistent with previous reports. Although the efficacy of pimavanserin may be inferior to that of clozapine, it had a favorable profile for the treatment of psychosis in PD.     

A long-term follow-up of safety and clinical efficacy of NTCELL® [Immunoprotected (Alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease

IntroductionIn 2019, we published the results of a Phase IIb randomized controlled trial of putaminal encapsulated porcine choroid plexus cell (termed NTCELL®) administration in patients with Parkinson's disease. This study failed to meet its primary efficacy end-point of a change in UPDRS part III score in the ‘off’ state at 26-weeks post-implant. However, a number of secondary end-points reached statistical significance. We questioned whether with longer follow-up, clinically significant improvements would be observed. For this reason, we decided to follow-up all patients periodically to week 104. Herein, we report the results of this long-term follow-up.MethodsAll 18 patients included in the original study were periodically re-assessed at weeks 52, 78 and 104 post-implant. At each time-point, motor and non-motor function, quality of life and levodopa equivalent daily dose was assessed using a standardized testing battery.ResultsAt week 104, no significant differences in UPDRS part III scores in the ‘off’ state were observed in any of the treatment groups compared to baseline. Only a single serious adverse event - hospitalisation due to Parkinson's disease rigidity not responding to changes in medications – was considered potentially related to the implant procedure. There was no evidence of xenogeneic viral transmission.ConclusionUn-blinded, long-duration follow-up to week 104 post-implantation showed no evidence that putaminal NTCELL® administration produces significant clinical benefit in patients with moderately advanced Parkinson's disease.     

A six-month multicentre,double-blind,bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by <Emphasis Type="SmallCaps">l</Emphasis>-dopa

Summary. Objectives: To compare the safety and efficacy of ropinirole and bromocriptine as adjunct therapy in patients with Parkinson's disease (PD) not optimally controlled by L-dopa. Methods: A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the level of daily dosage of L-dopa, presence of motor fluctuations, and use of dopamine agonist before study entry. Patient response was defined as at least a 20% reduction in daily L-dopa dose plus: for patients with no prior treatment and no motor fluctuations, a 20% reduction in UPDRS motor score; for patients with motor fluctuations, a 20% reduction in time spent "off"; and for patients already taking an agonist, an improvement on the CGI scale. Results: Safety assessments showed no significant differences in the two treatment groups for patients without prior dopamine-agonist therapy. In the group of patients with prior dopamine-agonist therapy, more patients reported adverse events in the ropinirole group (90% versus 79%, p < 0.001). The proportions of responders tended to be higher in ropinirole groups compared with bromocriptine groups and, in the subgroup with motor fluc-tuations, this difference was statistically significant (9.1% versus 0.0%, respectively; p < 0.05). Conclusions: Both drugs were well tolerated. In patients receiving a relatively high dose of L-dopa and requiring the addition of a dopamine agonist to control motor fluctuations or dyskinesias, ropinirole was significantly more effective than bromocriptine. Received January 31, 2001; accepted October 23, 2001     

Phase II safety,tolerability, and dose selection study of isradipine as a potential disease‐modifying intervention in early Parkinson's disease (STEADY‐PD)

Isradipine, a dihydropyridine calcium channel antagonist, has been shown to be neuroprotective in animal models of Parkinson's disease (PD). To establish a dosage of isradipine controlled‐release (CR) that is tolerable and demonstrates preliminary efficacy for use in a future pivotal efficacy trial a Phase 2, randomized, double‐blind, parallel group trial (Safety, Tolerability and Efficacy Assessment of Dynacirc CR in Parkinson Disease [STEADY‐PD]) was undertaken in subjects with early PD not requiring dopaminergic therapy (dopamine agonists or levodopa) randomized 1:1:1:1 to 5, 10, or 20 mg of isradipine CR or matching placebo daily. The primary outcome was tolerability defined as no more than a 30% difference in the proportion of patients completing the study on the originally assigned dosage between an active and placebo group. If more than one isradipine dosage was tolerable, then a 3‐point difference in total Unified Parkinson's Disease Rating Scale (UPDRS) change between baseline and week 52 (or time to sufficient disability to require dopaminergic therapy) was taken as a criterion for selection of the most desirable dosage for future study. STEADY‐PD enrolled 99 subjects. The tolerability of isradipine was dose dependent: placebo, 25 of 26 patients (96%); 5 mg, 19 of 23 patients (83%); 10 mg 19 of 26 patients (73%); and 20 mg 9 of 24 patients (37%). There was no difference in change in UPDRS among dosages. The most common adverse events were peripheral edema (30) and dizziness (24). Isradipine 10 mg daily was the maximal tolerable dosage in this study of early PD. A large placebo‐controlled trial will be necessary and is planned to assess efficacy of isradipine 10 mg daily to slow progression of PD disability. © 2013 International Parkinson and Movement Disorder Society.     

Variations in hospitalization rates across Parkinson's Foundation Centers of Excellence

IntroductionPatients with Parkinson's disease (PD) are at increased risk for hospitalization and often experience worsening of PD when hospitalized. It is therefore important to identify strategies to prevent hospitalization.MethodsHospital encounter rates in different Parkinson's Foundation Centers of Excellence in United States, Canada, Israel and the Netherlands were analyzed as part of the Parkinson Foundation Parkinson's Outcomes Project (PF-POP). Multivariate logistic regression was used to estimate the odds ratio for hospitalization, adjusted for risk factors.ResultsBaseline age, disease duration, other relative than spouse/partner as care giver, cancer, arthritis, other comorbidities, falls, use of levodopa, use of dopamine agonist, use of COMT inhibitor, occupational therapy before the baseline visit, PDQ-39, MSCI total score and time between visits were significantly associated with the risk of hospital encounters. After adjustment for these factors, two centers had significantly lower odds for hospitalization admission and ER visit (minimum OR 0.3) and four centers had significantly higher odds (maximum OR 1.5) than the average center. Four centers had significantly lower hazard ratios for time to re-hospitalization compared to the average center. Reducing hospital admission rates in those centers with higher than average rates would reduce overall hospitalizations by 11%. Applied to PD patients over 65 nationwide this represents a potential for cost savings of greater than $1 billion over 48 months.ConclusionEncounter rates vary even across expert centers and suggest that practices carried out in some centers may reduce the risk of hospitalization. Further research will be necessary to identify these practices and implement them more widely to improve care for people with PD.     

Sumanirole versus placebo or ropinirole for the adjunctive treatment of patients with advanced Parkinson's disease.

The aims of this study were to assess the safety, tolerability, and efficacy of sumanirole, a highly selective D(2) dopamine receptor agonist, versus placebo in subjects with advanced Parkinson's disease (PD), and to demonstrate noninferiority of sumanirole to ropinirole. In this flexible-dose, randomized, double-blind, double-dummy, parallel-group study, 948 subjects were treated with sumanirole 1 to 48 mg/day, ropinirole 0.75 to 24 mg/day, or placebo. Treatment consisted of 13 weeks of dose escalation, 26 weeks of maintenance, and 1 week of tapering. Approximately 70% of subjects treated with either sumanirole or ropinirole completed the study. Statistical significance (P < 0.0001) was achieved when both sumanirole and ropinirole groups were compared with placebo, with mean differences of -7.7 and -8.8 on combined sum of the Unified Parkinson's Disease Rating Scale (UPDRS) part II (average on and off) and part III total scores at the end of maintenance. Noninferiority of sumanirole to ropinirole was also demonstrated, with a sumanirole minus ropinirole difference of 1.17 (90% CI: -0.56 to 2.89). Both dopamine agonists, sumanirole and ropinirole, were statistically superior compared with placebo as adjunctive therapy for patients with advanced Parkinson's disease, based on UPDRS II + III total score. Noninferiority of sumanirole to ropinirole was established, with comparable tolerability profiles.     

Randomized trial of IPX066, carbidopa/levodopa extended release,in early Parkinson's disease

ObjectiveIPX066 is an extended release carbidopa/levodopa formulation designed to rapidly attain and maintain therapeutic plasma concentrations for a prolonged duration, allowing dosing intervals of approximately 6 h. The objective was to assess the efficacy, safety, and impact on quality of life of IPX066 in the treatment of levodopa-naive Parkinson's disease (PD) patients.MethodsThis was a randomized, double-blind, placebo-controlled, 30-week study of 381 levodopa-naïve patients assigned to placebo or IPX066 containing 145, 245 or 390 mg of levodopa administered three times daily (TID). The primary efficacy measure was change from Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (Part II) + motor scores (Part III), at 30 weeks. Secondary outcome measures included UPDRS total and subscores, patient and clinician global impressions (PGI-I, CGI-I), and the Parkinson's Disease Questionnaire (PDQ-39).ResultsAll IPX066 dosages were superior to placebo throughout the study and at 30 weeks (P < 0.0001). The mean improvement in UPDRS Parts II + III at 30 weeks compared to baseline was 11.7, 12.9, and 14.9 points for the three dosages and 0.6 points for placebo (P < 0.0001, all dosages). PDQ-39 total scores improved with IPX066 (P ≤ 0.034, all dosages). The most commonly reported adverse events with IPX066 included nausea, dizziness, and headache. No unexpected drug-related serious adverse events were reported.ConclusionIPX066 provided significant clinical benefits at the three dosages tested compared to placebo and was well tolerated in levodopa-naive PD patients. Of the dosages tested, IPX066 145 mg TID appeared to provide the best overall balance between efficacy and safety.     

Dopa-decarboxylase gene polymorphisms affect the motor response to l-dopa in Parkinson's disease

BackgroundIn Parkinson's disease (PD), the response to l-dopa is highly variable and unpredictable. The major pathway for dopamine synthesis from l-dopa is decarboxylation by aromatic l-amino acid decarboxylase (AAAD, encoded by the DDC gene).ObjectiveTo determine the motor response to l-dopa in PD patients as a function of the DDC gene promoter polymorphisms (rs921451 T > C polymorphism (DDC^T/C) and rs3837091 AGAG del (DDC^AGAG/−)).MethodsThirty-three Caucasian PD patients underwent an acute l-dopa challenge together with the peripheral AAAD inhibitor benserazide and were genotyped for rs921451 and rs3837091. The primary efficacy criterion was the motor response to l-dopa, as estimated by the area under the curve for the change in the Unified Parkinson's Disease Rating Scale part III (UPDRS) score relative to baseline (AUC_ΔUPDRS) in the 4 h following l-dopa administration. Secondary endpoints were pharmacokinetic parameters for plasma levels of l-dopa and dopamine. Investigators and patients were blinded to genotypes data throughout the study.ResultsWhen adjusted for the l-dopa dose, the AUC_ΔUPDRS was significantly lower in DDC^CC/CT patients (n = 14) than in DDC^TT patients (n = 19) and significantly lower in DDC^{−/− or AGAG/−} patients (n = 8) than in DDC^AGAG/AGAG patients (n = 25). There were no significant intergroup differences in plasma pharmacokinetic parameters for l-dopa and dopamine.DiscussionThe rs921451 and rs3837091 polymorphisms of the DDC gene promoter influence the motor response to l-dopa but do not significantly change peripheral pharmacokinetic parameters for l-dopa and dopamine. Our results suggest that DDC may be a genetic modifier of the l-dopa response in Parkinson's disease.     

Efficacy and safety of non-ergot dopamine-receptor agonists as an adjunct to levodopa in advanced Parkinson's disease: A network meta-analysis

Background and purpose

Non-ergot dopamine agonists (NEDAs) have been used as an adjunct therapy to levodopa in advanced Parkinson's disease (PD) for many years. However, there is no strong evidence that a given NEDA is more potent than another. To compare and rank the efficacy, tolerability, and safety of six commonly used NEDAs as an adjunct to levodopa in advanced PD, which includes long-acting and standard formulations, a network meta-analysis was performed.

Methods

The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang databases were searched from January 1996 to June 2022 for eligible randomized controlled trials (RCTs). Six NEDAs, including rotigotine transdermal patch, ropinirole immediate-release (IR)/prolonged-release (PR), pramipexole IR/extended-release (ER), and piribedil, were investigated.

Results

A total of 34 RCTs (7868 patients) were included in the current study. The surface under the cumulative ranking curve indicated that ropinirole PR was associated with the best improvement in Unified Parkinson's Disease Rating Scale (UPDRS)-II, UPDRS-III, and UPDRS-II + III (0.811, 0.742, and 0.827). For OFF time reduction, pramipexole IR ranked first (0.979), and ropinirole PR ranked first in OFF time responder rate (0.927). Pramipexole ER ranked first in overall withdrawals, and rotigotine transdermal patch ranked first in the incidence of adverse events (≥1 AEs).

Conclusions

This network meta-analysis suggests six commonly used NEDAs are effective as an adjunct to levodopa in advanced PD. In comprehensive consideration of better symptomatic management, ropinirole PR may be a better choice than other NEDAs in advanced PD. Six NEDAs showed different profiles of AEs.     

Past smoking and current dopamine agonist use show an independent and dose-dependent association with impulse control disorders in Parkinson's disease

BackgroundPrevious studies have described the association between dopamine replacement therapy in Parkinson's disease and impulse control disorders.MethodsA case–control study was performed to establish the prevalence of four of these behaviors in Brazilian patients with Parkinson's disease on stable dopamine replacement therapy and the possible associated risk factors. We investigated 152 patients and 212 healthy controls for pathological gambling, compulsive sexual behavior and compulsive buying and eating.ResultsOverall, patients had more impulsive control disorders than controls (18.4% vs. 4.2%, P < 0.001). Impulse control disorders were more common in younger patients (P = 0.008) and in those taking dopamine agonist (P < 0.001) and levodopa (P = 0.02). Higher Unified Parkinson's Disease Rating Scale motor score (P = 0.03) and past smoking (P = 0.02) were also associated in the univariate analysis. Variables independently associated with impulse control disorders were history of smoking (odds ratio = 1.059 for each year of smoking, P = 0.010) and current use of pramipexole (odds ratio = 2.551 for each increase in 1 mg, P < 0.001).ConclusionsDopaminergic stimulation and previous exposure to smoking are independently associated with impulse control disorders in a dose-dependent manner.