Levodopa-carbidopa enteral suspension in advanced Parkinson’s disease: clinical evidence and experience

The duration of action of oral levodopa becomes shorter as Parkinson’s disease (PD) progresses. Patients with advanced PD may develop potentially disabling motor fluctuations and abnormal involuntary movement (dyskinesia), which cannot be managed with optimized oral or transdermal PD medications. The progressively worsening symptoms can have a substantial impact on the patient quality of life (QoL). Levodopa–carbidopa intestinal gel (LCIG) is delivered continuously via a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). LCIG is licensed for the treatment of levodopa-responsive advanced PD in individuals experiencing severe motor fluctuations and dyskinesia when available combinations of antiparkinsonian medications have not given satisfactory results. Initial evidence for the efficacy and tolerability of LCIG came from a number of small-scale studies, but recently, three prospective studies have provided higher quality evidence. A 12-week double-blind comparison of LCIG with standard levodopa therapy, a 52-week open-label study extension of the double-blind study, and a 54-week open-label safety study, demonstrated significant improvements in ‘off’ time and ‘on’ time without troublesome dyskinesia, and QoL measures that were maintained in the longer term. There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS) although the evidence is limited. There is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL. This review surveys the clinical evidence for the effectiveness and tolerability of LCIG in the management of advanced PD and highlights some practical considerations to help optimize treatment.

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Adjunct rasagiline to treat Parkinson’s disease with motor fluctuations: a randomized, double-blind study in China

Translational Neurodegeneration ◽

10.1186/s40035-018-0119-7 ◽

2018 ◽

Vol 7 (1) ◽

Cited By ~ 6

Author(s):

Zhenxin Zhang ◽

Ming Shao ◽

Shengdi Chen ◽

Chunfeng Liu ◽

Rong Peng ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Fluctuations ◽

Blind Study ◽

Double Blind Study ◽

Double Blind

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Long-term safety and efficacy of opicapone in Japanese Parkinson’s patients with motor fluctuations

Journal of Neural Transmission ◽

10.1007/s00702-021-02315-1 ◽

2021 ◽

Author(s):

Atsushi Takeda ◽

Ryosuke Takahashi ◽

Yoshio Tsuboi ◽

Masahiro Nomoto ◽

Tetsuya Maeda ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Adverse Events ◽

Motor Fluctuations ◽

Open Label ◽

Double Blind ◽

Safety And Efficacy ◽

Open Label Extension ◽

Off Time

AbstractThe double-blind part of the COMFORT-PD (COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson’s Disease) study in Japanese levodopa-treated patients with Parkinson’s disease and motor fluctuations found that both opicapone 25 and 50 mg were significantly more effective than placebo. This 52-week open-label extension study evaluated the long-term safety and efficacy of opicapone 50 mg tablets in patients who completed the double-blind part of the COMFORT-PD study. Safety was monitored via adverse events, laboratory testing, and physical, cardiovascular and neurological examinations. Efficacy was primarily assessed by change in OFF-time. Secondary efficacy measures included: ON-time, percentage of OFF/ON-time responders, other outcomes from the double-blind part. 391/437 patients were transferred to the open-label extension period and included in the safety analysis set (full analysis set, n = 387; open-label completers, n = 316). Adverse events were frequently reported (n = 338, 86.4%), but < 50% were considered drug-related (39.9%) and few were considered serious (2.6%) or led to discontinuation (2.8%). Decreased OFF-time was consistently observed over the open-label period regardless of initial randomization. Change [LSM (SE)] in OFF-time from the open-label baseline to the last visit showed a persistent effect in patients initially randomized to opicapone 25 mg [− 0.37 (0.20) h, P = 0.0689] and opicapone 50 mg [− 0.07 (0.21) h, P = 0.6913] whereas opicapone 50 mg led to a statistically significant reduction in the previous placebo group [− 1.26 (0.19) h, P < 0.05]. Once-daily opicapone 50 mg was generally well tolerated and consistently reduced OFF-time over 52 weeks in Japanese levodopa-treated patients with motor fluctuations.Trial registration JapicCTI-153112; date of registration: December 25, 2015.

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Faculty Opinions recommendation of Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717995409.793474520 ◽

2013 ◽

Author(s):

Cynthia Comella

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Extended Release ◽

Immediate Release ◽

Motor Fluctuations ◽

Double Blind Trial ◽

Phase 3 ◽

Double Blind ◽

Blind Trial

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Lamotrigine in Parkinson's disease — a double blind study

Journal of Neural Transmission - Parkinsons Disease and Dementia Section ◽

10.1007/bf02251231 ◽

1995 ◽

Vol 10 (2-3) ◽

pp. 199-206 ◽

Cited By ~ 13

Author(s):

F. Zipp ◽

F. Bürklin ◽

K. Stecker ◽

H. Baas ◽

P. -A. Fischer

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Blind Study ◽

Double Blind Study ◽

Double Blind

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Foetal Cell Transplantation for Parkinson’s Disease: Focus on Graft-Induced Dyskinesia

Parkinson s Disease ◽

10.1155/2015/563820 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Elisabetta Tronci ◽

Camino Fidalgo ◽

Manolo Carta

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Transplantation ◽

Open Label ◽

Double Blind ◽

Clinical Investigations ◽

Serotonin Neurons ◽

Ventral Mesencephalic ◽

Preclinical And Clinical Studies ◽

Foetal Cell

Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson’s disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID.

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