Motor Fluctuations

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Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials

By Anthony E. Lang MD, FRCPC,*, Ramon L. Rodriguez MD, James T. Boyd MD, Sylvain Chouinard MD, FRCPC, Cindy Zadikoff MD, Alberto J. Espay MD, John T. Slevin MD, MBA, Hubert H. Fernandez MD, Mark F. Lew MD, David A. Stein MD, Per Odin MD, PhD, Victor S.C. Fung MBBS, PhD, FRACP, Fabian Klostermann MD, PhD, Alfonso Fasano MD, PhD, Peter V. Draganov MD, Nathan Schmulewitz MD, Weining Z. Robieson PhD, Susan Eaton PharmD, Krai Chatamra PhD, Janet A. Benesh BSMT and Jordan Dubow MD

ABSTRACT
Background
Continuous administration of levodopa-carbidopa intestinal gel (carbidopa-levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.

Methods
Safety data from 4 studies were summarized using 2 overlapping data sets, permitting the separation of procedure/device–associated (n = 395) from non-procedure/device adverse events (n = 412).

Results
At the data cutoff, median exposure to levodopa-carbidopa intestinal gel was 911 days (range, 1-1980 days) with 963 total patient-years of exposure. Procedure/device adverse events occurred in 300 patients (76%), and serious adverse events occurred in 68 (17%); most frequently reported procedure/device adverse events and serious adverse events were complications of device insertion (41% and 8%, respectively) and abdominal pain (36% and 4%, respectively). Non-procedure/device adverse events occurred in 92% (379), with most frequently reported being insomnia (23%) and falls (23%); 42% (171) had non-procedure/device serious adverse events, with most frequently reported being pneumonia (5%) and PD symptoms (2%). Adverse events led to discontinuation in 17% (72), most frequently because of complication of device insertion (2.4%). There were 34 treatment-emergent deaths (8.3%) in the overlapping data sets, 2 of which (0.5%) were considered “possibly related” to the treatment system.

Conclusion
In the largest collection of levodopa-carbidopa intestinal gel safety data from prospective clinical studies, procedure/device events were frequently reported and occasionally life threatening. Most non-procedure/device events were typical for levodopa treatment and an elderly population. These factors combined with high treatment efficacy led to a relatively low discontinuation rate in advanced PD patients. © 2015 International Parkinson and Movement Disorder Society

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