Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials
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 medicat...
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| Published in: | Movement disorders Vol. 31; no. 4; pp. 538 - 546 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Blackwell Publishing Ltd
01.04.2016
Wiley Subscription Services, Inc John Wiley and Sons Inc |
| Subjects: | |
| ISSN: | 0885-3185, 1531-8257, 1531-8257 |
| Online Access: | Get full text |
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| Summary: | 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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| Bibliography: | ArticleID:MDS26485 AbbVie Inc - No. NCT00357994/NCT00660387; No. NCT00335153; No. NCT00660673; No. NCT00360568 ark:/67375/WNG-BW56QHBP-H istex:8667B03680EF1A8050AC81E7CEFCE44E6D508A56 AbbVie Inc. funded these studies. AbbVie Inc. participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. Relevant conflicts of interests/financial disclosures Funding agencies A.E.L. has received compensation from AbbVie Inc. for participating in scientific advisory boards. R.L.R. was a study investigator and has received compensation from AbbVie Inc. for research and scientific advisory services. J.T.B., S.C., C.Z., M.F.L., and A.J.E. were study investigators and have received compensation from AbbVie Inc. for serving as a consultant, lecturer, and/or participating in scientific advisory boards. J.T.S. and F.K. were study investigators and have received compensation from AbbVie Inc. for participating in scientific advisory boards. H.H.F. was a study investigator and has served as a consultant for AbbVie Inc. through a contract between AbbVie Inc. and Cleveland Clinic Foundation; he has not received personal compensation from AbbVie Inc. D.A.S. was a medical monitor for the studies through a contract with his employer, Quintiles, and AbbVie Inc. P.O. was a study investigator in AbbVie Inc.–sponsored studies and has received compensation from AbbVie Inc. for serving as a consultant and lecturer. V.S.C.F. was a study investigator and has also received compensation from AbbVie Inc. for participating in scientific advisory boards; AbbVie Inc. contributed to funding for a Parkinson's disease nurse specialist in the form of an unrestricted grant to his institution. A.F. received compensation from AbbVie Inc. for serving as a lecturer and participating in scientific advisory boards. P.V.D. has received compensation from AbbVie Inc. for serving as a consultant, scientific adviser, and lecturer. N.S. has received compensation from AbbVie Inc. for serving as a consultant, scientific adviser and lecturer. J.D. is a former employee of AbbVie Inc. W.Z.R., S.E., K.C., and J.A.B. are employees of AbbVie Inc. and hold stock or stock options. This article was published online on 23 December 2015. After online publication, updates were made to the text. This notice is included in the online and print versions to indicate that both have been corrected on 04 January 2016. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Relevant conflicts of interests/financial disclosures: A.E.L. has received compensation from AbbVie Inc. for participating in scientific advisory boards. R.L.R. was a study investigator and has received compensation from AbbVie Inc. for research and scientific advisory services. J.T.B., S.C., C.Z., M.F.L., and A.J.E. were study investigators and have received compensation from AbbVie Inc. for serving as a consultant, lecturer, and/or participating in scientific advisory boards. J.T.S. and F.K. were study investigators and have received compensation from AbbVie Inc. for participating in scientific advisory boards. H.H.F. was a study investigator and has served as a consultant for AbbVie Inc. through a contract between AbbVie Inc. and Cleveland Clinic Foundation; he has not received personal compensation from AbbVie Inc. D.A.S. was a medical monitor for the studies through a contract with his employer, Quintiles, and AbbVie Inc. P.O. was a study investigator in AbbVie Inc.–sponsored studies and has received compensation from AbbVie Inc. for serving as a consultant and lecturer. V.S.C.F. was a study investigator and has also received compensation from AbbVie Inc. for participating in scientific advisory boards; AbbVie Inc. contributed to funding for a Parkinson's disease nurse specialist in the form of an unrestricted grant to his institution. A.F. received compensation from AbbVie Inc. for serving as a lecturer and participating in scientific advisory boards. P.V.D. has received compensation from AbbVie Inc. for serving as a consultant, scientific adviser, and lecturer. N.S. has received compensation from AbbVie Inc. for serving as a consultant, scientific adviser and lecturer. J.D. is a former employee of AbbVie Inc. W.Z.R., S.E., K.C., and J.A.B. are employees of AbbVie Inc. and hold stock or stock options. Funding agencies: AbbVie Inc. funded these studies. AbbVie Inc. participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. |
| ISSN: | 0885-3185 1531-8257 1531-8257 |
| DOI: | 10.1002/mds.26485 |