PMID- 25895021
OWN - NLM
STAT- MEDLINE
DCOM- 20160613
LR  - 20220316
IS  - 1179-1934 (Electronic)
IS  - 1172-7047 (Print)
IS  - 1172-7047 (Linking)
VI  - 29
IP  - 4
DP  - 2015 Apr
TI  - Long-Term Treatment with Extended-Release Carbidopa-Levodopa (IPX066) in Early 
      and Advanced Parkinson's Disease: A 9-Month Open-Label Extension Trial.
PG  - 341-50
LID - 10.1007/s40263-015-0242-2 [doi]
AB  - BACKGROUND AND OBJECTIVE: IPX066 is a multiparticulate extended-release 
      formulation of carbidopa-levodopa, designed to produce prolonged therapeutic 
      levodopa plasma concentrations. This 9-month open-label extension study assessed 
      its long-term safety and clinical utility in early and advanced Parkinson's 
      disease (PD). METHODS: Participants were enrolled from two phase III IPX066 
      studies and one open-label phase II study. Early PD patients were titrated to an 
      appropriate dosing regimen while advanced patients started with regimens 
      established in the antecedent studies. Adjustment was allowed throughout the 
      extension. Clinical utility measures included the Unified Parkinson's Disease 
      Rating Scale (UPDRS) and Patient Global Impression (PGI) ratings. RESULTS: Among 
      268 early PD patients, 53.4 % reported adverse events (AEs) and 1.1 % (three 
      patients) discontinued due to AEs; the most frequent AEs were nausea (5.6 %) and 
      insomnia (5.6 %). Among 349 advanced patients, 60.2 % reported AEs and 3.7 % (13 
      patients) discontinued due to AEs; the most frequent AEs were dyskinesia (6.9 %) 
      and fall (6.6 %). At month 9 (or early termination), 78.3 % of early patients 
      were taking IPX066 three times daily (median: 720 mg/day) and 87.7 % of advanced 
      patients were taking IPX066 three or four times daily (median: 1450 mg/day). 
      Adjusting for 70 % bioavailability relative to immediate-release (IR) 
      carbidopa-levodopa, the median dosages correspond to ~500 and ~1015 mg/day of IR 
      levodopa in early and advanced PD, respectively. Based on the plasma profiles 
      previously observed in PD patients, the IPX066 regimens in the extension can be 
      estimated to provide a levodopa Cmax (maximum plasma drug concentration) similar 
      to or lower than that provided by IR regimens during the antecedent trials. UPDRS 
      and PGI findings showed sustained treatment effects throughout the extension. 
      CONCLUSION: During 9 months of extended use, IPX066 exhibited a 
      safety/tolerability profile consistent with dopaminergic PD therapy.
FAU - Waters, Cheryl H
AU  - Waters CH
AD  - Columbia University Medical Center, New York, NY, USA, cw345@columbia.edu.
FAU - Nausieda, Paul
AU  - Nausieda P
FAU - Dzyak, Lyudmila
AU  - Dzyak L
FAU - Spiegel, Joerg
AU  - Spiegel J
FAU - Rudzinska, Monika
AU  - Rudzinska M
FAU - Silver, Dee E
AU  - Silver DE
FAU - Tsurkalenko, Elena S
AU  - Tsurkalenko ES
FAU - Kell, Sherron
AU  - Kell S
FAU - Hsu, Ann
AU  - Hsu A
FAU - Khanna, Sarita
AU  - Khanna S
FAU - Gupta, Suneel
AU  - Gupta S
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - CNS Drugs
JT  - CNS drugs
JID - 9431220
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Combinations)
RN  - 0 (carbidopa, levodopa drug combination)
RN  - 46627O600J (Levodopa)
RN  - MNX7R8C5VO (Carbidopa)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antiparkinson Agents/*administration & dosage/adverse effects/blood
MH  - Carbidopa/*administration & dosage/adverse effects/blood
MH  - Cross-Over Studies
MH  - Delayed-Action Preparations/administration & dosage/adverse effects/metabolism
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Female
MH  - Humans
MH  - Levodopa/*administration & dosage/adverse effects/blood
MH  - Long-Term Care
MH  - Male
MH  - Middle Aged
MH  - Parkinson Disease/blood/*drug therapy/epidemiology
MH  - Severity of Illness Index
PMC - PMC4555339
EDAT- 2015/04/22 06:00
MHDA- 2016/06/14 06:00
PMCR- 2015/04/17
CRDT- 2015/04/21 06:00
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/06/14 06:00 [medline]
PHST- 2015/04/17 00:00 [pmc-release]
AID - 242 [pii]
AID - 10.1007/s40263-015-0242-2 [doi]
PST - ppublish
SO  - CNS Drugs. 2015 Apr;29(4):341-50. doi: 10.1007/s40263-015-0242-2.