PMID- 25847690
OWN - NLM
STAT- MEDLINE
DCOM- 20160608
LR  - 20150917
IS  - 1531-8257 (Electronic)
IS  - 0885-3185 (Linking)
VI  - 30
IP  - 9
DP  - 2015 Aug
TI  - Gastroretentive carbidopa/levodopa, DM-1992, for the treatment of advanced 
      Parkinson's disease.
PG  - 1222-8
LID - 10.1002/mds.26219 [doi]
AB  - OBJECTIVES: This study was undertaken to compare efficacy, tolerability, and 
      pharmacokinetics of DM-1992, an extended-release formulation of 
      carbidopa/levodopa (CD/L-dopa) with immediate-release (IR) CD/L-dopa in patients 
      with advanced Parkinson's disease. METHODS: This randomized, open-label, 
      crossover study included a 3-d baseline and two 10-d treatment periods. Patients 
      with daily OFF time of 2.5 h or more taking 400 mg or more L-dopa/d in four or 
      more divided doses were titrated to stable regimens of DM-1992 2 times per day or 
      CD/L-dopa IR 3 times to 8 times per day. Patients were allowed to take rescue 
      CD/L-dopa as needed. Using home diaries, patients recorded OFF time and ON time 
      with or without troublesome dyskinesia during baseline and treatment days 7 
      through 9. During 12-h clinic visits on day 10, plasma samples were collected for 
      pharmacokinetics, and motor performance was assessed hourly. RESULTS: Thirty-four 
      patients were enrolled; mean baseline L-dopa dosage was 968 mg/d. After 
      titration, CD/L-dopa IR was dosed 4.8 times per day and DM-1992, 2 times per day. 
      Rescue CD/L-dopa IR was given 1.3 times during the DM-1992 arm and 0.2 times 
      during the CD/L-dopa IR arm. The reduction from baseline in % OFF time was 
      greater for DM-1992 compared with CD/L-dopa IR (-5.52% vs. +1.33%; P = 0.0471). 
      At steady-state, compared with CD/L-dopa IR, DM-1992 exhibited a smoother plasma 
      L-dopa concentration profile mostly because of a significantly higher (day 10) 
      predose L-dopa concentration, associated with enhanced motor performance. 
      Although more patients taking DM-1992 had one or more adverse events (AEs) than 
      CD/L-dopa IR patients (35% vs. 15%), no pattern to the AEs was seen, nor any 
      resulting discontinuations. CONCLUSIONS: DM-1992 was associated with a reduction 
      in %OFF time compared with CD/L-dopa IR despite a reduced dosing frequency. 
      Although the open-label study design and the greater number of rescue doses 
      during the DM-1992 arm call for caution in interpreting the results, the elevated 
      predose plasma L-dopa concentration (12 h after DM-1992 administration) lends 
      objective support to our findings, suggesting that phase 3 studies are warranted.
CI  - (c) 2015 International Parkinson and Movement Disorder Society.
FAU - Verhagen Metman, Leo
AU  - Verhagen Metman L
AD  - Rush University Medical Center, Chicago, IL, USA.
FAU - Stover, Natividad
AU  - Stover N
AD  - University of Alabama at Birmingham, AL, USA.
FAU - Chen, Cuiping
AU  - Chen C
AD  - Depomed Inc., Newark, CA, USA.
FAU - Cowles, Verne E
AU  - Cowles VE
AD  - Depomed Inc., Newark, CA, USA.
FAU - Sweeney, Michael
AU  - Sweeney M
AD  - Depomed Inc., Newark, CA, USA.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150402
PL  - United States
TA  - Mov Disord
JT  - Movement disorders : official journal of the Movement Disorder Society
JID - 8610688
RN  - 0 (Antiparkinson Agents)
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/pharmacokinetics/*therapeutic use
MH  - Carbidopa/pharmacokinetics/*therapeutic use
MH  - Cross-Over Studies
MH  - Drug Combinations
MH  - *Drug Delivery Systems
MH  - Female
MH  - Follow-Up Studies
MH  - Gastrointestinal Tract/drug effects/physiology
MH  - Humans
MH  - Levodopa/pharmacokinetics/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Parkinson Disease/*drug therapy
MH  - Severity of Illness Index
MH  - Time Factors
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Parkinson's disease
OT  - carbidopa/levodopa
OT  - efficacy
OT  - gastroretention
OT  - pharmacokinetics
EDAT- 2015/04/08 06:00
MHDA- 2016/06/09 06:00
CRDT- 2015/04/08 06:00
PHST- 2014/07/11 00:00 [received]
PHST- 2015/02/18 00:00 [revised]
PHST- 2015/03/02 00:00 [accepted]
PHST- 2015/04/08 06:00 [entrez]
PHST- 2015/04/08 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
AID - 10.1002/mds.26219 [doi]
PST - ppublish
SO  - Mov Disord. 2015 Aug;30(9):1222-8. doi: 10.1002/mds.26219. Epub 2015 Apr 2.