title: A randomized trial of a low-dose Rasagiline and Pramipexole combination (P2B001) in early Parkinson's disease.
abstract: Rasagiline and pramipexole act to improve striatal dopaminergic transmission in PD via distinct and potentially synergistic mechanisms. We performed a placebo-controlled study to determine whether 2 doses of a novel slow-release, low-dose combination of rasagiline and pramipexole (P2B001) are effective and have a good safety profile in patients with early untreated PD.
  
  
  
  Previously untreated patients with early PD were randomized (1:1:1) to once-daily treatment with P2B001 (0.3 mg pramipexole/0.75 mg rasagiline), P2B001 (0.6 mg pramipexole/0.75 mg rasagiline) or placebo in a 12-week multicenter double-blind, placebo-controlled trial. The primary endpoint was the change from baseline to final visit in Total-UPDRS score versus placebo. Secondary measures included responder analyses of patients achieving ≥4 UPDRS point reduction, and changes in Parkinson Disease Quality of Life Scale-39 and UPDRS activities of daily living and motor scores.
  
  
  
  A total of 149 participants were randomized and 136 (91.3%) completed the study. Adjusted mean change from baseline to final visit versus placebo in Total-UPDRS score was -4.67 ± 1.28 points for the P2B001 0.6/0.75 mg group (P = .0004) and -3.84 ± 1.25 points for the 0.3/0.75 mg group (P = .003). Significant benefits were also observed for both doses in the responder analysis (P = .0002 and P = .0001), Parkinson Disease Quality of Life Scale-39 scores (P = .05 and P = .01), and the UPDRS motor (P = .02 and P = .006) and activities of daily living (P = .005 and P = .0004) subscores. Adverse events of P2B001 were comparable to placebo apart from transient nausea and somnolence, which were more common with P2B001 treatment.
  
  
  
  P2B001 offers a promising treatment option for patients with early PD with good clinical efficacy and a low risk of adverse events. © 2017 International Parkinson and Movement Disorder Society.
authors.affiliation: Clintrex LLC, Rye, New York, USA.|Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
authors.affiliation: Clintrex LLC, Rye, New York, USA.|University of Rochester School of Medicine, Rochester, New York, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Kieburtz
authors.affiliation: Clintrex LLC, Rye, New York, USA.|4Pharma AB, Stockholm, Sweden.
authors.forename: Mika
authors.initials: M
authors.lastname: Leinonen
authors.affiliation: Gardner-McMaster Parkinson Center, University of Toledo, Toledo, Ohio, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Elmer
authors.affiliation: Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation (NPF) Center of Excellence, Neurological Institute, Tel-Aviv Medical Center, Sackler School of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.affiliation: University of South Florida Parkinson's Disease and Movement Disorders Center, NPF Center of Excellence, Tampa, Florida, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.affiliation: University of Colorado School of Medicine, Denver, Colorado, USA.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Klepiskaya
authors.affiliation: Parkinson's Disease and Movement Disorder Center of Long Island, Commack, New York, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kreitzman
authors.affiliation: University of Southern California (USC)/Keck School of Medicine, Los Angeles, California, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lew
authors.affiliation: Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Russell
authors.affiliation: StatExcellence Ltd, Nesher, Israel.
authors.forename: Shaul
authors.initials: S
authors.lastname: Kadosh
authors.affiliation: Pharma Two B Ltd, Rehovot, Israel.
authors.forename: Pninit
authors.initials: P
authors.lastname: Litman
authors.affiliation: Pharma Two B Ltd, Rehovot, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Friedman
authors.affiliation: Pharma Two B Ltd, Rehovot, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Linvah
authors.affiliation: Clintrex LLC, Rye, New York, USA.
authors.forename: For
authors.initials: F
authors.lastname: The P B Study Group
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D052160:Benzothiazoles / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D007557:Israel; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D000077487:Pramipexole; D012720:Severity of Illness Index; D014265:Triethylenemelamine; D014481:United States
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D007189:Indans; D018696:Neuroprotective Agents; C031967:rasagiline; D000077487:Pramipexole; D014265:Triethylenemelamine
keywords: P2B001; Parkinson's disease; Pramipexole; Rasagiline