C Warren Olanow1,2, Karl Kieburtz1,3, Mika Leinonen1,4, Lawrence Elmer5, Nir Giladi6, Robert A Hauser7, Olga S Klepiskaya8, David L Kreitzman9, Mark F Lew10, David S Russell11, Shaul Kadosh12, Pninit Litman13, Hadas Friedman13, Nurit Linvah13, For The P B Study Group1. 1. Clintrex LLC, Rye, New York, USA. 2. Mount Sinai School of Medicine, New York, New York, USA. 3. University of Rochester School of Medicine, Rochester, New York, USA. 4. 4Pharma AB, Stockholm, Sweden. 5. Gardner-McMaster Parkinson Center, University of Toledo, Toledo, Ohio, USA. 6. 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. 7. University of South Florida Parkinson's Disease and Movement Disorders Center, NPF Center of Excellence, Tampa, Florida, USA. 8. University of Colorado School of Medicine, Denver, Colorado, USA. 9. Parkinson's Disease and Movement Disorder Center of Long Island, Commack, New York, USA. 10. University of Southern California (USC)/Keck School of Medicine, Los Angeles, California, USA. 11. Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. 12. StatExcellence Ltd, Nesher, Israel. 13. Pharma Two B Ltd, Rehovot, Israel.
Abstract
BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: P2B001 offers a promising treatment option for patients with early PD with good clinical efficacy and a low risk of adverse events.
RCT Entities:
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: P2B001 offers a promising treatment option for patients with early PD with good clinical efficacy and a low risk of adverse events.
Authors: József Attila Szász; Károly Orbán-Kis; Viorelia Adelina Constantin; Csongor Péter; István Bíró; István Mihály; Kinga Szegedi; Antal Balla; Szabolcs Szatmári Journal: Neuropsychiatr Dis Treat Date: 2019-04-05 Impact factor: 2.570