A double-blind, delayed-start trial of rasagiline in Parkinson's disease
C Warren Olanow, Olivier Rascol, Robert Hauser, Paul D Feigin, Joseph Jankovic, Anthony Lang, William Langston, Eldad Melamed, Werner Poewe, Fabrizio Stocchi, Eduardo Tolosa, ADAGIO Study Investigators, Jose Bueri, Nelida Garretto, Oscar Gershanik, Rolando Giannaula, Federico Micheli, Elisabeth Wolf, Mark Guttman, Douglas Hobson, Mandar Jog, David King, Tilak Mendis, Janis Miyasaki, Michel Panisset, Emmanuelle Pourcher, Ali Rajput, Ranjit Ranawaya, Joseph Tsui, Pierre Cesaro, Philippe Damier, Alain Destee, Franck Durif, Tarik Slaoui, François Tison, François Viallet, Günther Deuschl, Thomas Gasser, Albert Ludolph, Christian Oehlwein, Horst Przuntek, Gerd Reifschneider, Alfons Schnitzler, Claudia Trenkwalder, Magdolna Bokor, Agnes Katona, Julia Lajtos, Janos Nikl, Annamaria Takats, Attila Valikovics, Samih Badarny, Ruth Djaldetti, Nir Giladi, Sharon Hassin, Jose Martin Rabey, Avinoam Reches, Miguel Schwartz, Itzhak Wirguin, Alberto Albanese, Annarita Bentivoglio, Ubaldo Bonuccelli, Stefano Calzetti, Giancarlo Comi, Luigi Curatola, Carlo Ferrarese, Paolo Lamberti, Roberto Marconi, Emilia Martignoni, Giuseppe Meco, Stefano Ruggieri, Fabrizio Stocchi, M A M Bomhof, Ad Hovestadt, Jean Michel Krul, K L Leenders, Luis Cunha, Joaquim Ferreira, Ovidiu Alexandru Bajenaru, Nicolae Carciumaru, Angelo Corneliu Bulboaca, Ioan Pascu, Mihaela Simu, Matilde Calopa, Jose Manuel Fernández García, Jaime Kulisevsky, Cristobal Linazasoro, Francesco Miquel, Ignacio Javier Posada, Maria Jose Martí, David Burn, Doug MacMahon, Roger Barker, Neil Allen, Peter Barbour, John Bertoni, Kersi Bharucha, Sudeshna Bose, Edward Drasby, Rodger Elble, Lawrence Elmer, Bradley Evans, Stewart Factor, Hubert Fernandez, Joseph Friedman, Keith Hull, Lawrence Golbe, John Goudreau, Thomas Guttuso, Mohamed Hassan, Robert Hauser, Neal Hermanowicz, Melissa Houser, Howard Hurtig, Stuart Isaacson, Danna Jennings, Aikaterini Kompoliti, John Morgan, John Murphy, Paul Nausieda, Rajesh Pahwa, Sotirios Parashos, Padraig O'Suilleabhain, Brad Racette, Stephen Reich, John Roberts, Ted Rothstein, Alok Sahay, Marie Saint-Hilaire, Mya Schiess, Burton Scott, Joohi Shahed, Tanya Simuni, Carlos Singer, Robert Smith, Lynn Struck, James Sutton, David Swope, Michele Tagliati, James Tetrud, Daniel Togasaki, Ray Watts, C Warren Olanow, Olivier Rascol, Robert Hauser, Paul D Feigin, Joseph Jankovic, Anthony Lang, William Langston, Eldad Melamed, Werner Poewe, Fabrizio Stocchi, Eduardo Tolosa, ADAGIO Study Investigators, Jose Bueri, Nelida Garretto, Oscar Gershanik, Rolando Giannaula, Federico Micheli, Elisabeth Wolf, Mark Guttman, Douglas Hobson, Mandar Jog, David King, Tilak Mendis, Janis Miyasaki, Michel Panisset, Emmanuelle Pourcher, Ali Rajput, Ranjit Ranawaya, Joseph Tsui, Pierre Cesaro, Philippe Damier, Alain Destee, Franck Durif, Tarik Slaoui, François Tison, François Viallet, Günther Deuschl, Thomas Gasser, Albert Ludolph, Christian Oehlwein, Horst Przuntek, Gerd Reifschneider, Alfons Schnitzler, Claudia Trenkwalder, Magdolna Bokor, Agnes Katona, Julia Lajtos, Janos Nikl, Annamaria Takats, Attila Valikovics, Samih Badarny, Ruth Djaldetti, Nir Giladi, Sharon Hassin, Jose Martin Rabey, Avinoam Reches, Miguel Schwartz, Itzhak Wirguin, Alberto Albanese, Annarita Bentivoglio, Ubaldo Bonuccelli, Stefano Calzetti, Giancarlo Comi, Luigi Curatola, Carlo Ferrarese, Paolo Lamberti, Roberto Marconi, Emilia Martignoni, Giuseppe Meco, Stefano Ruggieri, Fabrizio Stocchi, M A M Bomhof, Ad Hovestadt, Jean Michel Krul, K L Leenders, Luis Cunha, Joaquim Ferreira, Ovidiu Alexandru Bajenaru, Nicolae Carciumaru, Angelo Corneliu Bulboaca, Ioan Pascu, Mihaela Simu, Matilde Calopa, Jose Manuel Fernández García, Jaime Kulisevsky, Cristobal Linazasoro, Francesco Miquel, Ignacio Javier Posada, Maria Jose Martí, David Burn, Doug MacMahon, Roger Barker, Neil Allen, Peter Barbour, John Bertoni, Kersi Bharucha, Sudeshna Bose, Edward Drasby, Rodger Elble, Lawrence Elmer, Bradley Evans, Stewart Factor, Hubert Fernandez, Joseph Friedman, Keith Hull, Lawrence Golbe, John Goudreau, Thomas Guttuso, Mohamed Hassan, Robert Hauser, Neal Hermanowicz, Melissa Houser, Howard Hurtig, Stuart Isaacson, Danna Jennings, Aikaterini Kompoliti, John Morgan, John Murphy, Paul Nausieda, Rajesh Pahwa, Sotirios Parashos, Padraig O'Suilleabhain, Brad Racette, Stephen Reich, John Roberts, Ted Rothstein, Alok Sahay, Marie Saint-Hilaire, Mya Schiess, Burton Scott, Joohi Shahed, Tanya Simuni, Carlos Singer, Robert Smith, Lynn Struck, James Sutton, David Swope, Michele Tagliati, James Tetrud, Daniel Togasaki, Ray Watts
Abstract
Background: A therapy that slows disease progression is the major unmet need in Parkinson's disease.
Methods: In this double-blind trial, we examined the possibility that rasagiline has disease-modifying effects in Parkinson's disease. A total of 1176 subjects with untreated Parkinson's disease were randomly assigned to receive rasagiline (at a dose of either 1 mg or 2 mg per day) for 72 weeks (the early-start group) or placebo for 36 weeks followed by rasagiline (at a dose of either 1 mg or 2 mg per day) for 36 weeks (the delayed-start group). To determine a positive result with either dose, the early-start treatment group had to meet each of three hierarchical end points of the primary analysis based on the Unified Parkinson's Disease Rating Scale (UPDRS, a 176-point scale, with higher numbers indicating more severe disease): superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36, superiority to delayed-start treatment in the change in the score between baseline and week 72, and noninferiority to delayed-start treatment in the rate of change in the score between weeks 48 and 72.
Results: Early-start treatment with rasagiline at a dose of 1 mg per day met all end points in the primary analysis: a smaller mean (+/-SE) increase (rate of worsening) in the UPDRS score between weeks 12 and 36 (0.09+/-0.02 points per week in the early-start group vs. 0.14+/-0.01 points per week in the placebo group, P=0.01), less worsening in the score between baseline and week 72 (2.82+/-0.53 points in the early-start group vs. 4.52+/-0.56 points in the delayed-start group, P=0.02), and noninferiority between the two groups with respect to the rate of change in the UPDRS score between weeks 48 and 72 (0.085+/-0.02 points per week in the early-start group vs. 0.085+/-0.02 points per week in the delayed-start group, P<0.001). All three end points were not met with rasagiline at a dose of 2 mg per day, since the change in the UPDRS score between baseline and week 72 was not significantly different in the two groups (3.47+/-0.50 points in the early-start group and 3.11+/-0.50 points in the delayed-start group, P=0.60).
Conclusions: Early treatment with rasagiline at a dose of 1 mg per day provided benefits that were consistent with a possible disease-modifying effect, but early treatment with rasagiline at a dose of 2 mg per day did not. Because the two doses were associated with different outcomes, the study results must be interpreted with caution. (ClinicalTrials.gov number, NCT00256204.)
2009 Massachusetts Medical Society
Source: PubMed