Randomized trial of IPX066, carbidopa/levodopa extended release, in early Parkinson's disease
Rajesh Pahwa, Kelly E Lyons, Robert A Hauser, Stanley Fahn, Joseph Jankovic, Emmanuelle Pourcher, Ann Hsu, Martin O'Connell, Sherron Kell, Suneel Gupta, APEX-PD Investigators, Steven Cohen, Aaron Ellenbogen, Lawrence Elmer, Ramon Gil, Paul Ginsberg, Jeffrey Gitt, Robert Hauser, Bahman Jabbari, Joseph Jankovic, Jonathan Licht, Margery Mark, William McElveen, Dragos Mihaila, Paul Nausieda, Anette Nieves, Omid Omidvar, Rajesh Pahwa, Sotirios Parashos, Lauren Seeberger, Dee Silver, Natividad Stover, James Tetrud, Winona Tse, Leonard Verhagen, Cheryl Waters, David Grimes, Douglas Hobson, Mandar Jog, Tilak Mendis, Emmanuelle Pourcher, Katrin Gross-Paju, Toomas Toomsoo, Guntis Karelis, Andrejs Millers, Ilona Bickuviene, Valmantas Budrys, Sigla ceponaviciute, Antanas Vaitkus, Vaineta Valeikiene, Nicolae Carciumaru, Lacramioara Perju Dumbrava, Manuela Rodica Marceanu, Sanda Maria Nica, Cristian Dinu Popescu, Mihaela Adriana Simu, Joszef Atilla Szasz, Volodymyr Abramov, Lyudmila Dzyak, Karaban Karaban, Olexandr Kozyolkin, Volodymyr Lebedynets, Nataliya Lytvynenko, Tamara Mishchenko, Sergry Moskovko, Yanush Sanotskiy, Olena Statinova, Rajesh Pahwa, Kelly E Lyons, Robert A Hauser, Stanley Fahn, Joseph Jankovic, Emmanuelle Pourcher, Ann Hsu, Martin O'Connell, Sherron Kell, Suneel Gupta, APEX-PD Investigators, Steven Cohen, Aaron Ellenbogen, Lawrence Elmer, Ramon Gil, Paul Ginsberg, Jeffrey Gitt, Robert Hauser, Bahman Jabbari, Joseph Jankovic, Jonathan Licht, Margery Mark, William McElveen, Dragos Mihaila, Paul Nausieda, Anette Nieves, Omid Omidvar, Rajesh Pahwa, Sotirios Parashos, Lauren Seeberger, Dee Silver, Natividad Stover, James Tetrud, Winona Tse, Leonard Verhagen, Cheryl Waters, David Grimes, Douglas Hobson, Mandar Jog, Tilak Mendis, Emmanuelle Pourcher, Katrin Gross-Paju, Toomas Toomsoo, Guntis Karelis, Andrejs Millers, Ilona Bickuviene, Valmantas Budrys, Sigla ceponaviciute, Antanas Vaitkus, Vaineta Valeikiene, Nicolae Carciumaru, Lacramioara Perju Dumbrava, Manuela Rodica Marceanu, Sanda Maria Nica, Cristian Dinu Popescu, Mihaela Adriana Simu, Joszef Atilla Szasz, Volodymyr Abramov, Lyudmila Dzyak, Karaban Karaban, Olexandr Kozyolkin, Volodymyr Lebedynets, Nataliya Lytvynenko, Tamara Mishchenko, Sergry Moskovko, Yanush Sanotskiy, Olena Statinova
Abstract
Objective: IPX066 is an extended release carbidopa/levodopa formulation designed to rapidly attain and maintain therapeutic plasma concentrations for a prolonged duration, allowing dosing intervals of approximately 6 h. The objective was to assess the efficacy, safety, and impact on quality of life of IPX066 in the treatment of levodopa-naive Parkinson's disease (PD) patients.
Methods: This was a randomized, double-blind, placebo-controlled, 30-week study of 381 levodopa-naïve patients assigned to placebo or IPX066 containing 145, 245 or 390 mg of levodopa administered three times daily (TID). The primary efficacy measure was change from Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (Part II) + motor scores (Part III), at 30 weeks. Secondary outcome measures included UPDRS total and subscores, patient and clinician global impressions (PGI-I, CGI-I), and the Parkinson's Disease Questionnaire (PDQ-39).
Results: All IPX066 dosages were superior to placebo throughout the study and at 30 weeks (P < 0.0001). The mean improvement in UPDRS Parts II + III at 30 weeks compared to baseline was 11.7, 12.9, and 14.9 points for the three dosages and 0.6 points for placebo (P < 0.0001, all dosages). PDQ-39 total scores improved with IPX066 (P ≤ 0.034, all dosages). The most commonly reported adverse events with IPX066 included nausea, dizziness, and headache. No unexpected drug-related serious adverse events were reported.
Conclusion: IPX066 provided significant clinical benefits at the three dosages tested compared to placebo and was well tolerated in levodopa-naive PD patients. Of the dosages tested, IPX066 145 mg TID appeared to provide the best overall balance between efficacy and safety.
Keywords: Carbidopa/levodopa; Clinical trial; Parkinson's disease; Randomized controlled trial.
Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed