Rajesh Pahwa1, Kelly E Lyons2, Robert A Hauser3, Stanley Fahn4, Joseph Jankovic5, Emmanuelle Pourcher6, Ann Hsu7, Martin O'Connell8, Sherron Kell9, Suneel Gupta10. 1. University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: rpahwa@kumc.edu. 2. University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: kelly.lyons@att.net. 3. University of South Florida, Tampa, FL, USA. Electronic address: rhauser@health.usf.edu. 4. Columbia University, New York, NY, USA. Electronic address: sf1@columbia.edu. 5. Baylor College of Medicine, Houston, TX, USA. Electronic address: josephj@bcm.edu. 6. Quebec Memory and Motor Skills Disorders Research Clinic, Quebec City, Canada. Electronic address: psa@riq.qc.ca. 7. Impax Pharmaceuticals, Hayward, CA, USA. Electronic address: annhsu@impaxlabs.com. 8. Impax Pharmaceuticals, Hayward, CA, USA. Electronic address: moconnell@impaxlabs.com. 9. Impax Pharmaceuticals, Hayward, CA, USA. Electronic address: skell@impaxlabs.com. 10. Impax Pharmaceuticals, Hayward, CA, USA. Electronic address: sgupta@impaxlabs.com.
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 toplacebo 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.
RCT Entities:
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 PDpatients. Of the dosages tested, IPX066 145 mg TID appeared to provide the best overall balance between efficacy and safety.