Official Title: “A 12-Week, Multi-Center, Randomized, Prospective, Open-Label, Blinded Rater, Crossover Study of the Effects of Immediate-Release Carbidopa/Levodopa Versus Carbidopa/Levodopa/Entacapone on Markers of Event-Related Potentials (ERPs) in Patients With Idiopathic Parkinson's Disease and End-of-Dose Wearing Off”

This study will evaluate the effects of immediate release (IR) carbidopa levodopa versus the effects of immediate-release carbidopa/levodopa on ERP parameters in patients with idiopathic PD.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: February 2009

Intervention(s) in this Clinical Trial

• Drug: carbidopa/levodopa
• Drug: Carbidopa/Levodopa/Entacapone

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Immediate-Release Carbidopa/Levodopa
• Active Comparator: 2
  • Carbidopa/Levodopa/Entacapone

Primary Measures

• To evaluate the mean latency of the P300 component of the event-related potentials (ERPs) at four hours post study-drug administration

Secondary Measures

• Mean latency of the P300 component of ERPs at pre-dose and 1 hours post-dose study drug administration
• Mean latency of the N100 component of ERPs at pre-dose, 1 hour post-dose and 4 hours post-dose study drug administration
• Pharmacokinetics at 9.25 and 12.55 hours post dose

Inclusion Criteria:

• 1. Male or female patients aged 45 to 75 years (inclusive)
• 2. Patients with an MMSE score of at least 25 at the screening visit.
• 3. Patients who experience EODWO, which is the re-emergence of PD symptoms during the waking hours, as determined by a WOQ-9 score of at least one motor symptom of wearing off
• 4. Patients taking a stable dose of immediate-release carbidopa/levodopa for at least 4 weeks prior to randomization, at an equivalent total daily dose of levodopa between 300 to 600 mg/day.
• 5. Patients who, in the investigator's judgement, are capable of satisfying the requirements of the protocol
• 6. Patients who are willing and able to give written informed consent according to legal requirements.

Exclusion Criteria:

• 1. Diagnosis of secondary parkinsonism, atypical Parkinson's disease, or history, signs, or symptoms suggesting these diagnoses.
• 2. Unstable Parkinson's disease as determined by the investigator.
• 3. Disabling dyskinesia (a score of >2 on the Unified Parkinson's Disease Rating Scale
• [UPDRS] question #32, or a score of >2 on UPDRS question #33).
• 4. Treatment with carbidopa/levodopa controlled-release or extended-release formulations (bedtime administration is acceptable). The use of controlled-release carbidopa/levodopa is not allowed on the evening before the visits in which efficacy assessments occur.
• 5. Concominant or previous treatment with certain medications or supplements as specified in the protocol.
• 6. Patients who are unable to comply with the dosing requirements of the protocol, such that the first dose of study medication will be taken after the time of the first EEG and the second dose will be taken after completion of the third EEG.
• 7. Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR; diagnosis of 1. dementia (of any cause); 2. moderate or severe major depression, present independent from the time of first diagnosis of PD, as defined by a QIDS-SR16 score of > 15; or 3. generalized anxiety disorder or panic disorder if made prior to the diagnosis of PD.
• 8. DSM-IV-TR diagnosis of alcohol or substance abuse (excluding nicotine or caffeine) during the 3 months prior to randomization) or alcohol or substance dependence (excluding nicotine or caffeine) during the 6 months prior to randomization. Alcohol should be avoided within the 12 hours preceding the Week 6 and Week 12 visits.
• 9. Nicotine use of >5 cigarettes (or equivalent in other forms of administration) per day. Nicotine use will not be permitted on the day of the Week 6 and Week 12 visits.
• 10. Ingestion of >4 caffeinated beverages (or equivalent in other forms of administration) per day.
• 11. History of major head injury, including skull fracture or a penetrating head injury, or a history of brain surgery.
• 12. Past or current treatment by deep brain stimulation.
• 13. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
• 14. Hearing loss or impairment that may prevent reliability of test results using auditory evoked potentials.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Novartis

Overall Clinical Trial Officials and Contacts

Overall Contact: Novartis Pharmaceuticals 862-778-8300 

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00601978

Study ID Number: CELC200AUS15

ClinicalTrials.gov Identifier: NCT00601978

Health Authority: United States: Food and Drug Administration