Official Title: “An 8-Week, Prospective, Randomized, Double-Blind, Double-Dummy, Active-Controlled, Multi-Center Comparison Study of the Effects of Carbidopa/Levodopa/Entacapone Versus Immediate Release Carbidopa/Levodopa on Non-Motor Symptoms in Patients With Idiopathic Parkinson's Disease and Demonstrating Non-Motor Symptoms of Wearing”

The purpose of this study is to test the effects of carbidopa/levodopa/entacapone compared to the effects of immediate-release carbidopa/levodopa on end-of-dose wearing off in persons who have Parkinson's disease.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

Intervention(s) in this Clinical Trial

• Drug: Carbidopa/levodopa/entacapone, IR carbidopa/levodopa
• Drug: Carbidopa/levodopa/entacapone, IR carbidopa/levodopa

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Carbidopa/levodopa/entacapone plus immediate release carbidopa/levodopa placebo
• Placebo Comparator: 2
  • Immediate release carbidopa/levodopa plus Carbidopa/levodopa/entacapone placebo

Primary Measures

• Compare effects of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa on the non-motor symptoms in patients with idiopathic PD and non-motor symptoms of wearing off using the non-motor subscale of the QWOQ-9 item from baseline to end of study
  • Time Frame: 8 weeks
    Safety Issue?: No

Secondary Measures

• Compare effects of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa on the motor symptoms in patients with idiopathic PD and non motor symptoms of wearing off using the motor subscale of the QWOQ-9 (mQWOQ-9) from baseline to end of study.
  • Time Frame: 8 weeks
    Safety Issue?: Yes
• Compare effects of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa on the non-motor symptoms in patients with idiopathic PD and non-motor symptoms of wearing off using the Hamilton Anxiety Scale (HAM-A) from baseline to end of study.
  • Time Frame: 8 weeks
    Safety Issue?: Yes
• Compare effects of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa on apathy and depression using the Apathy Scale and Quick Inventory of Depressive Symptomatology-Self Reporting 16-item (QIDS-SR16) respectively, from baseline to end of study.
  • Time Frame: 8 weeks
    Safety Issue?: Yes
• Assess occurrence and severity of symptoms of impulse control, as measured with the Modified Minnesota Impulsive Disorder Interview assessment (Modified MIDI), of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa from baseline to end of study.
  • Time Frame: 8 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• Be aged 30 to 85 years.
• Be male or female - female patients must be either not of childbearing potential (defined as post menopausal for at least one year or surgically incapable of bearing children), or must be practicing contraceptive methods as outlined in the protocol.
• Have a clinical diagnosis of idiopathic Parkinson's Disease, exhibiting at least 2 of 3 symptoms (rigidity, resting tremor, bradykinesia)
• Have non-motor symptoms of end of dose wearing off i.e., the presence of at least one non-motor symptom of Parkinson's Disease which improves with the next immediate release (IR) carbidopa/levodopa dose as determined by the Quantitative Wearing-Off Questionnaire 9 and investigator's assessment. At least one non-motor item has to show a severity of at least 2 points (of a maximum of 4) and show an improvement of at least 1 one hour after immediate release (IR) carbidopa/levodopa administration.
• (all criteria must be fulfilled)
• Be taking a stable dose of immediate release (IR) carbidopa/levodopa for at least 28 days prior to randomization at an equivalent total daily dose of immediate release (IR) carbidopa/levodopa between 300 to 600 mg. Dosing should be either 3 or 4 times per day.
• Be capable of satisfying the requirements of the protocol and must be willing and able to give informed consent according to legal requirements.

Exclusion Criteria:

• Have a previous history of being non-responsive to entacapone or tolcapone treatment or having experienced a serious or severe adverse event(s) which resulted in the discontinuation of treatment from the previous use of entacapone or tolcapone; current treatment with entacapone or tolcapone or discontinued treatment with either therapy or discontinued less than 60 days before randomization;
• Have a history, signs, or symptoms suggesting a diagnosis of secondary or atypical parkinsonism;
• Have unstable Parkinson's Disease requiring frequent booster doses;
• Disabling dyskinesias, indicated by a score of greater than 1 on Unified Parkinson
• Disease Rating Scale question #32, or a score of greater than 1 on Unified Parkinson
• Disease Rating Scale question #33;
• Have a history or current diagnosis of psychotic features according to the investigator;
• Have a history or current diagnosis of symptoms of an impulse control disorder according to a screening assessment with the modified Minnesota Impulsive Disorders Interview and the investigator's judgment;
• Have a diagnosis of Bipolar Disorder I or II according to the Diagnostic Statistical Manual, Fourth Edition;
• Demonstrate indications of marked suicidal tendencies as assessed by the investigator;
• Have undergone psychotherapy or psychiatric pharmacotherapy, currently or within 28 days prior to randomization;
• If female, be pregnant, trying to become pregnant or nursing an infant;
• Diagnostic and Statistical Manual, Fourth Edition, Text Revision; [American
• Psychiatric Association, 2000] diagnosis of 1. dementia (of any cause); 2. moderate or severe major depression, present independent from the time of first diagnosis of Parkinson's Disease, as defined by a Quick Inventory of Depressive Symptomatology
• Self Rating 16 score of > 15; or 3. generalized anxiety disorder or panic disorder if made prior to the diagnosis of Parkinson's Disease;
• Have received treatment with MAO-inhibitors;
• Diagnostic and Statistical Manual, Fourth Edition, Text Revision 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 Screening, Baseline, Week 2 and Week 8 visits;
• Diagnostic and Statistical Manual, Fourth Edition, Text Revision diagnosis of dysthymia within the last 12 months;
• Have a history or current diagnosis 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.
• Other protocol-defined inclusion/exclusion criteria may apply

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Novartis

Overall Clinical Trial Officials and Contacts

Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals  

Overall Contact: Novartis Pharmaceuticals 862-778-8300 

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00642356

Study ID Number: CELC200AUS14

ClinicalTrials.gov Identifier: NCT00642356

Health Authority: United States: Food and Drug Administration