Carbidopa/Levodopa/Entacapone Versus Immediate Release (IR) Carbidopa/Levodopa on Non-motor Symptoms in Patients With Idiopathic Parkinson's Disease and Demonstrating Non-motor Symptoms of Wearing Off

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

Official Title
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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 Off

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Carbidopa/levodopa/entacapone
* Drug: Immediate release carbidopa/levodopa


Participation Criteria
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Eligibility Criteria
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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. Also there should not have been a deterioration of 1 point or more in another non-motor item.(all criteria must be fulfilled) Be taking a stable dose of immediate release (IR) carbidopa/levodopa for at least 21 days prior to randomization at an equivalent total daily dose of immediate release (IR) carbidopa/levodopa between 300 to 800 mg. Dosing should be either 3 to 6 times per day. 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; Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carbidopa/levodopa/entacapone<br> | Drug: Carbidopa/levodopa/entacapone<br>* Carbidopa/levodopa/entacapone 25/100/200 mg tablets plus placebo immediate release carbidopa/levodopa capsules, administered orally for 8 weeks. Total daily dosage and frequency of dosing for each patient was determined by the investigator and stabilized upon entry into the study.<br>* Other names: Stalevo®;|
| Active Comparator: Immediate release carbidopa/levodopa<br> | Drug: Immediate release carbidopa/levodopa<br>* Immediate release carbidopa/levodopa 25/100 mg capsules plus placebo carbidopa/levodopa/entacapone tablets, administered orally for 8 weeks. The maximum daily dose is 800 mg. Total daily dosage and frequency of dosing for each patient was determined by the investigator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Non-motor Score of the Quantitative Wearing-Off Questionnaire 9 Item (QWOQ-9) | The QWOQ-9 is a self-rated questionnaire used to assess motor and non-motor symptoms of Parkinson's disease. The 4 non-motor symptoms are each measured on a five item (0-4) Likert scale, reflecting the severity of the item from not present to very severe. The range of possible score values of the non-motor subscale of the QWOQ-9 is 0 to 16. A higher score indicates greater disability. A negative change score indicates improvement. | Baseline to 15 minutes prior to 2nd dose at Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline on the Motor Score of the Quantitative Wearing-Off Questionnaire 9 Item (QWOQ-9) | The QWOQ-9 is a self-rated questionnaire used to assess motor and non-motor symptoms of Parkinson's disease. The 5 motor symptoms are each measured on a five item (0-4) Likert scale, reflecting the severity of the item from not present to very severe. The range of possible score values of the motor subscale of the QWOQ-9 is 0 to 20. A higher score indicates greater disability. A negative change score indicates improvement. | Baseline to 15 minutes prior to 2nd dose at Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic Parkinson's disease, carbidopa/levodopa/entacapone, non-motor symptoms, motor-symptoms