Parkinson's Disease
Conditions
Keywords
Idiopathic Parkinson's disease, carbidopa/levodopa/entacapone, non-motor symptoms, motor-symptoms
Brief summary
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.
Interventions
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.
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.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Non-motor Score of the Quantitative Wearing-Off Questionnaire 9 Item (QWOQ-9) | Baseline to 15 minutes prior to 2nd dose at Week 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Motor Score of the Quantitative Wearing-Off Questionnaire 9 Item (QWOQ-9) | Baseline to 15 minutes prior to 2nd dose at Week 8 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carbidopa/Levodopa/Entacapone 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. | 7 |
| Immediate Release Carbidopa/Levodopa 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. | 7 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 3 |
Baseline characteristics
| Characteristic | Carbidopa/Levodopa/Entacapone | Immediate Release Carbidopa/Levodopa | Total |
|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >= 65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Customized Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 7 | 1 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
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.
Time frame: Baseline to 15 minutes prior to 2nd dose at Week 8
Population: All subjects that were assessed for efficacy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carbidopa/Levodopa/Entacapone | Change From Baseline on the Non-motor Score of the Quantitative Wearing-Off Questionnaire 9 Item (QWOQ-9) | -0.9 Units on a scale | Standard Deviation 0.9 |
| Immediate Release Carbidopa/Levodopa | Change From Baseline on the Non-motor Score of the Quantitative Wearing-Off Questionnaire 9 Item (QWOQ-9) | -0.2 Units on a scale | Standard Deviation 2.49 |
Secondary
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.
Time frame: Baseline to 15 minutes prior to 2nd dose at Week 8
Population: All subjects that were assessed for efficacy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Carbidopa/Levodopa/Entacapone | Change From Baseline on the Motor Score of the Quantitative Wearing-Off Questionnaire 9 Item (QWOQ-9) | -1.2 Units on a scale | Standard Deviation 2.23 |
| Immediate Release Carbidopa/Levodopa | Change From Baseline on the Motor Score of the Quantitative Wearing-Off Questionnaire 9 Item (QWOQ-9) | 0.0 Units on a scale | Standard Deviation 2 |