Comparing Different Levodopa/Carbidopa/Entacapone Treatment Regimens (PARTEST)
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Carbidopa
Sponsored by
About this trial
This is an interventional prevention trial for Parkinson's Disease focused on measuring Parkinson's Disease, Motor response, Wearing-off
Eligibility Criteria
Inclusion Criteria:
- Written informed consent (IC) obtained.
- Male or female patients with idiopathic PD according to the United Kingdom brain bank criteria with end-of-dose motor fluctuations
- Hoehn and Yahr stage 2-4 performed during the "ON" state.
- Duration of response between 1.5 and 4 hours (based on medical history) to the patient's first morning dose of levodopa/dopa decarboxylase inhibitor (DDCI) with or without entacapone.
- Treatment with 3-8 daily doses of levodopa/DDCI with or without entacapone with a total daily levodopa dose in the range of 300-1200 mg. One evening dose of controlled-release formulation of levodopa/DDCI is allowed provided that it is included in the total of 3-8 daily doses of levodopa/DDCI mentioned above.
- Unchanged levodopa/DDCI with or without entacapone and other antiparkinsonian medication(dopamine agonists, monoamine oxidase [MAO] B inhibitor, amantadine and/or anticholinergics with approved doses), if any, for at least 6 weeks prior to the screening visit.
- Age of 30 years or above
Exclusion Criteria:
- Secondary or atypical parkinsonism.
- Use of tolcapone within 6 weeks prior to the first treatment period.
- Previous tolerability problems with entacapone or tolcapone.
- Concomitant treatment with apomorphine, MAO-A inhibitors or nonselective MAO inhibitors.
- Concomitant treatment with drugs having antidopaminergic action including alpha-methyldopa, reserpine and antipsychotic drugs (also D2 receptor blocking antiemetics except domperidone). As an exception, an evening dose of an atypical antipsychotic is allowed.
- Use of any iron preparations.
- Intensity of dyskinesias which would, in the opinion of the investigator, interfere with the interpretation of motor part (part III of the Unified Parkinson's Disease Rating Scale (UPDRS III) scoring during the levodopa challenge test.
- Currently active hallucinations.
- Severe orthostatic hypotension as judged by the investigator.
- Mini-Mental State Examination (MMSE) score < 26
- History of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis.
- Past or current treatment with deep brain stimulation (DBS) or other surgical treatment for PD.
- Treatment with levodopa or dopamine agonist infusion or injection
- Active malignancy, narrow-angle glaucoma or pheochromocytoma.
- Clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological or psychiatric disorder or any other major concurrent illness that in the opinion of the investigator would interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part into the study.
- Alanine aminotransferase or aspartate aminotransferase > upper limit of normal at screening.
- Any other abnormal value of laboratory, vital signs or electrocardiogra (ECG) which would in the opinion of the investigator interfere with the interpretation of the study results or cause health risk for the subject if he/she takes part into the study.
- Female patients of childbearing potential (i.e. menstruating or less than 2 years postmenopausal) if they are not using proper contraception (hormonal contraception, intrauterine device [IUD] or surgical sterilisation, spermicidal foam in conjunction with condom on male partner).
- Patients with pre-planned elective surgery.
- Known hypersensitivity to active substances or to any of the excipients of the study drugs.
- Participation in a drug study within 60 days prior to entry to this study.
- Any other condition that in the opinion of the investigator would interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part into the study.
Sites / Locations
- Kanta-Hämeen keskussairaala
- ODL Terveys Oy (ODL)
- Porin Lääkäritalo
- Länssjukhuset Ryhov, Medicin/Neurologmottagningen
- Karolinska Universitetssjukhuset Solna, Neurologkliniken
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Stalevo
Placebo
Arm Description
levodopa/carbidopa/entacapone
Outcomes
Primary Outcome Measures
Duration of motor response by UPDRS III
Statistical method for the primary comparison will be analysis of variance (ANOVA) with the following grouping factors: treatment, sequence, subject, and period. Differences between Stalevo and treatment regimen A will be evaluated using orthogonal contrasts with 5% significance level.
Secondary Outcome Measures
Full Information
NCT ID
NCT01296464
First Posted
February 14, 2011
Last Updated
September 9, 2011
Sponsor
Orion Corporation, Orion Pharma
1. Study Identification
Unique Protocol Identification Number
NCT01296464
Brief Title
Comparing Different Levodopa/Carbidopa/Entacapone Treatment Regimens
Acronym
PARTEST
Official Title
Duration of Motor Response After Administration of Experimental Levodopa/Carbidopa/Entacapone Treatment Regimens Compared to Standard Treatment (Stalevo®);a Randomised,Double-blind,Crossover,Multicentre,Single Dose Study in Patients With Parkinson?s Disease and Wearing-off Symptoms
Study Type
Interventional
2. Study Status
Record Verification Date
September 2011
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Orion Corporation, Orion Pharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective is to assess the effect of a single dose of two experimental levodopa/carbidopa/entacapone (L/C/E) treatment regimens versus standard L/C/E treatment regimen in Parkinson's disease (PD) patients with end-of-dose motor fluctuations in terms of duration of motor response after the first morning dose of levodopa. The secondary objective is to evaluate the safety of the L/C/E treatment regimens in patients with PD.
Detailed Description
This is a randomised, double-blind, 3-period crossover study comparing the effects of a single dose of two L/C/E treatment regimens (A and B) and standard L/C/E treatment regimen (Stalevo) on the duration of motor response in PD patients with wearing-off symptoms after the first morning dose of levodopa.
The study consists of a screening visit, 3 treatment visits and an end-of-study visit. Within 14 days of the screening visit, the patients will receive a single morning dose of study drug (either of the two L/C/E treatment regimens) or Stalevo. The order of the 3 treatment periods will be randomised according to a crossover design and the duration of each period is 2 days, followed by a wash-out period (1-9 days) during which the patients will be on their individual standard PD treatment.
Before each study day, patients will arrive at the study centre in the previous evening. The patients' own standard PD treatments will be discontinued at the latest by 22:00 to be continued after completion of the motor part (part III) of the Unified Parkinson's Disease Rating Scale (UPDRS III) next day. After completion of the UPDRS III, patients will return to their own standard PD treatments. Duration of the study will be 2 to 7 weeks per patient, depending on the length of the screening and wash-out periods.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's Disease, Motor response, Wearing-off
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Stalevo
Arm Type
Experimental
Arm Description
levodopa/carbidopa/entacapone
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Carbidopa
Intervention Description
Capsules
Primary Outcome Measure Information:
Title
Duration of motor response by UPDRS III
Description
Statistical method for the primary comparison will be analysis of variance (ANOVA) with the following grouping factors: treatment, sequence, subject, and period. Differences between Stalevo and treatment regimen A will be evaluated using orthogonal contrasts with 5% significance level.
Time Frame
20 minute intervals
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent (IC) obtained.
Male or female patients with idiopathic PD according to the United Kingdom brain bank criteria with end-of-dose motor fluctuations
Hoehn and Yahr stage 2-4 performed during the "ON" state.
Duration of response between 1.5 and 4 hours (based on medical history) to the patient's first morning dose of levodopa/dopa decarboxylase inhibitor (DDCI) with or without entacapone.
Treatment with 3-8 daily doses of levodopa/DDCI with or without entacapone with a total daily levodopa dose in the range of 300-1200 mg. One evening dose of controlled-release formulation of levodopa/DDCI is allowed provided that it is included in the total of 3-8 daily doses of levodopa/DDCI mentioned above.
Unchanged levodopa/DDCI with or without entacapone and other antiparkinsonian medication(dopamine agonists, monoamine oxidase [MAO] B inhibitor, amantadine and/or anticholinergics with approved doses), if any, for at least 6 weeks prior to the screening visit.
Age of 30 years or above
Exclusion Criteria:
Secondary or atypical parkinsonism.
Use of tolcapone within 6 weeks prior to the first treatment period.
Previous tolerability problems with entacapone or tolcapone.
Concomitant treatment with apomorphine, MAO-A inhibitors or nonselective MAO inhibitors.
Concomitant treatment with drugs having antidopaminergic action including alpha-methyldopa, reserpine and antipsychotic drugs (also D2 receptor blocking antiemetics except domperidone). As an exception, an evening dose of an atypical antipsychotic is allowed.
Use of any iron preparations.
Intensity of dyskinesias which would, in the opinion of the investigator, interfere with the interpretation of motor part (part III of the Unified Parkinson's Disease Rating Scale (UPDRS III) scoring during the levodopa challenge test.
Currently active hallucinations.
Severe orthostatic hypotension as judged by the investigator.
Mini-Mental State Examination (MMSE) score < 26
History of neuroleptic malignant syndrome (NMS) and/or non-traumatic rhabdomyolysis.
Past or current treatment with deep brain stimulation (DBS) or other surgical treatment for PD.
Treatment with levodopa or dopamine agonist infusion or injection
Active malignancy, narrow-angle glaucoma or pheochromocytoma.
Clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological or psychiatric disorder or any other major concurrent illness that in the opinion of the investigator would interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part into the study.
Alanine aminotransferase or aspartate aminotransferase > upper limit of normal at screening.
Any other abnormal value of laboratory, vital signs or electrocardiogra (ECG) which would in the opinion of the investigator interfere with the interpretation of the study results or cause health risk for the subject if he/she takes part into the study.
Female patients of childbearing potential (i.e. menstruating or less than 2 years postmenopausal) if they are not using proper contraception (hormonal contraception, intrauterine device [IUD] or surgical sterilisation, spermicidal foam in conjunction with condom on male partner).
Patients with pre-planned elective surgery.
Known hypersensitivity to active substances or to any of the excipients of the study drugs.
Participation in a drug study within 60 days prior to entry to this study.
Any other condition that in the opinion of the investigator would interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part into the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vilho Myllylä, Prof
Organizational Affiliation
Oulu Deaconess Instutute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kanta-Hämeen keskussairaala
City
Hämeenlinna
ZIP/Postal Code
13530
Country
Finland
Facility Name
ODL Terveys Oy (ODL)
City
Oulu
ZIP/Postal Code
90100
Country
Finland
Facility Name
Porin Lääkäritalo
City
Pori
ZIP/Postal Code
28100
Country
Finland
Facility Name
Länssjukhuset Ryhov, Medicin/Neurologmottagningen
City
Jönköping
ZIP/Postal Code
SE-55185
Country
Sweden
Facility Name
Karolinska Universitetssjukhuset Solna, Neurologkliniken
City
Stockholm
ZIP/Postal Code
SE-171 76
Country
Sweden
12. IPD Sharing Statement
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Comparing Different Levodopa/Carbidopa/Entacapone Treatment Regimens
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