Parkinson’s disease (PD) patients with end-of-dose wearing-off (motor fluctuations)
Conditions
Interventions
Product Name: Levodopa 75 mg A CAP
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: levodopa
CAS Number: 59-92-7
Other descriptive name: LEVODOPA
Concentration unit: mg milligr
Sponsors
Orion Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent (IC) obtained. - Male or female patients with idiopathic PD according to the UK brain bank criteria with end-of-dose wearingoff (motor fluctuations). - Hoehn and Yahr stage 2-4 performed during the ON-state. - At least 2 hours of OFF-time on each day (measured by the ON/OFF diary) on 3 consecutive days at the end of the screening period just before the baseline visit (visit 1). - Treatment with 4-8 daily doses of levodopa/AADC inhibitor, either combined with entacapone (levodopa/AADC inhibitor combined with Comtess/Comtan or as Stalevo) or without entacapone, with a total daily levodopa dose from > 400 mg to = 1200 mg with entacapone, or from > 400 mg to = 1400 mg without entacapone. One evening dose of controlled release formulation, 1 morning dose of soluble levodopa/AADC inhibitor, or both, as needed are allowed. - Unchanged levodopa/AADC inhibitor with or without entacapone, and other antiparkinsonian medication (dopamine agonists, monoamine oxidase [MAO] B inhibitor, amantadine and/or anticholinergics with doses recommended by the manufacturer), if any, for at least 4 weeks before the screening visit. - Age of 30 years or above. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: - Secondary or atypical Parkinsonism. - Current use of tolcapone or opicapone (within 4 weeks before the screening visit). - Previous tolerability problems with entacapone, tolcapone and opicapone. - Concomitant treatment with apomorphine, MAO-A inhibitors or non-selective MAO inhibitors (within 4 weeks before the screening visit). - Concomitant treatment with drugs having antidopaminergic action including alpha-methyldopa, reserpine and antipsychotic drugs (also D2 receptor blocking antiemetics except domperidone). As an exception to prohibit use of antipsychotic drugs, 1 evening dose of an atypical antipsychotic is allowed. - Use of concomitant medicine which is predominantly metabolised by CYP3A4 and which has a narrow therapeutic window such as ergot alkaloids, carbamazepine, cyclosporin, macrolides (sirolimus and tacrolimus), quinidine or fentanyl. - Current use of warfarin (within 4 weeks before the screening visit). - Inability to refrain from use of any iron preparations during the study. - Disabling dyskinesias. - Problematic hallucinations within 3 months before the screening visit. - Symptomatic orthostatic hypotension. - Current dementia (Mini Mental State Examination [MMSE] score 1.25 x upper limit of normal (ULN) at screening. - Any other abnormal value of laboratory, vital signs or ECG (such as QTcF prolongation = 450 ms) that may 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). - Patients with pre-planned surgery requiring hospitalisation during the study. - Known hypersensitivity to active substances or to any of the excipients of the study treatments. - Blood donation or loss of significant amount of blood within 60 days before screening visit. - Participation in a drug study within 60 days before the first treatment period. - 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. - Failure to demonstrate acceptable/appropriate use of the ON/OFF diary despite adequate training during the screening visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy and safety of ODM-104 in combination with modified release (MR) levodopa and 65 mg of carbidopa in the treatment of Parkinson’s disease (PD) patients with end-of-dose wearing-off (motor fluctuations) compared to active control (Stalevo). ;Secondary Objective: To explore how to switch patients on levodopa/aromatic amino acid decarboxylase (AADC) Inhibitor or levodopa/AADC inhibitor + entacapone directly to ODM-104 in combination with MR levodopa and 65 mg of carbidopa, to determine the effect size for phase III planning and to study levodopa daily dose and dosing frequency of the combination.;Primary end point(s): The statistical hypothesis of this study is to show superiority of the new ODM-104 + levodopa + carbidopa combination in treatment of PD patients with end-of-dose motor symptoms when compared to active control (Stalevo) using a 2 x 2 crossover design. The change from baseline in duration of daily OFF-time, ON-time without dyskinesia, ON-time with nontroublesome dyskinesia, ON-time with troublesome dyskinesia, or asleep, as measured by the ON/OFF diary, will be analysed using an analysis of covariance (ANCOVA) model for crossover design. All analyses will use the average of 3 consecutive ON/OFF diary days and will be stratified by current treatment with or without entacapone at randomisation. ;Timepoint(s) of evaluation of this end point: The subjects will record their PD status using the ON/OFF diary on 3 consecutive days before visits 1, 3 and 5. In completing their ON/OFF diaries, the subjects will record whether they are OFF, ON without dyskinesia, ON with non-troublesome dyskinesia, ON with troublesome dyskinesia, or asleep, in 30 minutes intervals. OFF-time recorded by the ON/OFF diary will be used as the primary efficacy variable. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The change from baseline in UPDRS parts I-IV and the sum of UPDRS parts II and III (‘total score’) assessed by the investigator, and CGI assessed by the investigator and the subject will be analysed using an ANCOVA model for crossover design. The change from baseline in Schwab and England activities of daily living scale assessed by the investigator will be analysed using an ANCOVA model for crossover design. The PDSS-2, total daily levodopa dose and the number of daily levodopa doses will be summarised using descriptive statistics.;Timepoint(s) of evaluation of this end point: UPDRS I-IV and CGI will be assessed by the investigator at baseline (week 0) and at weeks 4 and 8. The investigator is instructed to interview and examine the subject 30 to 90 minutes following the study treatment administration. CGI will be assessed also by the subject at baseline and at weeks 4 and 8. Schwab and England activities of daily living scale will be assessed by the investigator at baseline and at weeks 4 and 8. PDSS-2 will be assessed by the subject at baseline and at weeks 4 and 8. | — |
Countries
Finland, Germany, Hungary, Latvia
Contacts
Public Contactclinicaltrials@orionpharma.com
Orion Corporation
Outcome results
None listed