Comparison of two levodopa treatments, ODM-104 and Stalevo, in Parkinson's disease patients who have motor fluctuations.

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2015-004507-23-DE
• Date of registration: 13/01/2016
• Prospective Registration: Yes
• Primary sponsor: Orion Corporation
• Public title: Comparison of two levodopa treatments, ODM-104 and Stalevo, in Parkinson's disease patients who have motor fluctuations.
• Scientific title: Efficacy and safety of ODM-104 compared to a standard combination (Stalevo®); a randomised, double-blind, crossover proof-of-concept study in patients with Parkinson’s disease and end-of-dose wearing-off. - COMPOC
• Date of first enrolment: 25/04/2016
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004507-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Finland, Germany, Hungary, Latvia

Contacts

• Name: [e-mail]
• Affiliation: Orion Corporation

• Name: [e-mail]
• Affiliation: Orion Corporation

Key inclusion & exclusion 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:
- 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 < 26).
- Problematic impulse control disorders (ICDs), such as pathological gambling, hypersexuality or compulsive
shopping within 6 months before the screening visit.
- History of neuroleptic malignant syndrome (NMS), non-traumatic rhabdomyolysis, or both.
- Any neurosurgical intervention for the treatment of PD, including deep brain stimulation (DBS).
- Narrow-angle glaucoma or pheochromocytoma.
- Any active malignant cancer.
- Clinically significant cardiovascular (e.g. ischaemic heart disease, ventricular or supraventricular arrhythmias), pulmonary, GI (e.g. inflammatory bowel disease), 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 > 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

Parkinson’s disease (PD) patients with end-of-dose wearing-off (motor fluctuations)

Intervention(s)

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 milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Levodopa 100 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 milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Levodopa 125 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 milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Levodopa 150 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 milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Carbidopa 65 mg capsule
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Carbidopa
CAS Number: 38821-49-7
Other descriptive name: CARBIDOPA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 65-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: ODM-104
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: na
Other descriptive name: ODM-104
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceut

Primary Outcome(s)

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.

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.

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).

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 Outcome(s)

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.

Secondary ID(s)

2015-004507-23-LV

3112004

Source(s) of Monetary Support

Orion Corporation