A multicenter, randomized, double-blind, placebo-controlled, parallel group study of SLV308 as adjunct therapy to levodopa in patients with Parkinson’s disease experiencing motor fluctuations. - The Mondriaan study

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-005182-20-LT
• Date of registration: 20/12/2006
• Prospective Registration: Yes
• Primary sponsor: Solvay Pharmaceuticals
• Public title: A multicenter, randomized, double-blind, placebo-controlled, parallel group study of SLV308 as adjunct therapy to levodopa in patients with Parkinson’s disease experiencing motor fluctuations. - The Mondriaan study
• Scientific title: A multicenter, randomized, double-blind, placebo-controlled, parallel group study of SLV308 as adjunct therapy to levodopa in patients with Parkinson’s disease experiencing motor fluctuations. - The Mondriaan study
• Date of first enrolment: 13/02/2007
• Target sample size: 280
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005182-20
• 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: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Latvia, Lithuania

Key inclusion & exclusion criteria

Inclusion criteria:
The clinical diagnosis of subjects must meet the criteria for "Diagnosis of idiopathic Parkinson’s Disease" according to the United Kingdom Parkinson's Disease Society Brain Bank criteria.
Parkinson's disease stage corresponding to 2-4 in the OFF state according to the modified Hoehn and Yahr classification of disease severity.
Stable treatment with l-dopa for at least 28 days prior to randomization, requiring at least three but not more than seven dose periods of l-dopa per day.
Presence of a recognizable ON and OFF motor state (motor fluctuations).
Minimum hours of OFF-time per day of 2.5 hours (during waking hours; including early morning akinesia) as recorded per baseline diaries.
Ability to keep home diary (with or without assistance of caregivers/partners) for recording ON/OFF symptoms and dyskinesia.
For anti-PD medication other than SLV308, the following criteria apply:
-Previous treatment with dopamine agonists should have been terminated at least 90 days prior to baseline.
-Efficacious previous treatment with dopamine agonists is not allowed to be stopped for the sole purpose of enrolling the subject into this study.
-Concurrent anti-PD treatment other than l-dopa (i.e., monoamine oxidase-B inhibitors, anti cholinergics, amantadine) is allowed if the doses have been kept stable for at least 28 days prior to baseline and during the study. The use of catechol-O-methyltransferase inhibitors (COMT) needs to be stable at least 28 days prior to baseline, with the exception of tolcapone which needs to be stabilized at least 6 months prior to baseline. Modification of the dose of COMT inhibitors during the study is allowed only if required in conjunction to modification of l-dopa dose.
Out-patients.
Male and female, females must be of non-childbearing potential or:
-have a negative serum beta-human chorionic gonadotropin, and
-use an accepted form of contraception (a stable dose of contraceptive drug for at least three months or barrier methods: intra uterine device, diaphragm, combination of a condom and spermicide).
Non-childbearing potential is defined as being post-menopausal for at least 24 months prior to the screening visit or surgically sterilized (i.e., tubal ligation or hysterectomy).

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Related to Parkinson’s Disease
1. Presence of complex ‘on-off’ phenomena or ‘yo-yoing’ and/or an abrupt unpredictable loss of efficacy unrelated to the timing of l-dopa administration.
2. Prevalent expression of severely disabling dyskinesias during the waking day, i.e. dyskinesias are present at least 50% of the waking hours (UPDRS Part 4 item 32 equal or more than 3) in combination with a degree of disability which is moderate or higher (UPDRS Part 4 item 33 equal or more than 3).
3. Diagnosis is unclear or a suspicion of other parkinsonian syndromes exists, such as secondary parkinsonism (caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson-plus syndromes (e.g., multiple system atrophy, progressive supranuclear palsy) or heredodegenerative diseases.
4. Subjects who have undergone surgery for the treatment of PD (e.g., pallidotomy, deep brain stimulation, fetal tissue transplantation) or have undergone any other brain surgery.
5. Subjects for whom previous treatment with dopamine agonists needed to be terminated within the last year because of the induction of hallucinations, psychosis and/or intolerable somnolence.

General
1 Treatment with forbidden medications as indicated in Section 7.8.2. of the protocol
2 Exposure to any investigational drug within 60 days prior to the screening visit.
3 Breast feeding or pregnant women.
4 Prior exposure to SLV308.
5 Illiterate patients.
6 Uncooperative attitude or reasonable likelihood for non-compliance with the protocol.
7 Any other reason that, in the investigator’s opinion, prohibits the inclusion of the subjects into the study.



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

Health Condition(s) or Problem(s) studied

Advanced stage Parkinson's disease with motor fluctuations.
MedDRA version: 9.1 Level: LLT Classification code 10034007 Term: Parkinson's disease NOS

Intervention(s)

Product Name: SLV308(mono)hydrochloride
Product Code: SLV308(mono)hydrochloride
Pharmaceutical Form: Film-coated tablet
CAS Number: 269718-83-4
Current Sponsor code: SLV308(mono)hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: SLV308(mono)hydrochloride
Product Code: SLV308(mono)hydrochloride
Pharmaceutical Form: Film-coated tablet
CAS Number: 269718-83-4
Current Sponsor code: SLV308(mono)hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.2-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: SLV308(mono)hydrochloride
Product Code: SLV308(mono)hydrochloride
Pharmaceutical Form: Film-coated tablet
CAS Number: 269718-83-4
Current Sponsor code: SLV308(mono)hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: SLV308(mono)hydrochloride
Product Code: SLV308(mono)hydrochloride
Pharmaceutical Form: Film-coated tablet
CAS Number: 269718-83-4
Current Sponsor code: SLV308(mono)hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: SLV308(mono)hydrochloride
Product Code: SLV308(mono)hydrochloride
Pharmaceutical Form: Film-coated tablet
CAS Number: 269718-83-4
Current Sponsor code: SLV308(mono)hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.0-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: SLV308(mono)hydrochloride
Product Code: SLV308(mono)hydrochloride
Pharmaceutical

Primary Outcome(s)

Secondary Objective: Efficacy objectives
To investigate the effects of SLV308 compared to placebo with respect to increasing ON-time without troublesome dyskinesia based on subjects’ home diaries.
To investigate whether SLV308 is superior to placebo in improving core PD motor symptoms and activities of daily living as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS; sum of Part 2 and 3).
To investigate the effects of SLV308 treatment on health-related quality of life (PDQ-39)

Safety objectives
To collect and evaluate data on the safety and tolerability of SLV308 compared to placebo in subjects with PD treated with l-dopa and experiencing motor fluctuations.
To collect and evaluate data on electrocardiogram (ECG) parameters.

Main Objective: To determine the efficacy of SLV308 compared to placebo in reducing OFF-time in PD patients on l-dopa therapy characterized by motor fluctuations, as based on subjects' home diaries.

Primary end point(s): Efficacy:

ON/OFF/dyskinesia symptom recording in subject home diary, Unified Parkinson’s Disease Rating Scale Parts 1 to 4, Clinical Global Impression (CGI-S and CGI-I), PD Questionnaire (PDQ-39), Hospital Anxiety and Depression Score (HADS), Schwab and England Activities of Daily Living (UPDRS Part 6), modified Hoehn and Yahr (UPDRS Part 5), pain assessment via questionnaire, Visual Analogue Scale and Pain Global Impression (PGI) scale.

Pharmacokinetics:

Data obtained on population pharmacokinetics of SLV308.

Safety:

Adverse events, concomitant medications, vital signs, physical examination, ECG and laboratory assessments.

Secondary ID(s)

S308.3.002