A multicenter, randomized, double blind, parallel-group placebo and pramipexole controlled study to assess efficacy and safety of SLV308 monotherapy in the treatment of patients with early stage Parkinson’s disease. - The Vermeer study

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-000678-57-NL
• Date of registration: 04/04/2007
• Prospective Registration: No
• Primary sponsor: Solvay pharmaceuticals
• Public title: A multicenter, randomized, double blind, parallel-group placebo and pramipexole controlled study to assess efficacy and safety of SLV308 monotherapy in the treatment of patients with early stage Parkinson’s disease. - The Vermeer study
• Scientific title: A multicenter, randomized, double blind, parallel-group placebo and pramipexole controlled study to assess efficacy and safety of SLV308 monotherapy in the treatment of patients with early stage Parkinson’s disease. - The Vermeer study
• Date of first enrolment: 03/08/2006
• Target sample size: 330
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-000678-57
• 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: yes Placebo: yes Other: no

Countries of recruitment

Czech Republic, Estonia, France, Germany, Italy, Lithuania, Netherlands, Portugal, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subjects who provide written informed consent before starting any study specific procedures.
2. The clinical diagnosis of subjects must meet the criteria for "Diagnosis of idiopathic Parkinson’s Disease" according to the modified UKPDS Brain Bank criteria (see Appendix 16.3).
3. Modified Hoehn and Yahr up to stage 3.
4. Unified Parkinson’s Disease Rating Scale motor score (part 3) must have a total of at least 10 at baseline.
5. Out patients.
6. Subjects of = 30 years old.
7. For anti-PD medication other than SLV308 and pramipexole, the following criteria apply:
- Subjects may have had treatment with L-dopa formulations or dopamine agonists up to a total of 90 days.
- Subjects must have stopped the use of L-dopa and/or dopamine agonists for at least 90 days prior to baseline.
- Efficacious previous treatment 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 and dopamine agonists (i.e., selegiline, rasagiline, anti-cholinergics, amantadine) is allowed if the doses have been kept stable for at least 28 days prior to baseline and during the study.
8. Male and female, females must be of non-childbearing potential or:
- have a negative serum ß-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 Visit 1, 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. 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.
2. 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.
3. Presence of dyskinesias, motor fluctuations or loss of postural reflexes.
4. Subjects with a history of non-response (according to both the clinician and the subject) to an adequate course of L-dopa or a dopamine agonist.
5. Subjects for whom previous treatment with dopamine agonists needed to be terminated because of the induction of psychosis (e.g. hallucinations) and/or sleep attacks.
6. Treatment within 60 days prior to baseline with monoamine oxidase (MAO) inhibitors (other than selegiline and rasagiline), alpha-methyldopa or metoclopramide; treatment within last 30 days before baseline with parenteral ergots, methylphenidate, amphetamine, beta-blockers for treating tremor, isoprenaline, adrenaline, dopamine, dobutamide, reserpine, flunarizine or cinnarizine. (See also Section 7.8.2).
Related to Psychiatric and Neurological Disorders
7. Current diagnosis or history of drug or alcohol abuse (Diagnostic and Statistical Manual of Mental Disorders [DSM]-IV criteria), within 12 months prior to Visit 1.
8. Current primary psychiatric diagnosis of acute psychotic disorder or other primary psychiatric diagnoses, such as bipolar disorder or major depressive disorder (DSM-IV criteria).
9. Subjects who, based on history and mental status examination, are considered to be violent (likely to harm themselves or others), or subjects considered at suicidal risk by the investigator.
10. Other psychiatric, neurological or behavioral disorders that may interfere with the conduct or interpretation of the study. Cognitive impairment (Mini Mental State Examination [MMSE] = 24), dementia or significant concomitant neurological disease would also be included under this category.
11. A history of hallucinations, psychosis and/or treatment with antipsychotics within a year from baseline.
12. A history of, or current, seizure disorders (other than febrile seizures in childhood) and subjects requiring treatment with anti-convulsants, whatever the indication.
13. Subjects known with serious symptomatic cerebral disease, cerebrovascular disease, focal neurological lesions (previous brain surgery), or any acute brain trauma requiring treatment with anticonvulsant therapy.
Related to Other Medical Conditions
14. Clinically significant abnormal laboratory data at Visit 1 or any abnormal laboratory value that could interfere with the assessment of safety or efficacy.
15. Current evidence of clinically significant hematological, autoimmune, endocrine, cardiovascular, renal or gastrointestinal disorder that would possibly interfere with the subject’s participation in the study (e.g., treated, controlled and thus stable hypertension is not considered an exclusion criterion).
16. Subjects whose current regimen of medication or condition suggests that it will not remain constant for the duration of study participation will be excluded from the trial.
17. Known unstable insulin dependent diabetes mellitus (treatment control: glycosylated hemoglobi

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

Health Condition(s) or Problem(s) studied

Parkinson 's Disease early stage
MedDRA version: 8.1 Level: LLT Classification code 10013113 Term: Disease Parkinson's

Intervention(s)

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

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

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

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

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

Product Name: SLV308 (mono) hydrochlori

Primary Outcome(s)

Primary end point(s): Criteria for Evaluation:

Efficacy:
UPDRS parts 1, 2 and 3, CGI-Severity (CGI-S), CGI-Improvement (CGI-I) and Parkinson’s Disease Questionnaire (PDQ-39), EQ-5D.

Pharmacokinetics:
Data obtained on population pharmacokinetics of SLV308.

Safety:
Adverse events (AEs), concomitant medications, vital signs, physical examination, electrocardiogram (ECG) and laboratory assessments, Epworth Sleepiness Scale (ESS).

Secondary Objective: The secondary objectives are:

- To investigate the effects of treatment with SLV308 compared to placebo in improving overall PD symptoms, including activities of daily living and clinical global impression (CGI).
- To collect and evaluate data on population-pharmacokinetics of SLV308.
- To investigate the effects of SLV308 treatment on health-related quality of life.
- To compare pramipexole treatment with placebo for testing assay sensitivityand for exploratory purposes only.

The safety objective is to assess safety and tolerability of SLV308 monotherapy in patients with early stage PD.

Main Objective: The primary objective is to provide six months pivotal efficacy data to show that 12-42 mg/day SLV308 monotherapy is superior to placebo with respect to the effect on motor functioning of Parkinson’s disease (PD) patients.

Secondary ID(s)

S308.3.003

2006-000678-57-CZ