A Multi-centre, Randomised, Double-blind, Placebo- and Entacapone-controlled, Parallel Group Study of the Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients with Motor Fluctuations

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2006-002937-20-CZ
• Date of registration: 24/10/2006
• Prospective Registration: Yes
• Primary sponsor: Eisai Limited
• Public title: A Multi-centre, Randomised, Double-blind, Placebo- and Entacapone-controlled, Parallel Group Study of the Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients with Motor Fluctuations
• Scientific title: A Multi-centre, Randomised, Double-blind, Placebo- and Entacapone-controlled, Parallel Group Study of the Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients with Motor Fluctuations
• Date of first enrolment: 14/12/2006
• Target sample size: 702
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002937-20
• 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: yes Placebo: yes Other: no

Countries of recruitment

Czech Republic, Estonia, France, Hungary, Italy, Latvia, Lithuania, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients with idiopathic PD fulfilling the (United Kingdom [UK])
Parkinson’s disease Society Brain Bank diagnostic criteria (7), with a good response to
levodopa.
2. Patients must have been diagnosed with idiopathic PD at = 30 years of age. In
addition the onset of symptoms associated with Parkinson’s disease must have
occurred = 30 years of age.
3. Patients must have predictable motor fluctuations of the wearing OFF type with the
presence of at least 2 hrs of OFF time during the waking day (excluding the morning
OFF time) as evidenced by diary cards completed at screening and confirmed by
diary data collected in the 3-day diaries completed before randomisation.
4. Before patients are randomised, they must be able to show that they are able to
accurately complete the diary cards. During the diary-training period at Screening
Visit 1, there must be diary evidence of at least one transition of OFF to ON or from
ON to OFF.
5. Patients must rate between II-IV on the Hoehn &Yahr (8) scale when in an OFF state.
6. Patients must be taking optimised levodopa (plus dopamine decarboxylase inhibitors
[DDI]) therapy (according to the Investigator’s opinion) at least 3 times during the
waking day (not including bedtime/night time dose) up to a maximum of 8 doses
daily (including bedtime/night time dose).
7. Patients who are treated with DA or MAOB inhibitors or other anti-PD drugs must be
on optimised and stable doses for at least 4 weeks prior to the Screening visit and
must remain stable throughout the study. (revised per Amendment 02) Only levodopa
dosage can be adjusted downwards in the first 6 weeks of the double-blind treatment
phase.
8. In the Investigator’s opinion, patients must be able to distinguish their own motor
states and the absence or presence of troublesome or non-troublesome dyskinesias.
9. In the Investigator’s opinion, patients are able to complete the study including the
completion of the home diary cards and are capable of giving full written informed
consent.
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:
1. Pregnant or lactating women.
2. Women of child-bearing potential unless infertile (including surgically sterile) or
practicing effective contraception (e.g. abstinence, intrauterine device or barrier
method plus hormonal method). These patients must have a negative serum ß-human
chorionic gonadotrophin (ß-HCG) test at the initial screening visit (Visit 1) and a
negative urine pregnancy test at the baseline visit (Visit 3). These patients must also
be willing to remain on their current form of contraception for the duration of the
study. Postmenopausal women may be recruited but must be amenorrhoeic for at
least 1 year to be considered of non-child-bearing potential as determined by the
Investigator.
3. Patients with a past or present history of drug or alcohol abuse as per Diagnostic and
Statistical Manual of Mental Disorders (4th edition; DSM IV) criteria.
4. Patients with a past (within 1 year) or present history of psychotic symptoms
requiring anti-psychotic treatment. Patients may be taking anti-depressant
medication; however, the dose must be stable for 4 weeks prior to the Screening visit.
Use of anti-psychotic medication including clozapine and quetiapine is prohibited.
5. Patients with a past (within 1 year) or present history of major depression, suicidal
ideation or suicide attempts.
6. Patients with unstable abnormalities of the hepatic, renal, cardiovascular, respiratory,
gastro-intestinal, haematological, endocrine or metabolic systems that might
complicate assessment of the tolerability of the study medication.
7. Patients who have a past or present history of liver impairment, neuroleptic malignant
syndrome, non-traumatic rhabdomyolysis or pheochromocytoma.
8. Patients with significantly elevated liver enzymes (abnormal bilirubin or serum
transaminase levels of more than 1.5 times the upper normal limit).
9. Patients with current or prior treatment (within 4 weeks prior to the Screening visit)
with medication known to induce the enzyme CYP3A4 (refer to Section 9.8.2 for list
of prohibited medications).
10. Current or prior treatment (within 4 weeks prior to the Screening visit) with pergolide
(only applies to patients entering after April 5, 2007), cabergoline (effective as of the
date of the IRB/IEC approval of this amendment), tolcapone, methyldopa, budipine,reserpine, quetiapine or intermittent use of either liquid forms of levodopa or
subcutaneous apomorphine. (revised per Amendment 02)
11. Current treatment with non selective MAOA/B or combination of selective MAOA
and selective MAOB inhibitors.
12. Patients with a known hypersensitivity to the active substance or to any of the
excipients of entacapone.
13. Patients with previous stereotactic surgery (e.g. pallidotomy) for PD or with planned
stereotactic surgery during the study period.
14. Patients receiving or with planned (next 6 months) deep brain stimulation.
15. Patients who have received entacapone previously or are currently using entacapone.
16. Patients who have received an investigational product within 4 weeks prior to the
Screening visit or patients who have participated in a previous study with E2007.
(revised per Amendment 02)
17. Patients with clinically significant cognitive impairment (Mini-Mental State
Examination [MMSE] <24 or fulfilling DSM IV criteria for dementia due to PD).
18. Patients with conditions affecting the peripheral or central sensory system unless
related to PD (such as mild sensory or pain syndromes limited to OFF periods) tha

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

Health Condition(s) or Problem(s) studied

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

Intervention(s)

Product Name: E2007
Product Code: MARS
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: E2007
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Comtess
Product Name: Entacapone
Pharmaceutical Form: Capsule*
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To compare the efficacy of one dose strength (4 mg) of E2007 with that of placebo on motor function in patients with Parkinson's disease (PD) who are on optimised and stabilised therapy and experience end-of-dose “wearing off” motor fluctuations.

Primary end point(s): To compare the efficacy of one dose strength (4 mg) of E2007 with that of placebo on
motor function in patients with PD who are on optimised and stabilised therapy and
experience end-of-dose “wearing off” motor fluctuations.

Secondary Objective: To demonstrate that the efficacy of entacapone on motor function in patients with PD who are on optimised and stabilised therapy and experience end-of-dose “wearing off” motor fluctuations, is consistent with what has been reported in other clinical trials.

To compare the safety and tolerability of E2007 to that of placebo.

Other:
To assess the efficacy of E2007 on levodopa induced dyskinesias as measured by the Unified Parkinson’s Disease Rating Score (UPDRS) part IV dyskinesia items and the patient diary.
To compare the effects of E2007 to that of placebo on levodopa
use.

Secondary ID(s)

E2007-G000-309

2006-002937-20-EE