Parkinson's DiseasePhase 3NCT00360308
Efficacy, Safety and Tolerability of E2007 in Levodopa Treated Parkinson's Disease Patients With Motor Fluctuations
A Phase 3 study testing E2007 in people with Parkinson's Disease, run by Eisai Limited at 1 site in France.
Trial summary
Randomised, double-blind, double dummy, parallel group design. Following the screening period patients will be randomised at the baseline visit, in a 1:1:1 manner, to one of three treatment arms; 4 mg E2007, 200 mg entacapone (with each dose of levodopa) or placebo. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- E2007
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 723 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2006to Apr 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients with idiopathic PD fulfilling the (United Kingdom [UK]) Parkinson's disease Society Brain Bank diagnostic criteria, with a good response to levodopa.
- 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.
- 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.
- 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.
- Patients must rate between II IV on the Hoehn \&Yahr (8) scale when in an OFF state.
- 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).
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- 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. Only levodopa dosage can be adjusted downwards in the first 6 weeks of the double blind treatment phase.
- 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.
- 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.
Who cannot join
- Pregnant or lactating women.
- 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 B-human chorionic gonadotrophin (B-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.
- 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.
- 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.
- Patients with a past (within 1 year) or present history of major depression, suicidal ideation or suicide attempts.
- 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.
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- Patients who have a past or present history of liver impairment, neuroleptic malignant syndrome, non traumatic rhabdomyolysis or pheochromocytoma.
- Patients with significantly elevated liver enzymes (abnormal bilirubin or serum transaminase levels of more than 1.5 times the upper normal limit).
- Patients with current or prior treatment (within 4 weeks prior to the Screening visit) with medication known to induce the enzyme CYP3A4.
- 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.
- Current treatment with non selective MAOA/B or combination of selective MAOA and selective MAOB inhibitors.
- Patients with a known hypersensitivity to the active substance or to any of the excipients of entacapone.
- Patients with previous stereotactic surgery (e.g., pallidotomy) for PD or with planned stereotactic surgery during the study period.
- Patients receiving or with planned (next 6 months) deep brain stimulation.
- Patients who have received entacapone previously or are currently using entacapone.
- 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.
- Patients with clinically significant cognitive impairment (Mini Mental State Examination [MMSE] <24 or fulfilling DSM IV criteria for dementia due to PD).
- 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) that could interfere with the evaluation of any such symptoms caused by the study drug.
- Patients with any condition that would make the patient, in the opinion of the Investigator, unsuitable for the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
Randomised, double-blind, double dummy, parallel group design. Following the screening period patients will be randomised at the baseline visit, in a 1:1:1 manner, to one of three treatment arms; 4 mg E2007, 200 mg entacapone (with each dose of levodopa) or placebo. The first 4 weeks of the double blind phase will be used to titrate patients on the E2007 arm from 2 mg up to the maintenance dose of 4 mg. Patients randomised to entacapone or placebo will have dummy up titrations to maintain the blind. Following this titration phase, patients will remain on the maintenance dose for a further 14 weeks.
Patients will have visits at 2, 4, 6, 10, 14 and 18 weeks after baseline. A follow up visit will be performed at Week 22.
Read more
A home diary will be completed in which patients rate themselves as either:
- "OFF"
- "ON" without dyskinesias
- "ON" with non-troublesome dyskinesias
- "ON" with troublesome dyskinesias
- Asleep
These entries will be completed every 30 minutes during the waking day and will be completed for three consecutive days immediately prior to visits at Baseline, Weeks 6, 10, 18 and 22.
At Baseline (Day 0), week 10 and 18 the Unified Parkinson's Disease Rating Scale (UPDRS - Parts I, II , III and IV) will be performed.
At the end of the treatment period (Week 18), patients will undergo final efficacy and safety assessments and will stop taking the study medication they were receiving. They will be seen 4 weeks later for a follow up visit.
- Conditions
- Parkinson's Disease
- Being tested
- Placebo, E2007
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
E2007Drug
E2007Drug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | matching E2007 and matching entacapone Receives: Drug: Placebo |
| E2007 | Active comparator | 2 mg once daily in the evening, Weeks 0→2 (2 weeks) and 4 mg once daily in the evening, Weeks 2→18. Receives: Drug: E2007 |
| Entacapone | Active comparator | 200 mg with each dose of Levodopa. Receives: Drug: E2007 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 18 (Including LOCF Data)
Efficacy assessments were recorded by subjects using a home diary card. ON state is when medication is providing benefits to mobility, slowness, and stiffness. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.
Measured: Baseline and Week 18
Secondary outcomes (3)
Mean Change From Baseline in UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 18 (Including LOCF Data)
Efficacy assessments were recorded by subjects using a home diary card. Unified Parkinson's Disease (PD) Rating Scale (UPDRS) is a standardized assessment of the symptoms and signs of PD. Part II assesses Activities of Daily Living (ADL) based on 13 items, such as speech, hygiene, and falling. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.
Measured: Baseline and Week 18
Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 18 (Including LOCF Data)
Efficacy assessments were recorded by subjects using a home diary card. UPDRS is a standardized assessment of the symptoms and signs of PD. Part III assesses motor activity, based on 14 items, such as gait, facial expression, and rigidity. Participants receive a score of 0-4 points per item, with a higher score indicating more severe symptoms. ON state is when medication is providing benefits to stiffness, slowness, and tremor.
Measured: Baseline and Week 18
Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 18 (Including LOCF Data)
Efficacy assessments were recorded by subjects using a home diary card. ON state is when medication is providing benefits to stiffness, slowness, and tremor.
Measured: Baseline and Week 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2006 (estimated)
- Study startNov 2006
- Primary completionApr 2008
- Study completionApr 2008
Why it stopped: Study stopped due to lack of efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 723 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Squillacote, M.D., Study director, Eisai Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00360308
- Sponsor's protocol ID
- E2007-G000-309
- Other IDs
- 2006-002937-20
- Status last verified
- Aug 2013
- First submitted
- 2 Aug 2006
- Last updated
- 11 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00360308
- Acronym / sponsor ID
- E2007-G000-309
- Conditions
- Parkinson's Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped due to lack of efficacy.
- Enrolment
- 723 participants (actual)
- Lead sponsor
- Eisai LimitedIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 4 Aug 2006 (estimated)
- Results
- Posted 22 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomised, double-blind, double dummy, parallel group design. Following the screening period patients will be randomised at the baseline visit, in a 1:1:1 manner, to one of three treatment arms; 4 mg E2007, 200 mg entacapone (with each dose of levodopa) or placebo. The first 4 weeks of the double blind phase will be used to titrate patients on the E2007 arm from 2 mg up to the maintenance dose of 4 mg. Patients randomised to entacapone or placebo will have dummy up titrations to maintain the blind. Following this titration phase, patients will remain on the maintenance dose for a further 14 weeks.
Patients will have visits at 2, 4, 6, 10, 14 and 18 weeks after baseline. A follow up visit will be performed at Week 22.
A home diary will be completed in which patients rate themselves as either:
- "OFF"
- "ON" without dyskinesias
- "ON" with non-troublesome dyskinesias
- "ON" with troublesome dyskinesias
- Asleep
These entries will be completed every 30 minutes during the waking day and will be completed for three consecutive days immediately prior to visits at Baseline, Weeks 6, 10, 18 and 22.
At Baseline (Day 0), week 10 and 18 the Unified Parkinson's Disease Rating Scale (UPDRS - Parts I, II , III and IV) will be performed.
At the end of the treatment period (Week 18), patients will undergo final efficacy and safety assessments and will stop taking the study medication they were receiving. They will be seen 4 weeks later for a follow up visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebomatching E2007 and matching entacapone |
| E2007 | Active comparator | Drug: E20072 mg once daily in the evening, Weeks 0→2 (2 weeks) and 4 mg once daily in the evening, Weeks 2→18. |
| Entacapone | Active comparator | Drug: E2007200 mg with each dose of Levodopa. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female patients with idiopathic PD fulfilling the (United Kingdom [UK]) Parkinson's disease Society Brain Bank diagnostic criteria, with a good response to levodopa.
- 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.
- 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.
- 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.
- Patients must rate between II IV on the Hoehn \&Yahr (8) scale when in an OFF state.
Key exclusion criteria (19 listed)
- Pregnant or lactating women.
- 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 B-human chorionic gonadotrophin (B-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.
- 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.
- 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.
- Patients with a past (within 1 year) or present history of major depression, suicidal ideation or suicide attempts.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo | Drug | Placebo |
| E2007 | Drug | E2007 |
| E2007 | Drug | Entacapone |
Primary outcome
Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 18 (Including LOCF Data)
Time frame: Baseline and Week 18
Efficacy assessments were recorded by subjects using a home diary card. ON state is when medication is providing benefits to mobility, slowness, and stiffness. OFF state is when medication has worn off and is no longer providing benefits with regard to stiffness, slowness, and tremor.
3 secondary outcomes
Mean Change From Baseline in UPDRS Part II (ADL) Score in Total Daily OFF Time to Week 18 (Including LOCF Data)
Time frame: Baseline and Week 18
Mean Change From Baseline in UPDRS Part III (Motor) Score in ON State (Hours) to Week 18 (Including LOCF Data)
Time frame: Baseline and Week 18
Mean Change From Baseline in Total Daily ON Time (Without Dyskinesias or With Non-troublesome Dyskinesias) (Hours) to Week 18 (Including LOCF Data)
Time frame: Baseline and Week 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Squillacote, M.D. study director
Eisai Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing E2007 in people with Parkinson's Disease, run by Eisai Limited at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in Total Daily OFF Time (Hours) to Week 18 (Including LOCF Data) (time frame: Baseline and Week 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2014.