E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Parkinson's Desease patients with Motor Fluctuations who are on optimised and stabilised therapy with Levodopa. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061536 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary:
To compare the efficacy of 2mg and 4mg of E2007 and placebo on motor function in patients with Parkinson's disease who are on optimised and stabilised therapy and experience end-of-dose 'wearing off' motor fluctuations. |
|
E.2.2 | Secondary objectives of the trial |
To compare the efficacy of 2mg and 4mg of E2007 and placebo on levodopa-induced dyskinesias
To compare the safety and tolerability of E2007 and placebo
Other
To compare the effects of E2007 and placebo on patients quality of life
To compare the effects of E2007 and placebo on levodopa use
To generate population pharmacokinetic data on E2007 |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female patients with idiopathic PD fulfilling the (UK) Parkinsons
disease Society Brain Bank diagnostic criteria, with a good response to
levodopa.
2. Patients must have been diagnosed with idiopathic PD at ≥ 30 years of age.
3. Patients must have predictable motor fluctuations of the wearing OFF type with
the presence of at least 2 hours 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 at the baseline visit.
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 the
initial screening visit there must be diary evidence of at least one transition of
OFF to ON or from ON to OFF and patients must show 75% concordance with
Investigators completion of the diary card.
5. Patients must rate between II-IV on the Hoehn &Yahr scale when in an OFF
state.
6. Patients must be taking optimised levodopa therapy (according to investigators
opinion) at least 3 times during the waking day (not including bedtime/night
time dose) up to a maximum of 8 doses daily (includes bedtime/night time
dose).
7. Patients who are treated with dopamine agonists, COMT inhibitors or MAOB
inhibitors and other anti-PD drugs must be on optimised and stable doses for at
least 4 weeks prior to initial screening visit and must remain stable throughout
the study. Only levodopa dosage can be adjusted downwards in the first 8
weeks of the double-blind treatment phase.
8. In the Investigators 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 Investigators opinion patients are able to complete the study including
the completion of the home diary cards and capable of giving full written
informed consent. |
|
E.4 | Principal 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, IUD or barrier method
plus hormonal method). These patients must have a negative serum β-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. Fertile men not willing to use reliable contraception and fertile men with
partners not willing to use reliable contraception.
4. Patients with a past or present history of drug or alcohol abuse as per DSM IV
criteria.
5. Patients with a past (within one year) or present history of psychotic symptoms
requiring antipsychotic treatment. Patients may be taking anti-depressant
medication, however the dose must be stable for 4 weeks prior to the baseline
visit. Use of anti-psychotic medication including clozapine and quetiapine is
prohibited even if the indication is for movement disorders.
6. Patients with a past (within one year) or present history of suicidal ideation or
suicide attempts.
7. Patients with unstable abnormalities of the hepatic, renal, cardiovascular,
respiratory, gastro-intestinal, haematological, endocrine or metabolic systems
which might complicate assessment of the tolerability of the study medication.
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 baseline
visit) with medication known to induce the enzyme cytochrome P450 3A4
(refer to section 8.7.2 for list of prohibited meds).
10. Current or prior treatment (within 4 weeks prior to the baseline visit) with
tolcapone, methyldopa, budipine, reserpine, seroquel or intermittent use of
either liquid forms of levodopa or subcutaneous apomorphine.
11. Patients with previous stereotactic surgery (eg pallidotomy) for Parkinsons
disease or with planned stereotactic surgery during the study period.
12. Patients receiving or with planned (next 6months) deep brain stimulation.
13. Patients who have received an investigational product within 4 weeks prior to
the baseline visit or patients that have participated in a previous study with
E2007.
14. Patients with clinically significant cognitive impairment (MMSE <24 and /or fulfilling DSM IV criteria for dementia due to Parkinsons disease).
15. Patients with conditions affecting the peripheral or central sensory system
unless related to Parkinsons disease (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.
16. Patients with any condition that would make the patient, in the opinion of the
Investigator, unsuitable for the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Patient diaries: Change from baseline to final efficacy visit in the mean total daily OFF time (hr)
A secondary analysis of the primary endpoint will be undertaken using a responder analysis: Percentage of patients with total mean daily OFF time reduction of > 1hr. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |