E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Levodopa induced dyskinesia in Parkinson's disease patients |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013916 |
E.1.2 | Term | Dyskinesia |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 |
To evaluate the safety and tolerability of ADX48621 in Parkinson's
disease patients following four weeks of dosing. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ADX48621 compared with placebo in reducing
levodopa induced dyskinesia in patients with Parkinson's disease.
To evaluate the effect of ADX48621 on symptoms of Parkinson's disease
and patient ability to function.
To evaluate the effect of co-administration of ADX48621 on L-dopa
efficacy. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. willing and able to provide written informed consent
2. age 30 to 75 years, inclusive
3. outpatient with idiopathic PD according to the UK Parkinson's Disease
Society Brain Bank Clinical Diagnosis Criteria (UKPDSBBCDC)
4. on an optimized PD treatment regimen with a stable dose of antiparkinsonian
medication for at least four weeks before the Screening
Visit (levodopa, DDIs, COMT inhibitors, dopamine agonists and MAO-B
inhibitors).
5. treated with a daily L-dopa dose (immediate or extended release
formulation) between 300 and 1500 mg divided into a minimum of three
doses per day
6. experiences dyskinesia for at least three months prior to study entry
7. experiences moderately disabling dyskinesia (screening visit UPDRS
33 score ≥ 2)
8. has an mAIMS score at baseline ≥ 7 with a score ≥ 3 in at least one
body area
9. has the ability to communicate adequately with the study staff and to comply with the requirements of the entire study, with the help of a
carer if applicable |
|
E.4 | Principal exclusion criteria |
1. has more than 4 hours, i.e. 8 missing or incorrectly completed entries
in the Screening diary
2. surgical treatment for Parkinson's disease (e.g. Deep Brain
Stimulation, within the last year or planned during the study)
3. unstable co-existing psychiatric disease including cognitive
impairment that, according to the Investigator, could interfere with the
conduct of the study
4. has a known clinically significant allergy or known hypersensitivity to
drugs that, in the opinion of the Investigator, may affect the patient's
safety
5. has clinically significant abnormal laboratory parameters at screening,
in particular, liver or renal functions tests greater than 1.5 times the
upper limit of normal (ULN) or any other clinically significant
biochemical or hematological abnormality as determined by the
Investigator
6. is taking or has taken less then 4 weeks prior to Screening excluded
drugs: NMDA antagonists including amantadine and memantine as well
as amphetamines, cocaine, topiramate, sodium valproate, apomorphine,
MAO-A inhibitors, dopamine antagonists including metoclopramide,
phenothiazines and any antipsychotics, potent inhibitors of CYP1A2, i.e.
fluvoxamine or fluoroquinolone antibiotics, potent inhibitors of CYP2C8,
i.e. gemfibrozil.
7. has known or suspected human immunodeficiency virus (HIV) or
hepatitis B or C.
8. has a history of a significant medical condition that may affect the
safety of the patient or preclude adequate participation in the study,
including but not limited to orthostatic hypotension causing syncope,
uncontrolled ischemic heart disease, uncontrolled brady- or
tachyarrhythmias, coronary obstructive pulmonary disease, chronic
obstructive pulmonary disease, arrhythmias, diabetes and epilepsy.
9. is pregnant or breast-feeding. Female patients who are of childbearing
potential must be using adequate contraceptive methods (e.g.
oral contraceptive, double-barrier method, intra-uterine device, intramuscular
hormonal contraceptive), and have a negative pregnancy test
at Screening.
10. has received any investigational drug within 30 days of Screening. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Efficacy, primary efficacy variable: dyskinesia severity measured by
mAIMS AUC0-3 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | No |
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 |
Austria |
France |
United States |
|
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
|
The end of the trial is defined as last patient last visit |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |