| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Parkinson’s disease levodopa induced dyskinesia (PD-LID) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061536 |
| E.1.2 | Term | Parkinson's disease |
| 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 |
| The primary objective of this study is to evaluate the efficacy of Eltoprazine in reducing LID in patients with PD and to examine the dose response, to establish the minimal effective dose of Eltoprazine to treat LID. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of Eltoprazine in PD patients following multiple weeks of dosing.
• To evaluate Eltoprazine effects on patient function and underlying symptoms of PD.
• To evaluate the utility of the Kinesia Objective Motor Assessment to objectively quantify dyskinesia and Parkinsonian motor symptoms. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A patient will be invited to participate if he/she meets the following inclusion criteria:
1. willing and able to provide written informed consent
2. age 30 to 85 years, inclusive
3. outpatient with idiopathic PD according to the UK Parkinson’s Disease Society Brain Bank Clinical Diagnosis Criteria (UKPDSBBCDC)
4. on a PD treatment regimen with a stable dose of anti-Parkinsonian 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 levodopa dose (immediate or extended release formulation) more than 300 mg per day divided into at least three doses
6. treated with levodopa for at least three years prior to study entry
7. has been experiencing levodopa induced peak-dose dyskinesia for at least three months prior to study entry
8. experiences disabling dyskinesia (Screening Visit MDS-UPDRS Part IV question 4.2 score ≥2)
9. has dyskinesia for, on average, >25% of the waking day based on patient reported dyskinesia (tablet diaries) during the second week of the screening period
10. has the ability to communicate adequately with the study staff and to comply with the requirements of he entire study, with the help of a caregiver if applicable |
|
| E.4 | Principal exclusion criteria |
A patient will be excluded from study participation if he/she meets any of the following
criteria:
1. inability to use the Kinesia 360 system (tablet or motion sensors) correctly,
diaries not completed in a timely manner or two or more hours’ worth of missing “waking day entries” or times PD-LID medication taken missing
2. surgical treatment for PD (e.g. DBS), within the last six months or planned during the study
3. unstable co-existing psychiatric disease including psychosis, depression or
cognitive impairment that, according to the Investigator, could interfere with the conduct of the study
4. has an MMSE score of <24
5. has a known clinically significant allergy or known hypersensitivity to drugs that, in the opinion of the Investigator, may affect the patient’s safety
6. has moderate or severe renal or severe hepatic impairment and/or has clinically significant abnormal laboratory parameters at screening, in particular, liver or renal function 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
7. treatment with selective serotonin re-uptake inhibitors (SSRI) or any combined serotonin-norepinephrine re-uptake inhibitors (SNRI) such as tryptizol, citalopram, escitalopram, sertraline, mianserin, mirtazapin, paroxetin, venlafaxine and St John’s Wort, within four weeks prior to the Screening Visit.
8. other medication with the potential for drug-interactions (MAO-A inhibitors,
apomorphine, aripiprazol, carbamazepine, clozapine, phenytoin, tramadol,
quetiapine, varfaine, valproic acid). Patients taking amantadine may be included if the amantadine is being used according to its indication for the treatment of PD and not specifically for dyskinesia and the dose remains stable throughout the trial. Patients taking amantadine will comprise no more than 25% of the study population
9. No clinically significant 12-lead ECG abnormalities and with a QTc value of
<450 ms for men and <460 ms for women.
10. has a current history of a clinically significant and uncontrolled 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 tachy-arrhythmias, chronic obstructive pulmonary disease, diabetes and epilepsy
11. is pregnant or breast-feeding. Female patients who are of child-bearing potential must be using adequate contraceptive methods (e.g. oral contraceptive, doublebarrier method, intra-uterine device, intra-muscular hormonal contraceptive), and have a negative pregnancy test at Screening
12. has received any other investigational medicinal product within 30 days of Screening
13. is a member of, or relative of, the study site staff and/or employees or consultants of Amarantus BioScience |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Safety and Tolerability
• Safety and tolerability will be assessed by physical and neurological examination, HR and BP, 12-lead ECG, hematology and biochemistry assessments, PK assessments, use of concomitant medications, and adverse events (AEs) and serious adverse events (SAEs) will be recorded.
Efficacy:
Clinical impact of dyskinesia measured by total UDysRS score at baseline (Day 0) and at the end of each Treatment Period on Days 21, 42, 63 and 84.
Responder Criterion: a 20% reduction in total UDysRS score from Day 0, measured on Days 21, 42, 63 and 84 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety:
Day 0 (baseline) and at the end of each Treatment Period on Days 21, 42, 63 and 84, and on Day 94 Final Follow-up Visit.
Efficacy:
Day 0 (baseline) and at the end of each Treatment Period on Days 21, 42, 63 and 84. |
|
| E.5.2 | Secondary end point(s) |
1. Amount of time spent asleep
2. “ON” time without dyskinesia, with any dyskinesia and by severity
3. “OFF” time with and without tremor and by severity.
4. Clinician observed dyskinesia severity using UDysRS Part 3 and 4
5. Kinesia One system (discrete monitoring) scores measured over a number of different TMTs (rest tremor, postural tremor, kinetic tremor, finger tapping, hand opening/closing and hand pronation/supination including determination of bradykinesia)
6. MDS-UPDRS Part III Score (motor examination based on 18 items). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints for secondary endpoints 1,2,3: During the two days at the end of the second week of the screening period (baseline) and the two days at the end of each Treatment Period.
Timepoints for secondary endpoints 4,5,6: Baseline (Day 0) and at the end of each Treatment Period visit i.e. on Days 21, 42, 63 and 84, at 90 (±30) minutes post dosing with levodopa. |
|
| 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 | Yes |
| 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 | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| 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 | No |
| E.8.1.6 | Cross over | Yes |
| 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.8.2.4 | Number of treatment arms in the trial | 4 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 8 |
| 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 |
| France |
| Germany |
| Sweden |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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 | 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 |
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