| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Diagnosys of Early-stage idiopathic Parkinson's Disease for longest 1 year |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10061536 |
| E.1.2 | Term | Parkinson's disease |
|
| 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 first primary study objective is to investigate the superior efficacy of an optimized individual dose of transdermal Lisuride (dose range: 0.2 to 0.4 mg/24 h nominal release rate with patch sizes: 10 cm2 to 40cm2 every second evening) with placebo after 26 weeks, using a sum score of UPDRS parts II (activity of daily living) and III (motor symptoms).
The second primary study objective is to demonstrate non-inferior efficacy of optimized individual dosages of transdermal Lisuride compared with oral Pramipexole (dose range: 1.1 mg to 3.3 mg / day) after 26 weeks, using a sum score of UPDRS parts II and III. The third primary study objective is to investigate the superior efficacy of optimized individual dosages of transdermal Lisuride compared to oral Pramipexole after 26 weeks, using a sum score of UPDRS parts II and III.The fourth primary study objective is to investigate the superior efficacy of optimized individual dosages of transdermal Lisuride compared to oral Pramipexole. |
|
| E.2.2 | Secondary objectives of the trial |
to evaluate further efficacy criteria, quality of life, tolerability and safety of Lisuride TTS patch treatment in comparison to placebo and Pramipexole after 26 weeks of double-blind treatment;
to evaluate efficacy criteria, quality of life, tolerability and safety of Lisuride TTS patch after 26 week open-label treatment between week 27 and week 52) by comparing two treatment regimens with the Lisuride patch (every second day vs. twice a week) as well as with the pooled data. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
QUALITA DELLA VITA
ALTRI SOTTOSTUDI: Questionari e diari del paziente:
1)UPDRS
2)CGI
3)PDSS
4)MADRS
5)PDQ 39
6)EQ-5D
7)ESS
|
|
| E.3 | Principal inclusion criteria |
a) Patient is informed and given ample time and opportunity to think about her/his participation and has given her/his written informed consent
b) Patient is willing and able to comply with all trial requirements
c) Male or female outpatients
d) Age > 30 years
e) Patients with newly diagnosed early-stage of idiopathic Parkinson’s disease for longest 1 year (diagnosis based on the UK Parkinson Brain Bank Diagnostic Criteria for PD, see Appendix 16.3.8) who have not yet received Levodopa therapy (except Levodopa test)
f) Minimum UPDRS motor score of > 12 points at Baseline Visit BL
g) Mini Mental State Examination (MMSE) score of ≥ 27
h) Concomitant diseases are stable and well controlled by medication
i) Female patients must have a negative pregnancy test within 7 days prior to or at Baseline and are required to practice an effective method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility. Effective method of birth control is defined as those which result in a low failure rate (i.e. Pearl Index less than 1% per year) when used consistently and correctly such as:
 A hormonal oral, transdermal, or injectable contraceptive agent with a double-barrier method
 An implantable contraceptive device with a failure rate less than 1% for at least 3 months prior to screening
 Tubal Ligation,
 Vasoectomized partner |
|
| E.4 | Principal exclusion criteria |
a) Patient has non-idiopathic PD due to drugs (e.g. flunarizine, metoclopramide), metabolic neurogenetic disoders (e.g., Wilson’s disease), encephalitis, cerebrovascular disease or other forms of secondary or atypical Parkinsonism such as multisystem atrophy (MSA) or progressive supranuclear palsy)
b) Significant neurological symptoms not accounted for by Parkinson’s disease
c) Current diagnosis of epilepsy, history of seizures as an adult, history of stroke, or transitory ischemic attacks (TIA) within one year prior to the screening visit (visit VS)
d) Patient has a history of pallidotomy, thalamotomy, deep brain stimulation or fetal tissue transplantation or other neurosurgery for Parkinson’s disease
e) History of or active hallucinations or delusions including drug-induced hallucinations, e.g. by dopaminergic therapy
f) Treatment with dopamine agonists within 28 days of the baseline visit (BL)
g) Pre-treatment with Levodopa (except for diagnostic challenge)
h) Pre-treatment during the last 3 months prior to baseline visit 2 or current treatment with MAO-A inhibitors (pargyline, phenelzine, tranylcypromine), reserpine, budipine, alpha-methyldopa
i) Current treatment with CNS active therapy (e.g., sedatives, hypnotics, anti-depressants, anxiolytics, antipsychotics) unless the dose has been stable for at least 28 days prior to the baseline visit (BL) and is likely to remain stable for the duration of Part A of the study.
j) Current treatment with medications which will be eliminated through the renal tubulus system or which inhibit the active renal tubulus secretion (e.g., cimetidine, amantadine)
k) History or presence of dementia demonstrated by the Mini-mental status examination or clinically
l) Presence of major depression according to DSM IV criteria
m) Any evidence or suspicion of any cardiac valvulopathy or any other cardiac disorder which in the opinion of the investigator would put the patient at risk of clinically relevant arrhythmia and/or myocardial infarction, within the last 12 months
n) Clinically relevant hepatic dysfunction as defined as total bilirubin > 2.0 mg/dl or ALT and/or AST greater than two times the upper limit of normal range
o) Clinically relevant renal dysfunction as defined as creatinine > 2.0 mg/dl (> 178 μmol/l)
p) History of syncope and/or severe otherwise symptomatic orthostatic hypotension within the last year or a systolic blood pressure less than 105 mmHg at Screening Visit VS
q) History of significant skin hypersensitivity to adhesive or other transdermal applications, or recent unresolved contact dermatitis
r) Any medical or psychiatric condition or any other clinically significant laboratory abnormalities that, in the opinion of the investigator, would interfere with the appropriate conduct of the study
s) Alcohol or drug abuse in the past three years
t) Females of childbearing potential who are planning to become pregnant, who are pregnant or lactating and/or who are unwilling to use effective means of contraception
u) Patient has previously participated in this trial or patient has previously been assigned to treatment in a trial with Lisuride TTS
v) Participation in other clinical studies in the previous four weeks
w) Pregnancy or lactation
x) QTc > 470 ms at Visit 1 (Bazett correction must be used) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary:
Unified Parkinson’s Disease Rating Scale (UPDRS): sum score of parts II+III:
Absolute change from baseline (Visit BL) to Visit V26.
Secondary:
- UPDRS: scores of parts I, II, III, IV-A, IV-B, IV-C: changes from baseline to Visit V26
- Responder defined by a > 30% improvement between baseline and Visit V26 in the sum score of UPDRS part II + III.
- Parkinson’s Disease Sleep Scale (PDSS) total score: changes from baseline to Visit V26
- Clinical Global Impressions (CGI): CGI-1: global ratings of severity, (difference Visit V26 – baseline (BL), frequency distributions of item 2 “change in condition“ (CGI 2) and “therapeutic effect” (CGI 3)
- Montgomery-Asberg Depression Rating Scale (MADRS) changes from baseline to Visit V26
- EQ-5D: Changes in the Health State score and the EQ-VAS between PDQ 39 baseline and Visit V26
- Parkinson’s Disease Questionnaire (PDQ-39, quality of life) total score: Change from baseline to Visit V26
The same efficacy outcome measures will be analyzed at Visit V52 (end of open-label long-term treatment), compared both to baseline of part A (Day 1, Visit BL) and B (Visit V27).
- Epworth Sleepiness Scale (ESS): Changes in the total score between baseline and Visit.V26 / V52
- Adverse event reporting
- Clinical laboratory tests (hematology, blood chemistry, urinalysis)
- Physical and neurological examination
- Vital signs including symptomatic orthostatic hypotension
- 12-lead ECG including QTc evaluation
- Global rating of tolerability by the investigator (CGI)
- Patients’ ratings of daytime sleepiness by use of the Epworth Sleepiness Scale (ESS): change from baseline and rate of patients with a post-baseline total score between 11 and 15 and > 15 (excessive daytime sleepiness)
- Time to dropout due to intolerability until Visit V26 (double-blind phase) and Visit V52 (open-label long-term phase) |
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| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | 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) | 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) | Yes |
| 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 | 6 |
| 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 | 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 | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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