| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10058920 |
|
| 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 demonstrate efficacy of rotigotine against placebo in subjects with idiopathic RLS over a 6-month maintenance period |
|
| E.2.2 | Secondary objectives of the trial |
| to investigate the safety and tolerability of rotigotine |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Subject is informed and given ample time and opportunity to think about her/his
participation and has given her/his written informed consent.
2. Subject understands the investigational nature of the trial and is willing and able
to comply with the trial requirements. Subject is willing to accept that he/she
might be treated with placebo during the treatment period.
3. Subject is able to apply/remove the trial patches correctly and consistently.
4. Subject is male or female, and is ≥18 and ≤75 years of age.
5. Subject meets the diagnosis of idiopathic RLS based on the 4 cardinal clinical
features according to the IRLSSG:
a. An urge to move legs, usually accompanied or caused by uncomfortable and
unpleasant sensations in the legs (The urge to move can be present without
uncomfortable sensations. Arms or other body parts can also be affected.).
b. The urge to move or unpleasant sensations begin or worsen during periods
of rest or inactivity such as lying or sitting.
c. The urge to move or unpleasant sensations are partially or totally relieved by
movement, such as walking or stretching, at least as long as the activity
continues.
d. The urge to move or unpleasant sensations are worse in the evening or night
than during the day or only occur in the evening or night (When symptoms
are very severe, the worsening at night may not be noticeable but must have
been previously present.).
6. Subject has had an initial response to previous dopaminergic treatment for RLS or
has had no previous dopaminergic treatment (ie, de novo).
7. The subject’s body mass index is ≥18kg/m2 and ≤35kg/m2.
8. At Baseline (Visit 2), subject has a score of ≥15 on the IRLS (indicating moderate
to severe RLS).
9. At Baseline (Visit 2), subject scores ≥4 points on the CGI Item 1 assessment
(indicating at least moderately ill).
|
|
| E.4 | Principal exclusion criteria |
1. Subject has secondary RLS (eg, due to renal insufficiency [uremia], iron
deficiency
anemia, or rheumatoid arthritis).
2. Subject has secondary RLS associated with previous or concomitant therapy with
dopamine D2 receptor antagonists, butyrophenones, metoclopramide, atypical
antipsychotics (eg, olanzapine), tri- and tetra-cyclic antidepressants, mianserine,
lithium, or due to withdrawal from drugs such as anticonvulsants,
benzodiazepines, barbiturates, and other hypnotics.
3. Subject has a current history of sleep disturbances like sleep apnea syndrome,
narcolepsy, sleep attacks/sudden onset of sleep, or myoclonus epilepsy either
observed during polysomnography or evidenced by subject history.
4. Subject has additional clinically relevant concomitant diseases such as
polyneuropathy, akathisia, claudication, varicosis, muscle fasciculation, painful
legs and moving toes, or radiculopathy.
5. Subject has other central nervous system diseases such as Parkinson’s disease,
dementia, progressive supranuclear paresis, multisystem atrophy, Huntington’s
Chorea, amyotrophic lateral sclerosis, or Alzheimer’s disease.
6. Subject has a prior history of psychotic episodes.
7. Subject has a history of chronic alcohol or drug abuse within the last 12 months.
8. Subject has any medical or psychiatric condition, which in the opinion of the
investigator, can jeopardize or would compromise the subject’s ability to
participate in this trial.
9. Subject has clinically relevant cardiac dysfunction and/or arrhythmias (eg,
suspected conduction system dysregulations, second or third degree AV block,
complete left or right bundle branch block, sick-sinus-syndrome, New York Heart
Association Class III or IV congestive heart failure, or has had a myocardial
infarction within 12 months prior to Screening [Visit 1]).
10. Subject has clinically relevant venous or arterial peripheral vascular disease.
11. Subject has clinically relevant renal dysfunction (serum creatinine >2.0mg/dL)
12. Subject has clinically relevant hepatic dysfunction (total bilirubin >2.0mg/dL or
alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater
than 2 times the upper limit of the reference range).
13. Subject has a malignant neoplastic disease requiring therapy within 12 months
prior to Screening (Visit 1).
14. Subject is currently receiving treatment with any of the following drug classes:
neuroleptics, hypnotics, antidepressants, anxiolytic drugs, anticonvulsive
therapy, opioids, benzodiazepines, monoamine oxidase (MAO) inhibitors,
catechol-O-methyl-transferase (COMT) inhibitors, sedative antihistamines,
psychostimulates, or amphetamines. If subject has received such therapy, a
washout period of at least 7 days prior to Baseline (Visit 2) is required before
starting treatment in this trial.
15. Subject is pregnant, nursing, or is a woman of child-bearing potential who is not
surgically sterile, 2 years postmenopausal, or does not consistently use 2
combined effective methods of contraception (including at least 1 barrier
method), unless sexually abstinent.
16. Subject pursues shift work or performs other continuous non-disease-related life
conditions which do not allow regular sleep at night.
17. Subject has a QTc interval of ≥500ms at Visit 1, or has an average QTc interval
of ≥500ms at Baseline (Visit 2). The average is taken from 3 ECGs performed at
least 15 minutes apart. Bazett’s correction method must be used for the
correction of the QT interval.
18. At Screening (Visit 1) or Baseline (Visit 2), subject has symptomatic orthostatic
hypotension with a decrease of blood pressure (BP) from supine to standing
position of ≥20mmHg in systolic blood pressure (SBP) or of ≥10mmHg in
diastolic blood pressure (DBP) taken from the 5 minute supine, and 1 and/or 3
minute standing measurements at Visit 1 or Visit 2, or supine SBP <105mmHg at
Baseline (Visit 2).
19. Subject has had previous treatment with dopamine agonists within a period of
28 days prior to Baseline (Visit 2), or L-dopa within 7 days prior to Baseline
(Visit 2).
20. Subject has a medical history indicating intolerability to dopaminergic therapy (if
pre treated).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary variables:
Efficacy will be assessed by the absolute change from Baseline at the end of the Maintenance Period in the IRLS sum score and the CGI Item 1 (severity of illness) score.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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 | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 the date of the last visit of the last patient 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 | 8 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 8 |
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