| 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 | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10058920 |
| E.1.2 | Term | Restless legs syndrome |
|
| 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 objective of this trial is to explore the practicability and tolerability of switching subjects overnight from ropinirole or pramipexole to rotigotine transdermal patch and its effect on symptoms in subjects with idiopathic restless legs syndrome. |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| 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.
3. Subject is male or female, aged ≥ 18 years.
4. 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.).
5. Subject has had an initial response to oral dopaminergic treatment for RLS and
is not satisfactorily controlled on pramipexole or ropinirole
6. Subject has been on treatment with either pramipexole (up to 0,54mg of
base/day respectively up to 0.75mg of salt/day) or ropinirole (up to 4mg/day)
for >/= 28 days prior to Baseline visit (current dose should be stable for a
minimum of 28 days and should be covered by the labeled total daily dose for
RLS).
7. The subject’s body mass index is ≥ 18kg/m2 and ≤ 35kg/m2.
|
|
| E.4 | Principal exclusion criteria |
1. Subject has shown symptoms of augmentation with the current dopaminergic
therapy with pramipexole or ropinirole.
2. Subject has secondary RLS (e.g., due to renal insufficiency [uremia], iron
deficiency anemia or low ferritin (Ferritin <30µg/l) or rheumatoid arthritis).
3. 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
(e.g. mirtazipin), SNRI (e.g. venlafaxin), mianserine, lithium, or due to
withdrawal from drugs such as anticonvulsants, benzodiazepines, barbiturates,
and other hypnotics.
4. Subject has a positive result in at least one module of the Jay Modified
Minnesota Impulsive Disorders Interview (mMIDI) (a formal ICD diagnosis is not
necessary) at Screening Visit (SCR).
5. 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.
6. Subject has additional clinically relevant concomitant diseases such as
polyneuropathy, akathisia, claudication, varicosis, painful legs and moving toes,
or radiculopathy.
7. Subject has other central nervous system diseases such as dementia,
progressive supranuclear paresis, multisystem atrophy, Huntington’s chorea,
amyotrophic lateral sclerosis, or Alzheimer’s disease.
8. Subject has a prior history of psychotic episodes.
9. Subject has a history of chronic alcohol or drug abuse within the last 12 months.
10. 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.
11. Subject has clinically relevant cardiac dysfunction and/or arrhythmias (e.g.,
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 (SCR).
12. Subject has clinically relevant venous or arterial peripheral vascular disease.
13. Subject has clinically relevant renal dysfunction (serum creatinine >2.0mg/dL).
14. 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).
15. Subject has a malignant neoplastic disease requiring therapy within 12 months
prior to Screening Visit (SCR).
16. Subject is currently receiving treatment with any of the following drug classes:
neuroleptics, hypnotics, 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 (BSL) is required before starting treatment in this
trial.
17. 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.
18. Subject pursues shift work or performs other continuous non-disease-related life
conditions which do not allow regular sleep at night.
19. Subject has a QTc interval of ≥500ms at Screening Visit (SCR), or has an
average QTc interval of ≥500ms at Baseline (BSL). Bazett’s correction method
must be used for the correction of the QT interval.
20. At Screening Visit (SCR) 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Practicability and Tolerability
• Investigators assessment of practicability (IAP)
• Tolerability of rotigotine as determined by the total number of subjects completing
the trial:
• from Baseline to Day 28 and to End of Treatment
• on their original treatment dose assignment from Baseline to Day 28 and to
End of Treatment
• with at least one (1) dose adjustment from Baseline to Day 28 and to End of
Treatment
• Global Rating of Tolerability by the subject
Safety
Measured variables and changes over the course of trial will be performed on the following assessments, as appropriate:
• Frequency and severity of adverse events (AEs), as reported spontaneously by
the subject or observed by the investigator
• Vital signs
• 12 –lead electrocardiograms (ECGs)
• Clinical laboratory values (hematology, serum chemistry, endocrine
parameters, and urinalysis)
• Physical and neurological examination findings
• Clinical Global Impression (CGI) Item 4
• Assessment of augmentation
• Subject’s rating of daytime sleepiness as measured by the Epworth Sleepiness
Scale (ESS)
• Changes in menstrual and sexual function
• Adhesiveness of the patch
• Application site assessment
Efficacy
Measured variables, changes from Baseline and responder/remitter analyses will be performed on the following assessments, as appropriate:
• International Restless Legs Scale (IRLS) sum score
• CGI (Item 1-3)
• RLS-6 Rating Scales
• Global rating of efficacy by the subject
Patient Treatment Preference, Satisfaction and Health outcomes variables
• Rating of treatment preference and satisfaction as assessed by the subject
• Change from Baseline in the RLS-QoL (Quality of Life) questionnaire
|
|
| 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 | 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Practicability and Tolerability |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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 | No |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| 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 | 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
|
| The end of the trial is defined as the date of 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 | |
| E.8.9.1 | In the Member State concerned months | 20 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 20 |
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