A double-blind, placebo-controlled, parallel group, proof of concept trial to assess the tolerabiltiy, safety and efficacy of rotigotine nasal spray for the acute treatment of 'off' symptoms in subjects with advanced-stage, idiopathic Parkinson's disease
- Conditions
- advanced-stage, idiopathic Parkinson's diseaseMedDRA version: 8.1Level: LLTClassification code 10061536
- Registration Number
- EUCTR2005-004290-19-DE
- Lead Sponsor
- Schwarz Biosciences GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1. Subject is informed and has been given ample time and opportunity to think
about his/her participation and has given his/her written informed consent.
2. Subject is willing and able to comply with all trial requirements.
3. Subject is aged =30 years.
4. Subject has idiopathic Parkinson disease, of more than 3 years in duration, as
defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the
following: resting tremor, rigidity, impairment of postural reflexes, and without
any known or suspected cause of Parkinsonism.
5. The investigator must observe the subject in both the on” and off” state and
determines that the subject is Hoehn and Yahr stage II -IV in both the on”
and off” state.
6. Subject has a Mini Mental State Examination (MMSE) score of = 25.
7. Subject is expected to be on a stable dose of levodopa, either short-acting or
sustained release (in combination with benserazide or carbidopa) for at least 28
days prior to baseline (Visit 2) of at least 300mg/day, administered in at least 3
intakes.
8. Subject experiences end-of-dose off” episodes despite attempts to optimize
levodopa regimen.
9. Subject has a UPDRS Part III in off” state of at least 25 points.
10. If the subject is receiving a dopamine agonist, entacapone, an anticholinergic
agent (eg, benztropine, trihexyphenidyl, parsitan, procyclidine, biperiden), a
monoamine oxidase (MAO) - B inhibitor (eg, selegiline, rasagiline), or a N-methyl-
D-aspartate (NMDA) -antagonist (eg, amantadine), he/she is expected to be on
a stable dose for at least 28 days prior to baseline (Visit 2).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Subject has previously participated in this trial or was assigned to treatment with
rotigotine in a previous trial.
2. Subject has participated in another trial of an investigational drug (or a medical
device) within the last 30 days or is currently participating in another trial of an
investigational drug (or a medical device).
3. Subject has atypical Parkinson syndrome(s), symptomatic Parkinson syndrome(s)
due to drugs (eg metoclopramide, flunarizine), metabolic neurogenetic disorders
(eg, Wilson disease), encephalitis, cerebrovascular disease or neurodegenerative
disease (eg progressive supranuclear palsy).
4. Subject has a history of pallidotomy, thalamotomy, deep brain stimulation or fetal
tissue transplant.
5. Subject has dementia, active hallucinations or active or treated psychosis. If
subjects has hallucinations, he/she may participate if hallucinations are treated,
and no symptoms occurred during the last 28 days.
6. Subject is receiving therapy with any of the following drugs currently or has done
so within 3 months prior to the hospital admission visit (Visit 2): MAO-A inhibitors
(pargyline, phenelzine and tranylcypromine), tolcapone, budipine, reserpine or
alpha-methyldopa.
7. Subject is currently receiving CNS active therapy (eg, sedatives, hypnotics, anti-
depressants, anxiolytics, atypical neuroleptics), unless the dose has been stable
for at least 28 days prior to Visit 2 and is likely to remain stable until end of Visit 3.
8. Subject has a current diagnosis of epilepsy, a history of seizures as an adult, a
history of stroke or had a TIA within 1 year prior to Visit 1.
9. Subject has clinically relevant hepatic dysfunction (as defined as a total bilirubin
> 2.0mg/dL or ALT and/or AST greater than 2 times the upper limit of the
reference range at Visit 1).
10. Subject has clinically relevant renal dysfunction (serum creatinine > 2.0mg/dL
[>178µmol/L] at Visit 1).
11. Subject has clinically relevant cardiac dysfunction (any cardiac disorder which in
the opinion of the investigator would put the subject at risk of clinically relevant
arrhythmia) and/or myocardial infarction within 1 year prior to Visit 1.
12. Subject has a QTc interval of = 500ms at Visit 1 (the Bazett's correction must be
used for the correction of the QT interval).
13. Subject has symptoms of rhinitis or local disease or irritation of the nasal mucosa
at Visit 2 or Visit 3.
14. Subject has had intra-nasal treatment within 14 days prior to Visit 3.
15. Subject has a history of symptomatic orthostatic hypotension, or systolic blood
pressure less than 105mmHg at trial entry.
16. Subject has a history of chronic alcohol or drug abuse within the last 6 months.
17. Subject has a known or suspected hypersensitivity to any component of the
investigational product or other nasal spray products.
18. Subject is pregnant or nursing, or is of child bearing potential but (i) not
surgically sterile or (ii) not using adequate birth control methods (including a
highly effective method of birth control and at least 1 barrier method) or (iii) not
sexually abstinent or (iv) subject is not at least 2 years post-menopausal
19. Subject has any medical condition, psychiatric condition or laboratory abnormality
that, in the opinion of the investigator, could jeopardize or would compromise
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this trial is to assess the tolerability and safety of rotigotine nasal spray in subjects with advanced-stage idiopathic Parkinson’s disease. ;Secondary Objective: The secondary objective is to assess the efficacy of rotigotine nasal spray.;Primary end point(s): • Adverse events, as reported spontaneously by the subject or observed by the <br> investigator recorded during the trial.<br>• Changes in blood pressure and heart rate (with special emphasis on potential <br> orthostatic reactions), electrocardiograms, clinical laboratory values.<br>• Changes in physical and neurological examination from Visit 2 to the Safety Follow-<br> up Visit.<br>• Proportion of subjects who complete the trial.<br>
- Secondary Outcome Measures
Name Time Method