A study to evaluate the efficacy of Rotigotine (the treatment) versus placebo in patients with pain associated with Parkinson's Disease

• Register: EUCTR
• Last refreshed on: 26 August 2013
• Main ID: EUCTR2012-002608-42-DE
• Date of registration: 26/09/2012
• Prospective Registration: Yes
• Primary sponsor: UCB Biosciences GmbH
• Public title: A study to evaluate the efficacy of Rotigotine (the treatment) versus placebo in patients with pain associated with Parkinson's Disease
• Scientific title: A Multicenter, Multinational, Double-blind, Placebo-controlled, 2-arm Study to Evaluate the Efficacy of Rotigotine on Parkinson's Disease-Associated Pain
• Date of first enrolment: 10/01/2013
• Target sample size: 64
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002608-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Germany, Hungary, Poland, Slovakia, United Kingdom, United States

Contacts

• Name: Sigrid Nilius
• Affiliation: UCB Biosciences GmbH

• Name: Sigrid Nilius
• Affiliation: UCB Biosciences GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject.
2. Subject is considered reliable and capable of adhering to the protocol, visit schedule, completion of the diary, and medication application according to the judgment of the investigator.
3. Subject is male or female and =18 years of age at the Screening Visit.
4. Subject has idiopathic Parkinson’s disease, defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: resting tremor, rigidity, or impairment of postural reflexes, and without any other known or suspected cause of Parkinsonism.
5. Subject is taking levodopa (either immediate or sustained release, in combination either with benserazide or carbidopa) with a stable daily dose of at least 200mg for at least 21 days prior to starting the documentation in the diary. The dose is expected to be maintained for the duration of the study.
6. Subject has a Hoehn and Yahr stage score of II to IV in the “on” state at the Screening Visit.
7. Subject is experiencing chronic pain associated with Parkinson’s disease for at least 3 months and of at least 4 points on an 11-point Likert Pain Scale (average pain experienced during last 7 days) at the Screening Visit. Pain characteristics with at least 1 kind of Parkinson’s disease pain to be included:
? Dystonia
? Musculoskeletal pain
? Central neuropathic pain
? Other pains worsened by Parkinson’s disease (except dyskinesia)
8. Subject has a Mini-Mental State Examination (MMSE) score =25 at the Screening Visit.
9. If the subject is taking a monoamine oxidase (MAO)-B inhibitor, an anticholinergic agent, the catechol-O-methyl transferase (COMT) inhibitor entacapone or the N-methyl-D aspartate (NMDA) antagonist amantadine, he/she must have been on a stable dose for at least 21 days prior to starting the documentation in the diary, and the dose is expected to be maintained for the duration of the study.
10. If the subject is taking an antidepressant drug such as a selective serotonin reuptake inhibitor, serotonin norepinephrine reuptake inhibitor, bupropion, or tricyclic antidepressants, he/she must have been on a stable dose for at least 21 days prior to starting the documentation in the diary, and the dose is expected to be maintained for the duration of the study.
11. Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and spermicide). Abstinence only is not an acceptable method. Subjects must agree to use adequate contraception during the study and for 4 weeks after their final dose of rotigotine (or longer, if required by local regulations).

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 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

Exclusion criteria:
1. Subject has previously participated in this study or subject has previously been assigned to treatment in a study of the medication under investigation in this study.
2. Subject has participated in another study of an investigational medicinal product (IMP) (or a medical device) within the last 28 days prior to the Screening Visit or is currently participating in another study of an IMP or a medical device.
3. Subject has had therapy with a dopamine agonist within 21 days prior to starting the documentation in the diary.
4. Subject discontinued from previous therapy with a dopamine agonist after an adequate length of treatment, at an adequate dose, due to lack of efficacy as assessed by the investigator.
5. Subject is receiving therapy with any of the following medications within 21 days prior to starting the documentation in the diary: dopamine modulating substances (eg, reserpine), dopamine releasing substances (eg, methylphenidate, amphetamine), alpha-methyldopa, metoclopramide, budipine, tolcapone, Duodopa®, neuroleptics (including atypical neuroleptics), MAO-A inhibitors, opioids, and opiates.
6. Subject is receiving analgesics for the treatment for pain, unless the dose has been stable for at least 21 days prior to starting the documentation in the diary and the dose is likely to remain stable for the duration of the study.
7. Subject has a history of chronic alcohol or drug abuse within the last 6 months.
8. Subject has any medical or psychiatric condition (eg, bipolar disorder, dementia, hallucinations, or psychosis) that, in the opinion of the investigator, could jeopardize or would compromise the subject’s ability to participate in this study.
9. Subject has a known hypersensitivity to any components of the IMP or comparative drugs as stated in the protocol.
10. Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response (“Yes”) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at the Screening Visit.
11. Subject has an atypical Parkinson’s disease syndrome due to drugs (eg, neuroleptics, metoclopramide, flunarizine), metabolic neurogenetic disorders (eg, Wilson Disease), encephalitis, cerebrovascular disease, or degenerative diseases (progressive supranuclear palsy).
12. Subject has a history of deep brain stimulation.
13. Subject has a significant skin disease that would make transdermal drug use inappropriate, including a history of skin sensitivity to adhesives or transdermal medications.
14. Subject has received electroconvulsive therapy within 12 weeks prior to the Screening Visit.
15. Subject has evidence of an Impulse Control Disorder (ICD) according to the modified Minnesota Impulse Disorders Inventory (mMIDI) at the Screening Visit confirmed by a positive structured clinical interview.
16. Subject has a previous diagnosis of severe restless legs syndrome.
17. Subject has chronic migraine (>15 days per month).
18. Subject currently has severe depression.
19. Subject is currently lactating or pregnant or planning to become pregnant during the duration of the study.
20. Subject has symptomatic orthostatic hypotension at the Screening Visit.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson’s disease
MedDRA version: 16.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Neupro
Product Name: Rotigotine
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: ROTIGOTINE
CAS Number: 99755-59-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 9-
Pharmaceutical form of the placebo: Transdermal patch
Route of administration of the placebo: Transdermal use

Trade Name: Neupro
Product Name: Rotigotine
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: ROTIGOTINE
CAS Number: 99755-59-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 13.5-

Trade Name: Neupro
Product Name: Rotigotine
Pharmaceutical Form: Transdermal patch
INN or Proposed INN: ROTIGOTINE
CAS Number: 99755-59-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Following titration (7 weeks) and maintainance (12 weeks) periods, 19 weeks total

Primary end point(s): Change from Baseline to the end of the Maintenance Period in pain severity “average pain experienced in the last 7 days” assessed by an 11-point Likert Pain Scale.

Secondary Objective: To investigate whether Rotigotine is effective on Parkinson’s disease associated chronic pain intensity and characterization, quality of life, depression, anxiety, and motor function in subjects with advanced-stage Parkinson’s disease.

Main Objective: To assess the effects of Rotigotine over placebo on improvement of Parkinson’s disease associated chronic pain in subjects with advanced-stage Parkinson’s disease experiencing Parkinson’s disease associated chronic pain.

Secondary Outcome(s)

Secondary end point(s): • Percentage of responders at the end of the Maintenance Period, with responders defined as "2-point or more reduction on an 11-point Likert Pain Scale"
• Change from Baseline to the end of the Maintenance Period in the sum score of the 8-item Parkinson’s Disease Questionnaire (PDQ-8)
• Change from Baseline to the end of the Maintenance Period of the 7-item depression subscore of the Hospital Anxiety and Depression Scale (HADS)
• Change from Baseline to the end of the Maintenance Period of the 7-item anxiety subscore of the HADS
• Change from Baseline to the end of the Maintenance Period in the combined score of the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II (Activities of Daily Living [ADL] subscale) and III (motor subscale)
• Change from Baseline to the end of the Maintenance Period in the 7 domain scores of classification of pain in Parkinson's disease

Timepoint(s) of evaluation of this end point: Following titration (7 weeks) and maintainance (12 weeks) periods, 19 weeks total

Secondary ID(s)

PD0004

Source(s) of Monetary Support

UCB Biosciences GmbH