Status:Not yet recruiting
Keywords:Parkinson's , Apathy , Levodopa , Mood
The primary objective of this study is to assess the effects of rotigotine over placebo on improvement of non-motor feature apathy and motor symptoms in subjects with early-stage and advanced-stage idiopathic Parkinson's disease.
The secondary objectives of this study are to evaluate the change in quality of life, anhedonia, depressive symptoms, fatigue, cognitive impairment, apathy rated by the caregiver, and the safety and tolerability of rotigotine in subjects with early-stage and advanced-stage idiopathic Parkinson's disease with apathy.
To be eligible to participate in this study, all of the following criteria must be met:
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 or medication application according to the judgment of the investigator.
3. Subject is male or female and ≥18 years old 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 has unsatisfactory control of Parkinson’s disease motor symptoms under the current treatment, according to the judgment of the investigator.
6. Subject has a Hoehn and Yahr stage score of I to IV during the “on” state at the Screening Visit.
7. If subject is taking levodopa, he/she must be on a stable dose of levodopa (in combination with benserazide or carbidopa) for at least 28 days prior to the Baseline Visit, and the dose is expected to be maintained for the duration of the study.
8. Subject suffers from apathy associated with Parkinson’s disease for at least 3 months, evidenced by a score of ≥2 on UPDRS Part I Item 4 at the Screening Visit and an average of at least ≥14 on the AS at the Screening and Baseline Visit as rated by the subject.
9. Subject has a Mini-Mental State Examination (MMSE) score of ≥25 at the Screening Visit
(Subject's will be required to score > or equal to a 25 on the Mini-Mental State Examination (MMSE) at the screening visit. The MMSE evaluates the subject's level of cognitive functioning and can be used to monitor changes in subject's cognition during clinical studies. The MMSE consists of 11 questions and evaluates 6 areas of cognitive function: orientation, attention, immediate recall, short-term recall, language, and the ability to follow simple verbal and written commands. The MMSE is divided into 2 sections. The first section requires vocal responses to questions to test the subject's orientation, memory, and attention. The maximum score on this section is 21. In the second section, the subject is asked to follow verbal and written instructions. the maximum score for the section is 9. The total MMSE score that can be achieved is 30. Generally, scores of 20 or lower indicate some level of cognitive impairment.)
10. If the subject is receiving an anticholinergic agent, a monoamine oxidase (MAO) B-inhibitor, 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 28 days prior to the Baseline Visit, and the dose is expected to be maintained for the duration of the study.
11. If subject is taking an antidepressant drug, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, bupropion, or tricyclic antidepressants, he/she must have been on a stable dose for at least 28 days prior to the Baseline Visit, and the dose is expected to be maintained for the duration of the study.
12. 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).
Subjects are not permitted to enroll in the study if any of the following criteria are met:
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 prior therapy with a dopamine agonist within 28 days prior to the Baseline Visit.
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 has a history of chronic alcohol or drug abuse within the last 6 months.
6. Subject has any medical or psychiatric condition (ie, 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.
7. Subject has received neuroleptics (except clozapine and quetiapine), dopamine-releasing substances (eg, methylphenidate or amphetamine), dopamine-modulating substances (eg, reserpine), alpha-methyldopa, metoclopramide, MAO-A inhibitors, budipine, or tolcapone within 28 days of the Baseline Visit.
8. Subject has received electroconvulsive therapy within 12 weeks prior to the Screening Visit.
9. Subject is receiving current psychotherapy or behavior therapy while participating in this study.
10. Subject has a history of deep brain stimulation.
11. Subject has a known hypersensitivity to any components of the IMP or comparative drugs as stated in the protocol.
12. Subject has a significant skin disease that would make transdermal drug use inappropriate, including a history of skin sensitivity to adhesives or transdermal medications.
13. 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.
14. 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).
15. Subject has evidence of an impulse control disorder (ICD) according to the modified Minnesota Impulsive Disorders Interview (mMIDI) at the Screening Visit confirmed by a positive structured clinical interview.
16. Subject who is currently lactating or pregnant or planning to become pregnant during the duration of the study.
17. Subject diagnosed with severe depression as evidenced by a BDI-II score of ≥29 at the Screening Visit.
18. Subject has symptomatic orthostatic hypotension at Screening