Clinical trial NCT04455555: Efficacy and Safety of Rotigotine in the Treatment of Patients With Early Stage of Primary Parkinson's Disease
Official title: Efficacy and Safety of Rotigotine in the Treatment of Patients With Early Stage of Primary Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease
Keywords: Parkinson's disease；rotigotine
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
First posted: 2020-07-02
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The efficacy and safety of rotigotine in the treatment of patients with early stage of primary Parkinson's disease

Detailed description: To evaluate the efficacy and safety of rotigotine sustained release microspheres therapy by injection in the treatment of patients with early stage of primary Parkinson's disease

Eligibility criteria: Inclusion Criteria:

* Subjects or their legal representatives understand and wish to participate in this clinical study and voluntarily sign the informed consent dated;
* In the investigator's judgment, believe that the subject or his legal representative is trustworthy and able to comply with the study protocol, visit plan, or receive the study drug treatment as required;
* During screening (interview 1) The subjects were older than 30 years old, regardless of gender;
* The subject had primary Parkinson's disease for 55 years and was diagnosed based on major signs such as delayed movement and at least one of the following symptoms: quiescence tremor, rigidity or postural reflexes, and no other known or suspected cause of Parkinson's disease;
* Hoehn-yahr stage 3 in the "open" state (excluding phase 0);
* Brief mental State examination (MMSE) ≥ 25;
* At baseline (visit 2), the exercise score (Part III) of the Unified Parkinson's Disease Rating Scale (U PDRS) under the "open" condition was greater than or equal to 10;
* If the subjects are receiving anticholinergic drugs (such as benzalkonium tropic, benzene hai suo, diethyl promethazine, its organism and than pp board), monoamine oxidase B (MAO B) inhibitors, N - Methyl - d - aspartate (NMDA) antagonist (such as amantadine) treatment, must dose before baseline visit (2) is stable at least 28 days, and maintain the dose treatment during the study period;
* Childbearing age women (such as: no sterilization surgery or postmenopausal women is less than 1 year) or male subjects agreed to during the entire study (screening visit to the end of the study) and reliable contraceptive measures (birth control pills, use a condom, abstinence, etc.), and the screening visit (l) and the baseline visit (2), the childbearing age women of pregnancy test results were negative.

Exclusion Criteria:

* A history of globulin resection, thalamic destruction, deep brain stimulation or fetal tissue transplantation;
* Dementia, active mental illness or hallucinations, major depression
* Those who received dopamine agonist within 28 days before baseline (visit 2);
* Those who received levodopa preparations (including levodopa compound preparations) within 28 days before baseline (visit 2), or those who received levodopa preparations for more than 6 months after diagnosis; Patients who received any of the following drugs: amphetamine or alpha within 28 days prior to baseline (visit 2)
* Receiving Central nervous system active drug therapy (e.g., tranquilizers, sleeping pills, antidepressants, antianxiety medications), except for those who have been on a stable dose for at least 28 days prior to baseline (visit 2) and are likely to remain stable during the study period;
* Atypical Parkinson's disease symptoms caused by the use of drugs (e.g., metoclopramide, flunarizine), hereditary metabolic diseases of the nervous system (e.g., Wilson's disease), encephalitis, cerebrovascular diseases, or degenerative diseases (e.g., progressive supranuclear palsy);
* Patients with a history of epilepsy, or with a history of stroke or transient ischemic stroke within 1 year before the visit;
* Intolerance or allergy to antiemetic drugs such as domperidone, ondansetron, tropisetron, granisetron;
* Patients with clinically significant liver function abnormalities are defined as 1.5 times of the upper limit of the reference range of total bilirubin \> or 2 times of the upper limit of the reference range of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>;
* Abnormal renal function with clinical significance (serum creatinine \> 2.0 mg/dL);
* Uncontrolled or significant cardiovascular disease, including New York Heart Association grade 2 or above congestive heart failure, unstable angina, myocardial infarction, or arrhythmias requiring treatment at screening (visit 1) in the 6 months prior to first administration of the study drug;
* During screening (interview I);
* A history of symptomatic postural hypotension; Systolic blood pressure reduction greater than or equal to 20 MMHG or diastolic blood pressure reduction greater than or equal to 10 mmHg during screening (visit l) and baseline (visit 2) from baseline to upright position for 1 or 3 minutes; Or patients with horizontal systolic blood pressure \< 105 mmHg during screening (visit I) and baseline (visit 2);
* Subjects with evidence of impulse control disorder (ICD) during screening (interview L);
* A history of suicide attempt (including actual attempt, interruption of attempt or failure of attempt) or suicidal ideation in the past 6 months, defined as "yes" to question 4 or 5 on the Columbine Suicide Severity Rating Scale (C-SSRS) at screening (interview L); those
* Patients with a history of narcolepsy;
* Screening (interview L) For those who had a history of alcohol abuse, drug abuse or drug addiction in the first 5 years, alcoholism was defined as drinking more than 14 units of alcohol per week (1 unit = 360 ml beer or 45 ml spirits with 40% alcohol or 150 ml wine);
* Screening for malignant tumors within 5 years before surgery, except adequately treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, local prostate cancer after radical surgery, and intraductal carcinoma in situ of the breast;
* Women during pregnancy or lactation;
* Previous participants in the Rotigotine trial were intolerant or had poor efficacy;
* Allergic to or known to be allergic to rotigotine or rotigotine microsphere preparations;
* Those who have participated in other drug clinical trials within 3 months prior to screening;
* Any other medical condition, mental condition, or laboratory abnormality of clinical significance that the investigator determines may interfere with the subject's ability to participate in the study.

Primary outcomes:
measure: Changes in the total Unified Parkinson Disease Rating Scale (UPDRS) (II +III) score
timeFrame: 32 weeks after treatment
Secondary outcomes:
measure: Unified Parkinson Disease Rating Scale (UPDRS) maximum table (II +III) total score
timeFrame: 32 weeks after treatment
measure: changes in part II of the Unified Parkinson Disease Rating Scale relative to baseline
timeFrame: 32 weeks after treatment
measure: changes in the severity (SI) score;
timeFrame: 32 weeks after treatment
measure: Changes in pd Questionnaire (PDQ-8) scores
timeFrame: 32 weeks after treatment
measure: Changes in pd sleep Disorders Scale (PDSS) score
timeFrame: 32 weeks after treatment
measure: Changes in Beck Depression Inventory II (BDI-II) scores
timeFrame: 32 weeks after treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
Study officials:
affiliation: Peking University Third Hospital
name: Dongsheng Fan, MD.PHD
role: PRINCIPAL_INVESTIGATOR
References: