A Study to Evaluate the Efficacy and Safety of Safinamide, as add-on Therapy, in Idiopathic Chinese Parkinson's Disease (PD) Patients With Motor Fluctuations Treated With Stable Doses of Levodopa

Phase 3

Completed

Conditions: Parkinson Disease

Interventions: Other: Placebo
Drug: Safinamide

Registration Number: NCT03881371

Lead Sponsor: Zambon SpA

Brief Summary: This is a Phase III, multicentre, randomised, double-blind, placebo-controlled study to evaluate the effects of 100 mg safinamide, administered orally once daily (OD), in Chinese Parkinson's disease (PD) patients, experiencing motor fluctuations while on stable doses of Levodopa (L-dopa) (alone or in combination with other anti-Parkinson drugs). Eligible patients are required to meet the United Kingdom PD Society Brain Bank Clinical Diagnostic Criteria. The study involves a placebo group. Placebo will be added to the standard stabilized treatment as a control of the safinamide group, hence patients on placebo will have benefit from other ongoing anti-PD medication. A total of 306 patients will be randomised into this study (153 in the safinamide and 153 in the placebo groups).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 307

Inclusion Criteria

Male or female patients aged ≥18 years old.
Chinese ethnicity.
Able to understand and willing to provide written informed consent.
Able to maintain an accurate and complete 24-hour diary with the help of a caregiver.
Diagnosis of idiopathic Parkinson's Disease (IPD) using the United Kingdom Parkinson's Disease Society Brain Bank criteria of more than 3 years duration.
Be levodopa responsive and receiving treatment with stable daily doses of oral L-dopa, with or without benserazide/carbidopa, with or without addition of a catechol-O-methyltransferase (COMT) inhibitor and may be receiving concomitant treatment with stable doses of dopamine agonists, anticholinergics and/or amantadine for at least 4 weeks prior to the screening visit.
A Hoehn and Yahr stage between 1-4 inclusive during the "ON" phase.
Experiencing motor fluctuations with a minimum of 1.5 hours/day of "OFF" time during the day (excluding morning akinesia), based on historical data.
If female, be post-menopausal for at least one year or have undergone hysterectomy or, if of child-bearing potential, must have a negative pregnancy test, must not be breast-feeding nor become pregnant during the study and must use adequate contraception for 1 month prior to randomisation and for up to 1 month after the last dose of study drug. Adequate contraception is defined as:
1. Hormonal oral, implantable, transdermal, or injectable contraceptives or a non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit;
2. a male sexual partner who agrees to use a male condom with spermicide or a sterile sexual partner . For all women of child-bearing potential, urine pregnancy test result at screening must be negative.

For all women of child-bearing potential, urine pregnancy test result at screening must be negative.

Exclusion Criteria

Any form of Parkinsonism other than IPD.
Diagnosis of chronic migraine (>15 days per month) or cancer pain.
L-dopa infusion.
Hoehn and Yahr stage 5 during the "ON" phase.
If female, pregnancy or breast-feeding.
Neurosurgical intervention of PD or stereotactic brain surgery.
Severe peak dose or biphasic dyskinesia, unpredictable or widely swinging fluctuations.
History of major depression or other clinically significant psychotic disorder which compromise the ability to provide the informed consent or to participate to the study.
Drug and/or alcohol abuse within 12 months prior to the screening visit.
History of dementia or severe cognitive dysfunction.
Use of any investigational drug or device within 30 days prior to screening or 5 half-lives, whichever is the longest, or during the study.
Allergy/sensitivity or contraindications to the investigational medicinal products (IMPs) or their excipients, to anticonvulsants or to anti-Parkinson drugs.
Any clinically significant condition (including laboratory values) which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for patients while in the study.
Moderate or severe liver failure using the Child-Pugh classification score, or human immunodeficiency virus (HIV) infection.
Treatment with monoamine oxidase inhibitors (MAOIs), pethidine, opiates, opioids, fluoxetine, fluvoxamine in the 4 weeks prior to the screening visit. These drugs are not allowed throughout the study and up 2 weeks after the last dose of study drug.
Ophthalmologic history including any of the following conditions: albinism, uveitis, retinitis pigmentosa, retinal degeneration, active retinopathy, severe progressive diabetic retinopathy, inherited retinopathy or family history of hereditary retinal disease.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patient will receive matching placebo orally at an initial dose of 50 mg once daily (OD) and then will be increased the day after the Visit 3/week 2 (ideally at day 15) to the final dose of 100 mg OD. Treatment will continue daily for a total of 16 weeks.
Safinamide	Safinamide	Patient will receive film-coated Safinamide tablets orally at an initial dose of 50 mg once daily (OD) and then will be increased the day after the Visit 3/week 2 (ideally at day 15) to the final dose of 100 mg OD. Treatment will continue daily for a total of 16 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 16 in the Mean Total Daily "OFF" Time	At baseline and Week 16	The mean total daily "OFF" time was assessed by 24-hour patient diary cards, of safinamide 100 mg/day compared to placebo, given as add-on therapy in PD patients with motor fluctuations on stable doses of L-dopa. Patients completed the daily diary by selecting one of the following five options for each 30-minute time period: * "OFF" (Stiffness, marked decrease in mobility, or immobility). * "ON" without dyskinesia (Good or practically normal mobility without dyskinesia). * "ON" with non-troublesome dyskinesia (With dyskinesia but it does not interfere with function/cause meaningful discomfort). * "ON" with troublesome dyskinesia (With dyskinesia which interferes with function/causes meaningful discomfort. Of note, these dyskinesia movements are different from the rhythmic "tremor" (a symptom of Parkinson's Disease itself). * Asleep (Time spent asleep).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 16 in Pain Severity, as Assessed by an 11 Point Numerical Rating Scale (NRS)	At baseline and Week 16	The pain severity, was assessed by an 11-point Numerical Rating Scale (NRS). The NRS is a segmented numeric version of the visual analogue scale (VAS) in which a patient selects a whole number that best reflects the intensity of his/her pain, ranging from '0' ("no pain") to '10' ("worst possible pain").
Change From Baseline to Week 16 in the Mean Total Daily "ON" Time	At baseline and Week 16	The mean total daily "ON" time, as assessed by 24-hour patient diary cards. Patients completed the daily diary by selecting one of the following five options for each 30-minute time period: * "OFF" (Stiffness, marked decrease in mobility, or immobility). * "ON" without dyskinesia (Good or practically normal mobility without dyskinesia). * "ON" with non-troublesome dyskinesia (With dyskinesia but it does not interfere with function/cause meaningful discomfort). * "ON" with troublesome dyskinesia (With dyskinesia which interferes with function/causes meaningful discomfort. Of note, these dyskinesia movements are different from the rhythmic "tremor" (a symptom of Parkinson's Disease itself). * Asleep (Time spent asleep).
Change From Baseline to Week 16 in the Mean Daily "ON" Time With no/Non Troublesome Dyskinesia	At baseline and Week 16	The mean daily "ON" time with no/non troublesome dyskinesia, as assessed by 24-hour patient diary cards. Patients completed the daily diary by selecting one of the following five options for each 30-minute time period: * "OFF" (Stiffness, marked decrease in mobility, or immobility). * "ON" without dyskinesia (Good or practically normal mobility without dyskinesia). * "ON" with non-troublesome dyskinesia (With dyskinesia but it does not interfere with function/cause meaningful discomfort). * "ON" with troublesome dyskinesia (With dyskinesia which interferes with function/causes meaningful discomfort. Of note, these dyskinesia movements are different from the rhythmic "tremor" (a symptom of Parkinson's Disease itself). * Asleep (Time spent asleep).
Clinical Global Impression of Change (CGI-C) Assessed at Week 16	At baseline and Week 16	The CGI-C scale measured the change in the patient's clinical status from baseline using a 7-point scale, ranging from 1 (very much improved) to 7 (very much worse), with a score of 4 indicating no change. The change from the patient's baseline condition is assessed by the Investigator at all post-baseline visits.
Change From Baseline to Week 16 in the Parkinson's Disease Questionnaire-39 Items (PDQ-39) Score	At baseline and Week 16	The PDQ-39 comprises 39 questions measuring eight dimensions of health: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication and bodily pain. Dimension scores are coded on a scale of 0 (perfect health as assessed by the measure) to 100 (worst health as assessed by the measure).
Change From Baseline to Week 16 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score During the "ON" Phase	At baseline and Week 16	The UPDRS comprises 3 parts that evaluates any complication of treatment: Part I: Evaluation of mentation or cognition, behavior and mood. Part II: Evaluation of the activities of daily life. Part III: Evaluation of motor function. Part IV: Evaluation of complications of therapy. The UPDRS performed by the Investigator with points assigned to each item in the scale based on the patient's response as well as observation and physical examination. Together Parts I-III contain 44 items, with each item scored on a 5-point scale. Part IV contains 11 questions with a scale ranging from 0 to 23. Thus, the final total score may range from 0 (no disability) to 199 (total disability). The UPDRS is the most commonly used scale in clinical studies to follow the longitudinal course of PD. Part I Evaluation of mentation or cognition, behavior and mood contains 4 items with each item scored on a 5 point scale, the scale ranging from 0 to 16.
Change From Baseline to Week 16 in the UPDRS Part II Activities of Daily Living (ADL) Score During the "ON" Phase	At baseline and Week 16	The UPDRS= Unified Parkinson's Disease Rating Scale; is the most commonly used scale in clinical studies to follow the longitudinal course of PD. It is divided in 4 sections, each of them with several items. The score of each item is 0-1 or 0-4 (the majority) where 0 is no symptom while the highest score means the most severe symptom. UPDRS part I: 4 items, score 0-16 (total); UPDRS part II: 13 items, score 0-52 (total); UPDRS part III: 14 items, score 0-108 (total) UPDRS part IV: it is dived in 3 sections. Section A=dyskinesias, 4 items, score 0-13 (total); section B=clinical fluctuations, 4 items, score 0-7 (total); section C=other complications, 3 items, score 0-3 (total). The total score of the UPDRS (meaning of all the 4 parts) is 0-199 where 0 means no symptoms, 199 the most severe symptoms.
Clinical Global Impression of Severity (CGI-S) Score Assessed at Week 16	At week 16	The CGI-S scale measures global severity of illness at a given point in time. It is rated on a 7-point Likert-type scale ranging from 1 (normal, not ill at all) to 7 (extremely severe). The CGI-S was assessed at all visits, starting at baseline.
Change From Baseline to Week 16 in the UPDRS Part III (Motor Function) Score During the "ON" Phase	At baseline and Week 16	The UPDRS= Unified Parkinson's Disease Rating Scale; is the most commonly used scale in clinical studies to follow the longitudinal course of PD. It is divided in 4 sections, each of them with several items. The score of each item is 0-1 or 0-4 (the majority) where 0 is no symptom while the highest score means the most severe symptom. UPDRS part I: 4 items, score 0-16 (total); UPDRS part II: 13 items, score 0-52 (total); UPDRS part III: 14 items, score 0-108 (total) UPDRS part IV: it is dived in 3 sections. Section A=dyskinesias, 4 items, score 0-13 (total); section B=clinical fluctuations, 4 items, score 0-7 (total); section C=other complications, 3 items, score 0-3 (total). The total score of the UPDRS (meaning of all the 4 parts) is 0-199 where 0 means no symptoms, 199 the most severe symptoms.

Trial Locations

Locations (31): Beijing Tiantan Hospital Affiliated to Capital Medical University 首都医科大学附属北京天坛医院
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Beijing, No. 6, Tiantan XI Li, Chongwen District, China
The First Bethune Hospital of Jilin University
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Changchun, No. 71, Xin Min Street, China
The Second Affiliated Hospital of Zhejiang University 浙江大学医学院附属第二医院
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Hangzhou, No. 88, Jie Fang Rd., China
Sir Run Run Shaw Hospital, Zhejiang University 浙江大学医学院附属邵逸夫医院
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Hangzhou, No 3, Qing Chun East Road, China
Shanghai Ninth People's Hospital 上海交通大学医学院附属第九人民医院
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Shanghai, No 639, Zhizaoju Road, China
Tianjin Union Medicine Center 天津市人民医院
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Tianjin, No. 130, Jie Yuan Rd., Hong Qiao District, China
The Third Xiangya Hospital of Central South University 中南大学湘雅三医院
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Changsha, No. 138, Tong Zi Po Road, He XI Yue Lu District, China
Renmin Hospital of Wuhan University 武汉大学人民医院
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Wuhan, No. 238, Jie Fang Road, China
Sichuan Provincial People's Hospital 四川省医学科学院·四川省人民医院
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Chengdu, No. 32 XI Er Duan, First Ring Road, Qing Yang District, China
West China Hospital, Sichuan University 四川大学华西医院
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Chengdu, No. 37, Guoxue Alley, China
Beijing Friendship Hospital 首都医科大学附属北京友谊医院
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Beijing, No. 6, Tiantan XI Li, Chongwen District, China
The First Hospital of Shanxi Medical University 山西医科大学第一医院
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Taiyuan, No. 85, Jie Fang South Road, China
The Second Affiliated Hospital of Nanchang University 南昌大学第二附属医院
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Nanchang, No.1 Minde Road Of Nanchang, China
Guangzhou First People's Hospital 广州市第一人民医院
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Guangzhou, No.1 Panfu Rd., China
Shanghai General Hospital 上海市第一人民医院
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Shanghai, No.100 Haining Road, China
Sun Yat-sen Memorial Hospital 中山大学孙逸仙纪念医院
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Guangzhou, No.107, Yanjiang West Road, China
Tongji Hospital of Tongji University 同济大学附属同济医院
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Wuhan, No.1095 Jiefang Avenue, China
The Third Hospital of Hebei Medical University 河北医科大学第三医院
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Shijiazhuang, No.139.Zi Qiang Rd, China
Chongqing Three Gorges Central Hospital 重庆三峡中心医院
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Chongqing, No.165 Xincheng Rd, Wanzhou District, China
Shanghai Ruijin Hospital 上海交通大学医学院附属瑞金医院
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Shanghai, No.197 Ruijin Er Road, China
The First Affiliated Hospital of Baotou Medical University 内蒙古科技大学包头医学院第一附属医院
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Baotou, No.41 Linyin Road, China
Baotou City Central Hospital 包头市中心医院
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Baotou, No.61, Huancheng Road, Donghe District, China
The Affiliated Hospital of Xuzhou Medical University 徐州医科大学附属医院
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Xuzhou, No.99, Huaihai West Road, Xuzhou, Jiangsu, China
The First Affiliated Hospital of Guangzhou Medical University 广州医科大学附属第一医院
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Guangzhou, Number 151, Yanjiang Road, China
The Affiliated Hospital Of Guiyang Medical College 贵州医科大学附属医院
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Guiyang, No28. Guiyi Street, China
Wenzhou Medical College-The First Affiliated Hospital 温州医科大学附属第一医院
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Wenzhou, Shangcai Burg, Ouhai District, China
Daqing Oilfield General Hospital 大庆油田总医院
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Daqing, China
Fujian Medical University Union Hospital 福建医科大学附属协和医院
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Fuzhou, China
Nanjing Drum Tower Hospital 南京鼓楼医院
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Nanjing, China
Qilu Hospital of Shandong University 山东大学齐鲁医院
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Jinan, China
The second affiliated hospital of Soochow University 苏州大学附属第二医院
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Suzhou, China