Clinical trial NCT03881371: 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
Official title: A Randomised, Double-blind, Placebo-controlled 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Lead sponsor: Zambon SpA
Sponsor class: INDUSTRY
First posted: 2019-03-19
Enrollment: 307
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: 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).


Eligibility criteria: Inclusion Criteria:

1. Male or female patients aged ≥18 years old.
2. Chinese ethnicity.
3. Able to understand and willing to provide written informed consent.
4. Able to maintain an accurate and complete 24-hour diary with the help of a caregiver.
5. Diagnosis of idiopathic Parkinson's Disease (IPD) using the United Kingdom Parkinson's Disease Society Brain Bank criteria of more than 3 years duration.
6. 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.
7. A Hoehn and Yahr stage between 1-4 inclusive during the "ON" phase.
8. Experiencing motor fluctuations with a minimum of 1.5 hours/day of "OFF" time during the day (excluding morning akinesia), based on historical data.
9. 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:

1. Any form of Parkinsonism other than IPD.
2. Diagnosis of chronic migraine (\>15 days per month) or cancer pain.
3. L-dopa infusion.
4. Hoehn and Yahr stage 5 during the "ON" phase.
5. If female, pregnancy or breast-feeding.
6. Neurosurgical intervention of PD or stereotactic brain surgery.
7. Severe peak dose or biphasic dyskinesia, unpredictable or widely swinging fluctuations.
8. 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.
9. Drug and/or alcohol abuse within 12 months prior to the screening visit.
10. History of dementia or severe cognitive dysfunction.
11. 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.
12. Allergy/sensitivity or contraindications to the investigational medicinal products (IMPs) or their excipients, to anticonvulsants or to anti-Parkinson drugs.
13. 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.
14. Moderate or severe liver failure using the Child-Pugh classification score, or human immunodeficiency virus (HIV) infection.
15. 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.
16. 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.

Primary outcomes:
measure: Change From Baseline to Week 16 in the Mean Total Daily "OFF" Time
timeFrame: At baseline and Week 16
Secondary outcomes:
measure: Change From Baseline to Week 16 in Pain Severity, as Assessed by an 11 Point Numerical Rating Scale (NRS)
timeFrame: At baseline and Week 16
measure: Change From Baseline to Week 16 in the Mean Total Daily "ON" Time
timeFrame: At baseline and Week 16
measure: Change From Baseline to Week 16 in the Mean Daily "ON" Time With no/Non Troublesome Dyskinesia
timeFrame: At baseline and Week 16
measure: Change From Baseline to Week 16 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score During the "ON" Phase
timeFrame: At baseline and Week 16
measure: Change From Baseline to Week 16 in the UPDRS Part II Activities of Daily Living (ADL) Score During the "ON" Phase
timeFrame: At baseline and Week 16
measure: Change From Baseline to Week 16 in the UPDRS Part III (Motor Function) Score During the "ON" Phase
timeFrame: At baseline and Week 16
measure: Clinical Global Impression of Severity (CGI-S) Score Assessed at Week 16
timeFrame: At week 16
measure: Clinical Global Impression of Change (CGI-C) Assessed at Week 16
timeFrame: At baseline and Week 16
measure: Change From Baseline to Week 16 in the Parkinson's Disease Questionnaire-39 Items (PDQ-39) Score
timeFrame: At baseline and Week 16
Other outcomes:
measure: Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE)
timeFrame: From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])
Locations:
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University 浙江大学医学院附属邵逸夫医院
state: No 3, Qing Chun East Road
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital 上海交通大学医学院附属第九人民医院
state: No 639, Zhizaoju Road
city: Tianjin
country: China
facility: Tianjin Union Medicine Center 天津市人民医院
state: No. 130, Jie Yuan Rd., Hong Qiao District
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University 中南大学湘雅三医院
state: No. 138, Tong Zi Po Road, He XI Yue Lu District
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University 武汉大学人民医院
state: No. 238, Jie Fang Road
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital 四川省医学科学院·四川省人民医院
state: No. 32 XI Er Duan, First Ring Road, Qing Yang District
city: Chengdu
country: China
facility: West China Hospital, Sichuan University 四川大学华西医院
state: No. 37, Guoxue Alley
city: Beijing
country: China
facility: Beijing Friendship Hospital 首都医科大学附属北京友谊医院
state: No. 6, Tiantan XI Li, Chongwen District
city: Beijing
country: China
facility: Beijing Tiantan Hospital Affiliated to Capital Medical University 首都医科大学附属北京天坛医院
state: No. 6, Tiantan XI Li, Chongwen District
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: No. 71, Xin Min Street
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University 山西医科大学第一医院
state: No. 85, Jie Fang South Road
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University 浙江大学医学院附属第二医院
state: No. 88, Jie Fang Rd.
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University 南昌大学第二附属医院
state: No.1 Minde Road Of Nanchang
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital 广州市第一人民医院
state: No.1 Panfu Rd.
city: Shanghai
country: China
facility: Shanghai General Hospital 上海市第一人民医院
state: No.100 Haining Road
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital 中山大学孙逸仙纪念医院
state: No.107, Yanjiang West Road
city: Wuhan
country: China
facility: Tongji Hospital of Tongji University 同济大学附属同济医院
state: No.1095 Jiefang Avenue
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University 河北医科大学第三医院
state: No.139.Zi Qiang Rd
city: Chongqing
country: China
facility: Chongqing Three Gorges Central Hospital 重庆三峡中心医院
state: No.165 Xincheng Rd, Wanzhou District
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital 上海交通大学医学院附属瑞金医院
state: No.197 Ruijin Er Road
city: Baotou
country: China
facility: 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
state: No.41 Linyin Road
city: Baotou
country: China
facility: Baotou City Central Hospital 包头市中心医院
state: No.61, Huancheng Road, Donghe District
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University 徐州医科大学附属医院
state: No.99, Huaihai West Road, Xuzhou, Jiangsu
city: Guiyang
country: China
facility: The Affiliated Hospital Of Guiyang Medical College 贵州医科大学附属医院
state: No28. Guiyi Street
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University 广州医科大学附属第一医院
state: Number 151, Yanjiang Road
city: Wenzhou
country: China
facility: Wenzhou Medical College-The First Affiliated Hospital 温州医科大学附属第一医院
state: Shangcai Burg, Ouhai District
city: Daqing
country: China
facility: Daqing Oilfield General Hospital 大庆油田总医院
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital 福建医科大学附属协和医院
city: Jinan
country: China
facility: Qilu Hospital of Shandong University 山东大学齐鲁医院
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital 南京鼓楼医院
city: Suzhou
country: China
facility: The second affiliated hospital of Soochow University 苏州大学附属第二医院
Study officials:
References:
citation: Wei Q, Tan Y, Xu P, Tao E, Lu Z, Pan X, Wang B, Liu C, Dong X, Tian Y, Sun X, Cattaneo C, Chen S, Shang H; XINDI Study Investigators Group. The XINDI Study: A Randomized Phase III Clinical Trial Evaluating the Efficacy and Safety of Safinamide as Add-On Therapy to Levodopa in Chinese Patients with Parkinson's Disease with Motor Fluctuations. CNS Drugs. 2022 Nov;36(11):1217-1227. doi: 10.1007/s40263-022-00958-6. Epub 2022 Nov 8.