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

NCT ID: NCT03881371

Last Updated: 2024-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 307 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2021-08-20

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).

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Safinamide

Intervention Type: DRUG

At baseline (Day 1), eligible patients will be randomised to receive safinamide (initial 50 mg titrated to 100 mg the day after the Visit 3/week 2, ideally at day 15). The investigational medicinal product (IMP) will be taken in the morning at breakfast time, in addition to the morning dose of L-dopa and other (if any) PD medications.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

At baseline (Day 1), eligible patients will be randomised to receive matching placebo, orally OD. 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

Interventions

Safinamide

At baseline (Day 1), eligible patients will be randomised to receive safinamide (initial 50 mg titrated to 100 mg the day after the Visit 3/week 2, ideally at day 15). The investigational medicinal product (IMP) will be taken in the morning at breakfast time, in addition to the morning dose of L-dopa and other (if any) PD medications.

Intervention Type: DRUG

Placebo

At baseline (Day 1), eligible patients will be randomised to receive matching placebo, orally OD. 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

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zambon SpA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sir Run Run Shaw Hospital, Zhejiang University 浙江大学医学院附属邵逸夫医院

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

Shanghai, No 639, Zhizaoju Road, China

Tianjin Union Medicine Center 天津市人民医院

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

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

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

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

Chengdu, No. 37, Guoxue Alley, China

Beijing Friendship Hospital 首都医科大学附属北京友谊医院

Beijing, No. 6, Tiantan XI Li, Chongwen District, China

Beijing Tiantan Hospital Affiliated to Capital Medical University 首都医科大学附属北京天坛医院

Beijing, No. 6, Tiantan XI Li, Chongwen District, China

The First Bethune Hospital of Jilin University

Changchun, No. 71, Xin Min Street, China

The First Hospital of Shanxi Medical University 山西医科大学第一医院

Taiyuan, No. 85, Jie Fang South Road, China

The Second Affiliated Hospital of Zhejiang University 浙江大学医学院附属第二医院

Hangzhou, No. 88, Jie Fang Rd., China

The Second Affiliated Hospital of Nanchang University 南昌大学第二附属医院

Nanchang, No.1 Minde Road of Nanchang, China

Guangzhou First People's Hospital 广州市第一人民医院

Guangzhou, No.1 Panfu Rd., China

Shanghai General Hospital 上海市第一人民医院

Shanghai, No.100 Haining Road, China

Sun Yat-sen Memorial Hospital 中山大学孙逸仙纪念医院

Guangzhou, No.107, Yanjiang West Road, China

Tongji Hospital of Tongji University 同济大学附属同济医院

Wuhan, No.1095 Jiefang Avenue, China

The Third Hospital of Hebei Medical University 河北医科大学第三医院

Shijiazhuang, No.139.Zi Qiang Rd, China

Chongqing Three Gorges Central Hospital 重庆三峡中心医院

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

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

Baotou, No.41 Linyin Road, China

Baotou City Central Hospital 包头市中心医院

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

Xuzhou, No.99, Huaihai West Road, Xuzhou, Jiangsu, China

The Affiliated Hospital Of Guiyang Medical College 贵州医科大学附属医院

Guiyang, No28. Guiyi Street, China

The First Affiliated Hospital of Guangzhou Medical University 广州医科大学附属第一医院

Guangzhou, Number 151, Yanjiang Road, China

Wenzhou Medical College-The First Affiliated Hospital 温州医科大学附属第一医院

Wenzhou, Shangcai Burg, Ouhai District, China

Daqing Oilfield General Hospital 大庆油田总医院

Daqing, , China

Fujian Medical University Union Hospital 福建医科大学附属协和医院

Fuzhou, , China

Qilu Hospital of Shandong University 山东大学齐鲁医院

Jinan, , China

Nanjing Drum Tower Hospital 南京鼓楼医院

Nanjing, , China

The second affiliated hospital of Soochow University 苏州大学附属第二医院

Suzhou, , China

Countries

China

References

Dei Cas A, Micheli MM, Aldigeri R, Gardini S, Ferrari-Pellegrini F, Perini M, Messa G, Antonini M, Spigoni V, Cinquegrani G, Vazzana A, Moretti V, Caffarra P, Bonadonna RC. Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: a proof-of-concept clinical trial. J Endocrinol Invest. 2024 Sep;47(9):2339-2349. doi: 10.1007/s40618-024-02320-7. Epub 2024 Apr 2.

Reference Type: DERIVED

PMID: 38565814 (View on PubMed)

Cattaneo C, Kulisevsky J. The Effects of Safinamide in Chinese and Non-Chinese Patients with Parkinson's Disease. Adv Ther. 2024 Feb;41(2):638-648. doi: 10.1007/s12325-023-02736-2. Epub 2023 Dec 9.

Reference Type: DERIVED

PMID: 38070039 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36346534 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Z7219L05

Identifier Type: -

Identifier Source: org_study_id