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NCT Number: 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

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).

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Key information

Conditions

Parkinson Disease Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Movement Disorders Nervous System Diseases Neurodegenerative Diseases Parkinsonian Disorders Synucleinopathies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

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

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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;
  • 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.

Treatment and study plan

Safinamide

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

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

Primary outcomes

  1. Change From Baseline to Week 16 in the Mean Total Daily "OFF" Time

    Time frame: 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 outcomes

  1. Change From Baseline to Week 16 in Pain Severity, as Assessed by an 11 Point Numerical Rating Scale (NRS)

    Time frame: 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").

  2. Change From Baseline to Week 16 in the Mean Total Daily "ON" Time

    Time frame: 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).

  3. Change From Baseline to Week 16 in the Mean Daily "ON" Time With no/Non Troublesome Dyskinesia

    Time frame: 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).

  4. Change From Baseline to Week 16 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score During the "ON" Phase

    Time frame: 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.

  5. Change From Baseline to Week 16 in the UPDRS Part II Activities of Daily Living (ADL) Score During the "ON" Phase

    Time frame: 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.

  6. Change From Baseline to Week 16 in the UPDRS Part III (Motor Function) Score During the "ON" Phase

    Time frame: 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.

  7. Clinical Global Impression of Severity (CGI-S) Score Assessed at Week 16

    Time frame: 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.

  8. Clinical Global Impression of Change (CGI-C) Assessed at Week 16

    Time frame: 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.

  9. Change From Baseline to Week 16 in the Parkinson's Disease Questionnaire-39 Items (PDQ-39) Score

    Time frame: 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).

Other outcomes

  1. Number of Patients With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Event (TESAE)

    Time frame: From baseline until follow-up visit (1 Week after the end of treatment [Up to 2 Years])

    Evaluation of the safety and tolerability of safinamide compared with placebo in Chinese PD patients with motor fluctuations.

Sponsors and collaborators

Lead sponsor

Zambon SpA

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Mar 19, 2019
Registry last updated
Mar 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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