Safinamide for Multiple System Atrophy (MSA)

NCT ID: NCT03753763

Last Updated: 2021-10-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-29
• Study Completion Date: 2021-01-05

Brief Summary

The study is a placebo controlled study, with two parallel arms, in which participants will be randomly assigned in a 2:1 ratio to receive either active (200 mg safinamide) or placebo in a double blind manner. Study population is patients diagnosed, with possible or probable parkinsonian variant of Multiple System Atrophy who are on a stable treatment of levodopa

Detailed Description

The overall design is a parallel group, placebo controlled, double blind study. The target population are participants diagnosed with possible or probable parkinsonian variant of Multiple System Atrophy who are on stable doses of levodopa.

Trial participation will be up to a maximum duration of 14 weeks and will comprise a screening period (up to 2 weeks), a 2-week run in period during which subjects will receive 1 tablet (either 100 mg safinamide or matching placebo), followed by a 10-week period, during which study participants will take 2 tablets of study medication (200 mg safinamide or placebo) once daily, taken in the morning in addition to their morning levodopa dose. A telephone follow-up call will be performed 2 weeks after the end of treatment.

Conditions

Multiple System Atrophy

Study Design

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

Study Groups

Active

Safinamide methanesulfonate film-coated tablets once daily

Group Type: EXPERIMENTAL

Safinamide Methanesulfonate

Intervention Type: DRUG

100 mg (free base)

Placebo

Safinamide Methanesulfonate matching placebo film-coated tablets once daily

Group Type: PLACEBO_COMPARATOR

Safinamide Methanesulfonate matching placebo

Intervention Type: DRUG

100 mg placebo

Interventions

Safinamide Methanesulfonate

100 mg (free base)

Intervention Type: DRUG

Safinamide Methanesulfonate matching placebo

100 mg placebo

Intervention Type: DRUG

Other Intervention Names

Xadago; placebo

Eligibility Criteria

Inclusion Criteria

1. Participant must be 30 to 80 years of age inclusive, at the time of signing the informed consent;

2. Participants who are diagnosed (with MRI confirmation) with possible or probable parkinsonian variant of Multiple System Atrophy less than 2 years ago;

3. Participants with an anticipated survival of at least 3 years in the opinion of the investigator;

4. Female not pregnant, not breastfeeding, and at least one of the following conditions applies:

• Not a woman of childbearing potential OR
• A woman of childbearing potential who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study intervention;

5. Capable of giving signed informed consent

Exclusion Criteria

1. History of neurosurgical procedure, including stereotactic surgery;

2. History of Deep Brain Stimulation (DBS);

3. History of bipolar disorder, severe depression, schizophrenia or other psychotic disorder;

4. History of drug and/or alcohol abuse within 12 months prior to screening as defined by the current edition of the Diagnostic and Statistical Manual of Mental Disorders;

5. History of dementia (DSM-V criteria);

6. 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;

7. Active hepatitis B or C;

8. History of human immunodeficiency virus (HIV) infection;

9. Subjects not able to swallow oral medications;

10. Subjects with severe orthostatic symptoms;

11. Impaired ambulation, i.e. falling more than once per week, bedridden patients or confined to a wheelchair during the whole day;

12. Subjects with active malignant neoplasms;

13. Movement disorders other than MSA (e.g. Parkinson Disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, pharmacological or post-encephalic parkinsonism);

14. Any clinically significant or unstable medical or surgical condition that, in the opinion of the investigator, might preclude safe completion of the study or might affect the results of the study;

15. Not on a stable regime, for at least 4 weeks prior to the randomization (baseline visit), of

1. oral levodopa (including controlled release, immediate release or a combination of controlled release/immediate release), with or without benserazide/carbidopa, with or without addition of a catechol O-methyltransferase (COMT) inhibitor or

2. dopamine agonist, anticholinergic and/or amantadine.

16. Patients should not have received treatment with monoamine oxidase inhibitors in the 2 weeks prior to the randomization visit, nor treatment with levodopa infusion, pethidine, opiates, opioids, fluoxetine, fluvoxamine in the 4 weeks prior to the randomization visit;

17. Patients should not have received treatment with an oral or depot neuroleptic within 12 weeks prior to the randomization visit;

18. Use of any investigational drug within 30 days prior to screening or 5 half-lives, whichever is the longest;

19. Montreal Cognitive Assessment (MoCA) ≤ 20;

20. Laboratory assessments showing moderate or severe hepatic impairment (2x ULN);

21. Allergy/sensitivity or contraindications to the investigational medicinal products (IMPs) or their excipients, anticonvulsants, levodopa or other anti-parkinsonian drugs;

22. Any clinically significant condition which, in the opinion of the Investigator, would not be compatible with study participation or represent a risk for patients while in the study.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zambon SpA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charlotte Keywood, MD

Role: STUDY_DIRECTOR

Zambon SpA

Locations

Università di Bologna

Bologna, , Italy

AAST degli Spedali Civili di Brescia

Brescia, , Italy

San Raffaele Cassino

Cassino, , Italy

Fondazione Università "G. D'Annunzio"

Chieti, , Italy

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli

Napoli, , Italy

Azienda Ospedaliera di Padova

Padua, , Italy

Azienda Opsedaliero Universitaria Pisana

Pisa, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio - Ruggi d'Aragona

Salerno, , Italy

Azienda Ospedaliera Santa Maria di Terni

Terni, , Italy

Hospital General Universitario de Elche

Alicante, , Spain

Hospital de Cruces

Barakaldo, , Spain

Hospital de la Santa Creu i Sant Pau Barcelona

Barcelona, , Spain

Hospital Universitario Gregorio Maranon

Madrid, , Spain

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitario Virgen de Rocio

Seville, , Spain

Countries

Italy; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-004145-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Z7219K01

Identifier Type: -

Identifier Source: org_study_id