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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00627640




Registration number
NCT00627640
Ethics application status
Date submitted
13/02/2008
Date registered
3/03/2008
Date last updated
29/03/2013

Titles & IDs
Public title
Safinamide in Idiopathic Parkinson's Disease (IPD) With Motor Fluctuations, as add-on to Levodopa
Scientific title
A Phase III, Double-blind, Placebo-controlled, Randomised Trial to Determine the Efficacy and Safety of a Dose Range of 50 to 100 mg/Day of Safinamide, as add-on Therapy, in Subjects With Idiopathic Parkinson's Disease With Motor Fluctuations, Treated With a Stable Dose of Levodopa and Who May be Receiving Concomitant Treatment With Stable Doses of a Dopamine Agonist, an Anticholinergic and/or Amantadine
Secondary ID [1] 0 0
IND: 63,901
Secondary ID [2] 0 0
27919
Universal Trial Number (UTN)
Trial acronym
SETTLE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Parkinson's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Safinimide 50-100 mg/day
Treatment: Drugs - Matching Placebo

Experimental: 1 - 1 active (50 - 100 mg/day)

Placebo comparator: 2 -


Treatment: Drugs: Safinimide 50-100 mg/day
Safinamide, (S)-(+)-2-\[4-(3-fluorobenzyloxy) benzylamino\] propanamide methanesulfonate, is an a-aminoamide derivative

Treatment: Drugs: Matching Placebo
Matching Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Evaluate the change from baseline to W24 in daily "on" time ("on" time without dyskinesia plus "on" time with minor dyskinesia)
Timepoint [1] 0 0
24 weeks
Secondary outcome [1] 0 0
Evaluate the changes from baseline to W24 in Activities of Daily Living, cognition, dyskinesias, change in global clinical status, motor symptoms, motor fluctuations, change in levopoda dose and Health Related Quality of life
Timepoint [1] 0 0
24 weeks

Eligibility
Key inclusion criteria
Male and female between the ages of 30 to 80 years with diagnosis of idiopathic Parkinson's Disease of more than 5 years duration, with a Hoehn and Yahr stage of I-IV during an "off" phase.

Be levodopa-responsive and have been receiving treatment with a stable dose of levodopa for at least 4 weeks.

Have motor fluctuations, with >1.5 hours "off" time during the day. Be able to maintain an accurate and complete diary (18-hour)
Minimum age
30 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with medical conditions and/or taking concomitant medications that would have put them at risk, interfered with the study evaluations, or made them unable to complete the requirements of the study;.

Be in a late stage of Parkinson's Disease, and experiencing severe, disabling peak-dose or biphasic dyskinesia and/or unpredictable or widely swinging fluctuations in their symptoms.

Current diagnosis of substance abuse or history of alcohol or drug abuse in the past 3 months.

Have received treatment with safinamide previously. History of, or current depression psychosis (e.g. schizophrenia or psychotic depression) Evidence of dementia or cognitive dysfunction. History of allergic response to anticonvulsants, levodopa, or other anti-Parkinsonian agents.

Hypersensitivity or contraindications to MAO-B inhibitors. Ophthalmologic history including any of the following conditions: albino subjects, family history of hereditary retinal disease, progressive and/or severe diminution of visual acuity (i.e., 20/70), retinitis pigmentosa, retinal pigmentation due to any cause, any active retinopathy or ocular inflammation (uveitis), or diabetic retinopathy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2012
Sample size
Target
Accrual to date
Final
549
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Central Coast Neuroscience Research - East Gosford
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
- East Gosford
Recruitment outside Australia
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Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Newron Pharmaceuticals SPA
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Parkinson's Disease is a major neurodegenerative disorder in which there is a progressive loss of dopamine-containing neurons. The understanding that PD is a syndrome of dopamine (DA) deficiency led to the introduction in the clinical practice of L-dopa, a precursor of DA that crosses the blood brain barrier, and also to the use of selective inhibitors of MAO-B, the major DA metabolising enzyme in man.

Safinamide is an inhibitor of MAO-B. This is a phase III trial to evaluate the efficacy and safety of safinamide (50 and 100 mg p.o. q.a.m.) compared to placebo as add-on therapy to a stable dose to levodopa in subjects with advance idiopathic Parkinson's Disease.

The principal efficacy measure is the increase in mean daily "on" time during the 18-hr diary recording period.
Trial website
https://clinicaltrials.gov/study/NCT00627640
Trial related presentations / publications
Schapira AH, Fox SH, Hauser RA, Jankovic J, Jost WH, Kenney C, Kulisevsky J, Pahwa R, Poewe W, Anand R. Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol. 2017 Feb 1;74(2):216-224. doi: 10.1001/jamaneurol.2016.4467.
Public notes

Contacts
Principal investigator
Name 0 0
Algirdas Kakarieka, MD
Address 0 0
Merck Serono S.A., Geneva
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00627640