Study of Parkinson's Early Stage With Deferiprone

Study Overview
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Brief Summary
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The goal of this study is to evaluate the effects of deferiprone, an iron-chelating drug, in patients with Parkinson's disease. Participants will be randomized to receive one of four different dosages of deferiprone or placebo, and will take the assigned study product twice a day for nine months.

Detailed Description
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This study will enroll 140 patients who have been diagnosed with Parkinson's disease within the last 3 years and are currently taking antiparkinsonian medication. There are four dosage cohorts, with patients in each cohort receiving either deferiprone tablets or placebo. At the baseline visit, participants will be randomized to a dosage cohort and to either active product or placebo within that cohort, and will take the assigned study product twice-daily for 9 months. They will come back to the study site for assessments at Months 1, 2, 3, 4, 5, 6, and 9, and will need to have their blood count checked weekly, at either the study site or a local laboratory.

Official Title
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A Dose-Ranging Study of the Efficacy, Safety, and Pharmacokinetics of Deferiprone Delayed Release Tablets in Patients With Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Deferiprone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥18 to < 80 years Body weight ≥60 kg but ≤100 kg Parkinson's disease diagnosed Absolute neutrophil count (ANC) ≥1.5 x 10^9/L (≥1.0 x 10^9/L for Black population) at screening On a stable dose for at least 3 months prior to the screening visit of any of the following treatments at an L-dopa equivalent daily dose of up to 600 mg: Dopaminergic agonist alone L-dopa alone Combination therapy with dopaminergic agonist and L-dopa Rasagiline At an early stage of the disease, without motor fluctuations and/or L-dopa-induced dyskinesia Exclusion Criteria: Diagnosis of Parkinson's disease more than 3 years prior to screening visit Hoehn and Yahr stage ≥ 3 Atypical or secondary Parkinsonism without dopa-sensitivity (e.g., vascular parkinsonism, supranuclear palsy, multisystem atrophy) Progressing Axis I psychiatric disorders (psychosis, hallucinations, compulsive disorders, substance addiction, bipolar disorder, severe depression, anxiety) as assessed in a semi-structured interview in accordance with the Diagnostic and Statistical Manual of Mental Disorders Not stabilized in terms of the current antiparkinsonian therapeutic regimen: already requires dose adaptation and/or is likely to require any change in dopamine therapy over the duration of the trial Current treatment with bromocriptine Current treatment with any antiparkinsonian drug other than those listed in the inclusion criteria Current treatment with coenzyme Q10 or idebenone. (Patients who are on these medications but stop taking them at least 2 weeks prior to baseline may be enrolled.) Current use of a Deep Brain Stimulation (DBS) system. (Patients who previously had a DBS system but have had it removed may be enrolled.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferiprone 300 mg<br>One-half of a 600 mg tablet of deferiprone twice a day, for a total daily dosage of 600 mg | Drug: Deferiprone<br>* 600 mg tablets<br>* Other names: DFP;|
| Experimental: Deferiprone 600 mg<br>One 600 mg tablet of deferiprone twice a day, for a total daily dosage of 1200 mg | Drug: Deferiprone<br>* 600 mg tablets<br>* Other names: DFP;|
| Experimental: Deferiprone 900 mg<br>One and a half 600 mg tablets of deferiprone twice a day, for a total daily dosage of 1800 mg | Drug: Deferiprone<br>* 600 mg tablets<br>* Other names: DFP;|
| Experimental: Deferiprone 1200 mg<br>Two 600 mg tablets of deferiprone twice a day, for a total daily dosage of 2400 mg | Drug: Deferiprone<br>* 600 mg tablets<br>* Other names: DFP;|
| Placebo Comparator: Placebo<br>Depending on dosage cohort, either one half-tablet, one tablet, one and a half tablets, or two tablets of placebo, twice a day | Drug: Placebo<br>* Tablets that match the deferiprone tablets in appearance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on the Part III subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | Change from baseline to Month 9 in motor examination, as assessed by score on Part III of the MDS-UPDRS | Nine months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total score on the MDS-UPDRS | Change from baseline to Month 9 in total score on the MDS-UPDRS | Nine months | 
| Scores on the Part I, Part II, and Part IV subscales of the MDS-UPDRS | Change from baseline to Month 9 in non-motor experiences of daily living, motor experiences of daily living, and motor complications, as assessed by scores on Parts I, II, and IV, respectively of the MDS-UPDRS | Nine months | 
| Combined scores from Parts II and III of the MDS-UPDRS | Change from baseline to Month 9 in combined scores from Parts II and III of the MDS-UPDRS | Nine months | 
| Score on the Montreal Cognitive Assessment (MoCA) test | Change from baseline to Month 9 in overall cognitive function as assessed by MoCA score | Nine months | 
| Pharmacodynamics measures of oxidative stress biomarkers | Change from baseline to Month 9 in oxidative stress | Nine months | 
| Pharmacodynamics measures of inflammatory factor biomarkers | Change from baseline to Month 9 in inflammatory factor | Nine months | 
| Time until need for rescue medication | Time elapsed until the patient is deemed to require a change or increase in antiparkinsonian medication | Up to nine months | 
| Safety of deferiprone | Number of subjects with adverse events | Nine months | 
| Cmax for serum deferiprone and deferiprone 3-O-glucuronide | Maximum measured serum concentration. Blood samples collected at baseline and Month 3, pre-dose and at 2 hours and 4 hours post-dose. | 4 hours | 
| Tmax for serum deferiprone and deferiprone 3-O-glucuronide | Time to maximum observed serum concentration. Blood samples collected at baseline and Month 3, pre-dose and at 2 hours and 4 hours post-dose. | 4 hours | 
| AUC0-∞for Serum Deferiprone and Deferiprone 3-O-glucuronide | Area under the serum concentration time curve extrapolated to infinity. Blood samples collected at baseline and Month 3, pre-dose and at 2 hours and 4 hours post-dose. | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Deferiprone