An international trial of deferiprone in patients with Parkinson’s disease

A Dose-Ranging Study of the Efficacy, Safety, and Pharmacokinetics of Deferiprone Delayed Release Tablets in Patients with Parkinson’s Disease - LA48-0215

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-004344-19-GB

Enrollment

140

Registered

2016-02-16

Start date

2016-03-31

Completion date

Unknown

Last updated

2020-10-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson’s disease MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Interventions

Product Name: Deferiprone 600 mg delayed release tablet Pharmaceutical Form: Modified-release tablet INN or Proposed INN: DEFERIPRONE CAS Number: 30652-11-0 Concentration unit: mg milligram(s) Concent

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Male or female aged =18 to =65 years) yes F.1.3.1 Number of subjects for this age range 58

Exclusion criteria

Exclusion criteria: 1. Diagnosis of Parkinson’s disease more than 3 years prior to screening visit 2. Hoehn and Yahr stage = 3 3. Atypical or secondary Parkinsonism without dopa-sensitivity (e.g., vascular parkinsonism, supranuclear palsy, multisystem atrophy) 4. 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 5. 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 6. Current treatment with bromocriptine 7. Current treatment with any antiparkinsonian drug other than those listed in the inclusion criteria 8. 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.) 9. Current use of a Deep Brain Stimulation (DBS) system. (Patients who previously had a DBS system but have had it removed may be enrolled.)

Design outcomes

Primary

Measure	Time frame
Main Objective: Primary objective is to evaluate the efficacy of four different dosages of deferiprone delayed release (deferiprone-DR) tablets in patients with Parkinson’s disease.;Secondary Objective: Secondary objectives are: • To evaluate the safety and tolerability of deferiprone-DR tablets in patients with Parkinson’s disease • To evaluate the pharmacokinetics of deferiprone-DR tablets in a subset of study participants • To evaluate the relationship between the pharmacokinetics and pharmacodynamics of deferiprone-DR tablets Exploratory objectives are: • To determine whether the efficacy responses to deferiprone differ depending on the genotype of certain enzymes that are implicated in Parkinson’s disease • To determine whether the efficacy responses to deferiprone are correlated with ceruloplasmin levels or ceruloplasmin ferroxidase activities;Primary end point(s): Primary efficacy criterion: Change from baseline to Month 9 in the motor examination subscale (Part III) of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS);Timepoint(s) of evaluation of this end point: Efficacy assessments: • The MDS-UPDRS and MoCA will be completed at baseline and Months 3, 6, and 9 Note: The MDS-UPDRS and MoCA are to be administered early in the morning, at approximately the same time (± 1 hour) at each visit, and by the same qualified investigator.	—

Measure

Time frame

Main Objective: Primary objective is to evaluate the efficacy of four different dosages of deferiprone delayed release (deferiprone-DR) tablets in patients with Parkinson’s disease.;Secondary Objective: Secondary objectives are: • To evaluate the safety and tolerability of deferiprone-DR tablets in patients with Parkinson’s disease • To evaluate the pharmacokinetics of deferiprone-DR tablets in a subset of study participants • To evaluate the relationship between the pharmacokinetics and pharmacodynamics of deferiprone-DR tablets Exploratory objectives are: • To determine whether the efficacy responses to deferiprone differ depending on the genotype of certain enzymes that are implicated in Parkinson’s disease • To determine whether the efficacy responses to deferiprone are correlated with ceruloplasmin levels or ceruloplasmin ferroxidase activities;Primary end point(s): Primary efficacy criterion: Change from baseline to Month 9 in the motor examination subscale (Part III) of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS);Timepoint(s) of evaluation of this end point: Efficacy assessments: • The MDS-UPDRS and MoCA will be completed at baseline and Months 3, 6, and 9 Note: The MDS-UPDRS and MoCA are to be administered early in the morning, at approximately the same time (± 1 hour) at each visit, and by the same qualified investigator.

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Secondary

Measure	Time frame
Secondary end point(s): Secondary efficacy criteria: • Change from baseline to Month 9 in the following measures: - Total score on the MDS-UPDRS - Scores on the individual subscales Part I (non-motor experiences of daily living), Part II (motor experiences of daily living), and Part IV (motor complications) of the MDS-UPDRS - Combined scores from Parts II and III of the MDS-UPDRS - Overall cognitive function, as assessed by the Montreal Cognitive Assessment (MoCA) test - Pharmacodynamics measures of the following oxidative stress biomarkers: total antioxidant status, lipid peroxidation (malondialdehyde), protein carbonyls, 8-OHdG, glutathione, superoxide dismutase - Pharmacodynamics measures of the following inflammatory factor biomarkers: TNF alpha and IL-6 • Time elapsed until the need for rescue medication Exploratory efficacy criteria: Mechanism of action (MOA) biomarkers to evaluate the following: • Whether specific genotypes of the following enzymes which play a role in Parkinson’s disease affect the potential disease-modifying action of deferiprone: - D544E polymorphisms of the glycoprotein ceruloplasmin - V158M polymorphisms of the enzyme catechol O-methyltransferase (the only analysis will be determination at baseline of the COMT genotype) • Whether the degree of change from baseline in ceruloplasmin levels and ceruloplasmin ferroxidase activity is correlated with the efficacy of deferiprone Safety Criteria: • Adverse events (AEs): frequency, intensity, time to onset, duration, and relatedness to study drug • Serious adverse events (SAEs): frequency, intensity, time to onset, duration, and relatedness to study drug • Number of discontinuations due to AEs • Laboratory measures (hematology, blood chemistry, and urinalysis) • ECG • Vital signs • Physical examination • Assessment of suicidality (based on the Columbia Suicide Severity Rating Scale) Pharmacokinetics Criteria: The following PK parameters will be determined for deferiprone and it	—

Measure

Time frame

Secondary end point(s): Secondary efficacy criteria: • Change from baseline to Month 9 in the following measures: - Total score on the MDS-UPDRS - Scores on the individual subscales Part I (non-motor experiences of daily living), Part II (motor experiences of daily living), and Part IV (motor complications) of the MDS-UPDRS - Combined scores from Parts II and III of the MDS-UPDRS - Overall cognitive function, as assessed by the Montreal Cognitive Assessment (MoCA) test - Pharmacodynamics measures of the following oxidative stress biomarkers: total antioxidant status, lipid peroxidation (malondialdehyde), protein carbonyls, 8-OHdG, glutathione, superoxide dismutase - Pharmacodynamics measures of the following inflammatory factor biomarkers: TNF alpha and IL-6 • Time elapsed until the need for rescue medication Exploratory efficacy criteria: Mechanism of action (MOA) biomarkers to evaluate the following: • Whether specific genotypes of the following enzymes which play a role in Parkinson’s disease affect the potential disease-modifying action of deferiprone: - D544E polymorphisms of the glycoprotein ceruloplasmin - V158M polymorphisms of the enzyme catechol O-methyltransferase (the only analysis will be determination at baseline of the COMT genotype) • Whether the degree of change from baseline in ceruloplasmin levels and ceruloplasmin ferroxidase activity is correlated with the efficacy of deferiprone Safety Criteria: • Adverse events (AEs): frequency, intensity, time to onset, duration, and relatedness to study drug • Serious adverse events (SAEs): frequency, intensity, time to onset, duration, and relatedness to study drug • Number of discontinuations due to AEs • Laboratory measures (hematology, blood chemistry, and urinalysis) • ECG • Vital signs • Physical examination • Assessment of suicidality (based on the Columbia Suicide Severity Rating Scale) Pharmacokinetics Criteria: The following PK parameters will be determined for deferiprone and it

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Countries

Canada, France, Germany, United Kingdom

Contacts

Public ContactJohn Connelly

ApoPharma

jconnell@apopharma.com14164017296

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026