Study of Parkinson's Early Stage With Deferiprone (SKY)

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Deferiprone; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Toronto Western Hospital
• France
  • Bordeaux, France
    • CHU de Bordeaux, Centre Expert Parkinson
  • Creteil, France
    • Hôpital Henri Mondor
  • Lille, France
    • Centre Hospitalier Régional Universitaire de Lille, Hôpital Roger Salengro
  • Limoges, France
    • Chu Dupuytren
  • Lyon, France
    • Hôpital Neurologique Pierre Wertheimer
  • Montpellier, France
    • CHRU de Montpellier - Hôpital Gui de Chauliac
  • Rennes, France
    • CHU Pontchaillou
  • Rouen, France
    • CHU Charles Nicoll - Rouen
  • Strasbourg, France
    • Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre
  • Toulouse, France
    • CHU Purpan, Hôpital Pierre Paul Riquet
• Germany
  • Dusseldorf, Germany
    • Heinriche-Heine Universität Düsseldorf
  • Kiel, Germany
    • UKSH Campus Kiel, Neurologie
  • Marburg, Germany
    • Universitätsklinikum Giessen und Marburg GmbH
  • Munich, Germany
    • Klinikum rechts der Isar
• United Kingdom
  • Bury, United Kingdom
    • Fairfield General Hospital
  • London, United Kingdom
    • Charing Cross Hospital
  • Newcastle Upon Tyne, United Kingdom
    • Newcastle Clinical Ageing Research Unit
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Devon
    • Exeter, Devon, United Kingdom
      • Royal Devon & Exeter Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferiprone 300 mg; One-half of a 600 mg tablet of deferiprone twice a day, for a total daily dosage of 600 mg	Drug: Deferiprone; 600 mg tablets; Other Names: DFP
Experimental: Deferiprone 600 mg; One 600 mg tablet of deferiprone twice a day, for a total daily dosage of 1200 mg	Drug: Deferiprone; 600 mg tablets; Other Names: DFP
Experimental: Deferiprone 900 mg; One and a half 600 mg tablets of deferiprone twice a day, for a total daily dosage of 1800 mg	Drug: Deferiprone; 600 mg tablets; Other Names: DFP
Experimental: Deferiprone 1200 mg; Two 600 mg tablets of deferiprone twice a day, for a total daily dosage of 2400 mg	Drug: Deferiprone; 600 mg tablets; Other Names: DFP
Placebo Comparator: Placebo; 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; Tablets that match the deferiprone tablets in appearance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 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 the score for the Part III subscale (motor examination) of the MDS-UPDRS. Scores on this subscale can range from 0 (best) to 132 (worst); hence, an increase would indicate progression of the disease and a decrease would indicate improvement. The change in score was calculated as least square means.	Nine months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Score on the MDS-UPDRS	Change from baseline to Month 9 in total score on the MDS-UPDRS. The total score can range from 0 (best) to 260 (worst); hence, an increase would indicate progression of the disease and a decrease would indicate improvement. The change in score was calculated as least square means.	Nine months
Change in Score on the Part I Subscale of the MDS-UPDRS	Change from baseline to Month 9 in the score for the Part I subscale (mentation, behavior, and mood) of the MDS-UPDRS. Scores on this subscale can range from 0 (best) to 52 (worst); hence, an increase would indicate progression of the disease and a decrease would indicate improvement. The change in score was calculated as least square means.	Nine months
Change in Score on the Part II Subscale of the MDS-UPDRS	Change from baseline to Month 9 in the score for the Part II subscale (activities of daily living) of the MDS-UPDRS. Scores on this subscale can range from 0 (best) to 52 (worst); hence, an increase would indicate progression of the disease and a decrease would indicate improvement. The change in score was calculated as least square means.	Nine months
Change in Score in the Part IV Subscale of the MDS-UPDRS	Change from baseline to Month 9 in the score for the Part IV subscale (motor complications) of the MDS-UPDRS. Scores on this subscale can range from 0 (best) to 24 (worst); hence, an increase would indicate progression of the disease and a decrease would indicate improvement. The change in score was calculated as least square means.	Nine months
Change in the Combined Scores From Parts II and III of the MDS-UPDRS	Change from baseline to Month 9 in the combined score for the Part II subscale (motor experiences of daily living) and the Part III subscale (motor examination) of the MDS-UPDRS. The scales for these two parts range from 0 (best) to 52 (worst) and from 0 (best) to 132 (worst), respectively. Hence, the combined score can range from 0 (best) to 184 (worst), and an increase would indicate progression of the disease and a decrease would indicate improvement. The change in score is presented as least square means.	Nine months
Change in Score on the Montreal Cognitive Assessment (MoCA) Test	Change from baseline to Month 9 in the score for overall cognitive function as assessed by the MoCA. The total score on the MoCA can range from 0 (worst) to 30 (best). Hence, a decrease in score would indicate progression of the disease and an increase would indicate improvement. The change in score is presented as least square means.	Nine months
Safety of Deferiprone	Number of subjects with adverse events	Nine months
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	Blood samples for pharmacokinetics assessments were collected at baseline, and at pre-dose and specified time points up to 12 hours post-dose at the Month 3 visit. The maximum measured serum concentration (Cmax) at the Month 3 visit was determined for deferiprone and its main metabolite, deferiprone 3-O-glucuronide.	4 hours
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	Blood samples for pharmacokinetics assessments were collected at baseline, and at pre-dose and specified time points up to 12 hours post-dose at the Month 3 visit. The time to maximum observed serum concentration (Tmax) at the Month 3 visit was determined for deferiprone and its main metabolite, deferiprone 3-O-glucuronide.	4 hours
Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide	Blood samples for pharmacokinetics assessments were collected at baseline, and at pre-dose and specified time points up to 12 hours post-dose at the Month 3 visit. The total drug exposure, AUC0-∞ (area under the serum concentration time curve extrapolated to infinity) at the Month 3 visit was determined for deferiprone and its main metabolite, deferiprone 3-O-glucuronide.	4 hours

Collaborators and Investigators

• Sponsor: ApoPharma
• Investigators: Principal Investigator: David Devos, MD, Hospitalier Régional Universitaire de Lille

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2016
• Primary Completion (Actual): August 2, 2019
• Study Completion (Actual): September 4, 2019

Study Registration Dates

• First Submitted: March 31, 2016
• First Submitted That Met QC Criteria: March 31, 2016
• First Posted (Estimated): April 5, 2016

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Parkinson's disease; Deferiprone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferiprone
• Other Study ID Numbers: LA48-0215

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO