Study of Parkinson's Early Stage With Deferiprone
- Registration Number
- NCT02728843
- Lead Sponsor
- ApoPharma
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 140
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Depending on dosage cohort, either one half-tablet, one tablet, one and a half tablets, or two tablets of placebo, twice a day Deferiprone 300 mg Deferiprone One-half of a 600 mg tablet of deferiprone twice a day, for a total daily dosage of 600 mg Deferiprone 600 mg Deferiprone One 600 mg tablet of deferiprone twice a day, for a total daily dosage of 1200 mg Deferiprone 900 mg Deferiprone One and a half 600 mg tablets of deferiprone twice a day, for a total daily dosage of 1800 mg Deferiprone 1200 mg Deferiprone Two 600 mg tablets of deferiprone twice a day, for a total daily dosage of 2400 mg
- Primary Outcome Measures
Name Time Method Change in Score on the Part III Subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Nine months 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.
- Secondary Outcome Measures
Name Time Method Change in Score on the Part II Subscale of the MDS-UPDRS Nine months 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.
Change in the Combined Scores From Parts II and III of the MDS-UPDRS Nine months 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.
Change in Score in the Part IV Subscale of the MDS-UPDRS Nine months 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.
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide 4 hours 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.
Change in Total Score on the MDS-UPDRS Nine months 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.
Change in Score on the Part I Subscale of the MDS-UPDRS Nine months 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.
Change in Score on the Montreal Cognitive Assessment (MoCA) Test Nine months 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.
Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide 4 hours 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.
Safety of Deferiprone Nine months Number of subjects with adverse events
Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide 4 hours 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.
Trial Locations
- Locations (20)
CHU Charles Nicoll - Rouen
🇫🇷Rouen, France
Newcastle Clinical Ageing Research Unit
🇬🇧Newcastle Upon Tyne, United Kingdom
UKSH Campus Kiel, Neurologie
🇩🇪Kiel, Germany
CHU Pontchaillou
🇫🇷Rennes, France
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Klinikum rechts der Isar
🇩🇪Munich, Germany
CHU Dupuytren
🇫🇷Limoges, France
CHRU de Montpellier - Hôpital Gui de Chauliac
🇫🇷Montpellier, France
Fairfield General Hospital
🇬🇧Bury, United Kingdom
Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre
🇫🇷Strasbourg, France
Universitätsklinikum Gießen und Marburg GmbH
🇩🇪Marburg, Germany
Hôpital Neurologique Pierre Wertheimer
🇫🇷Lyon, France
CHU Purpan, Hôpital Pierre Paul Riquet
🇫🇷Toulouse, France
Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
CHU de Bordeaux, Centre Expert Parkinson
🇫🇷Bordeaux, France
Hôpital Henri Mondor
🇫🇷Creteil, France
Centre Hospitalier Régional Universitaire de Lille, Hôpital Roger Salengro
🇫🇷Lille, France
Heinriche-Heine Universität Düsseldorf
🇩🇪Dusseldorf, Germany
Royal Devon & Exeter Hospital
🇬🇧Exeter, Devon, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom