Parkinson's Disease
Conditions
Keywords
Parkinson's disease, Deferiprone
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.
Interventions
DRUGDeferiprone
600 mg tablets
DRUGPlacebo
Tablets that match the deferiprone tablets in appearance
Sponsors
ApoPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The placebo tablets had the same appearance as the deferiprone tablets, and within each dosing cohort, all participants took the same number of tablets at each dose.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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 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. |
| Safety of Deferiprone | Nine months | Number of subjects with adverse events |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada, France, Germany, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 300 mg Patients took 300 mg deferiprone twice daily, for a total daily dosage of 600 mg | 27 |
| 600 mg Patients took 600 mg deferiprone twice daily, for a total daily dosage of 1200 mg | 26 |
| 900 mg Patients took 900 mg deferiprone twice daily, for a total daily dosage of 1800 mg | 25 |
| 1200 mg Patients took 1200 mg deferiprone twice daily, for a total daily dosage of 2400 mg | 28 |
| Placebo Depending on which dosage cohort they were in, patients took a number of placebo tablets that matched the number of tablets taken by patients receiving active product | 27 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 3 | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 0 | 4 | 2 | 2 |
| Overall Study | Use of rescue medication | 0 | 2 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 600 mg | Placebo | Total | 1200 mg | 900 mg | 300 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 8.5 | 61.9 years STANDARD_DEVIATION 9.2 | 61.4 years STANDARD_DEVIATION 9 | 60.3 years STANDARD_DEVIATION 8.7 | 59.8 years STANDARD_DEVIATION 10.2 | 61.5 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 26 Participants | 129 Participants | 26 Participants | 25 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| MDS-UPDRS Part I | 5.7 units on a scale STANDARD_DEVIATION 3 | 5.0 units on a scale STANDARD_DEVIATION 3.1 | 5.6 units on a scale STANDARD_DEVIATION 3.2 | 5.3 units on a scale STANDARD_DEVIATION 2.4 | 5.9 units on a scale STANDARD_DEVIATION 3.4 | 6.2 units on a scale STANDARD_DEVIATION 4.1 |
| MDS-UPDRS Part II | 5.8 units on a scale STANDARD_DEVIATION 3.9 | 6.1 units on a scale STANDARD_DEVIATION 4 | 5.1 units on a scale STANDARD_DEVIATION 4 | 3.9 units on a scale STANDARD_DEVIATION 3.1 | 5.7 units on a scale STANDARD_DEVIATION 5 | 4.1 units on a scale STANDARD_DEVIATION 3.5 |
| MDS-UPDRS Part III | 19.4 units on a scale STANDARD_DEVIATION 10.4 | 16.3 units on a scale STANDARD_DEVIATION 9.1 | 17.6 units on a scale STANDARD_DEVIATION 8.8 | 15.1 units on a scale STANDARD_DEVIATION 8.5 | 18.1 units on a scale STANDARD_DEVIATION 7.8 | 19.1 units on a scale STANDARD_DEVIATION 7.8 |
| MDS-UPDRS Part II/Part III | 25.2 units on a scale STANDARD_DEVIATION 12.4 | 22.4 units on a scale STANDARD_DEVIATION 10.6 | 22.7 units on a scale STANDARD_DEVIATION 10.8 | 19.1 units on a scale STANDARD_DEVIATION 9.9 | 23.8 units on a scale STANDARD_DEVIATION 10.8 | 23.2 units on a scale STANDARD_DEVIATION 10.1 |
| MDS-UPDRS Part IV | 0.2 units on a scale STANDARD_DEVIATION 0.8 | 0.0 units on a scale STANDARD_DEVIATION 0.2 | 0.2 units on a scale STANDARD_DEVIATION 0.7 | 0.2 units on a scale STANDARD_DEVIATION 0.8 | 0.1 units on a scale STANDARD_DEVIATION 0.6 | 0.2 units on a scale STANDARD_DEVIATION 0.8 |
| MDS-UPDRS Total Score | 31.1 units on a scale STANDARD_DEVIATION 13.3 | 27.4 units on a scale STANDARD_DEVIATION 12.3 | 28.4 units on a scale STANDARD_DEVIATION 12.1 | 24.5 units on a scale STANDARD_DEVIATION 10.7 | 29.8 units on a scale STANDARD_DEVIATION 12.3 | 29.7 units on a scale STANDARD_DEVIATION 11.6 |
| Montreal Cognitive Assessment | 28.1 units on a scale STANDARD_DEVIATION 1.7 | 27.1 units on a scale STANDARD_DEVIATION 1.9 | 27.6 units on a scale STANDARD_DEVIATION 1.8 | 27.5 units on a scale STANDARD_DEVIATION 2 | 27.3 units on a scale STANDARD_DEVIATION 1.9 | 27.7 units on a scale STANDARD_DEVIATION 1.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 27 Participants | 130 Participants | 26 Participants | 25 Participants | 27 Participants |
| Region of Enrollment Canada | 0 participants | 1 participants | 3 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment France | 19 participants | 18 participants | 93 participants | 21 participants | 18 participants | 17 participants |
| Region of Enrollment Germany | 3 participants | 2 participants | 12 participants | 0 participants | 3 participants | 4 participants |
| Region of Enrollment United Kingdom | 4 participants | 6 participants | 25 participants | 6 participants | 3 participants | 6 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 43 Participants | 15 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 20 Participants | 21 Participants | 90 Participants | 13 Participants | 19 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 26 / 28 | 25 / 28 | 23 / 28 | 25 / 28 | 25 / 28 |
| serious Total, serious adverse events | 2 / 28 | 1 / 28 | 3 / 28 | 4 / 28 | 1 / 28 |
Outcome results
Primary
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.
Time frame: Nine months
Population: Intent-to-treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Score on the Part III Subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | 2.1 Score on a scale | Standard Error 1.4 |
| Deferiprone 300 mg | Change in Score on the Part III Subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | 4.2 Score on a scale | Standard Error 1.4 |
| Deferiprone 600 mg | Change in Score on the Part III Subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | -0.8 Score on a scale | Standard Error 1.5 |
| Deferiprone 900 mg | Change in Score on the Part III Subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | 3.9 Score on a scale | Standard Error 1.5 |
| Deferiprone 1200 mg | Change in Score on the Part III Subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) | 2.2 Score on a scale | Standard Error 1.4 |
p-value: >0.05ANCOVA
Secondary
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.
Time frame: 4 hours
Population: Pharmacokinetics population: Included all patients who had sufficient PK data to derive at least one PK parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 8.358 μg*h/mL | Standard Deviation 0.904 |
| Placebo | Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 39.057 μg*h/mL | Standard Deviation 7.82 |
| Deferiprone 300 mg | Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 16.292 μg*h/mL | — |
| Deferiprone 300 mg | Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 62.679 μg*h/mL | — |
| Deferiprone 600 mg | Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 20.606 μg*h/mL | Standard Deviation 8.742 |
| Deferiprone 600 mg | Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 121.128 μg*h/mL | Standard Deviation 43.727 |
| Deferiprone 900 mg | Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 147.397 μg*h/mL | Standard Deviation 6.502 |
| Deferiprone 900 mg | Area Under the Curve for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 26.328 μg*h/mL | Standard Deviation 5.693 |
Secondary
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.
Time frame: Nine months
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Score in the Part IV Subscale of the MDS-UPDRS | -0.1 Score on a scale | Standard Error 0.2 |
| Deferiprone 300 mg | Change in Score in the Part IV Subscale of the MDS-UPDRS | 0.2 Score on a scale | Standard Error 0.2 |
| Deferiprone 600 mg | Change in Score in the Part IV Subscale of the MDS-UPDRS | 0.3 Score on a scale | Standard Error 0.2 |
| Deferiprone 900 mg | Change in Score in the Part IV Subscale of the MDS-UPDRS | 0.2 Score on a scale | Standard Error 0.2 |
| Deferiprone 1200 mg | Change in Score in the Part IV Subscale of the MDS-UPDRS | 0.4 Score on a scale | Standard Error 0.2 |
p-value: >0.05ANCOVA
Secondary
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.
Time frame: Nine months
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Score on the Montreal Cognitive Assessment (MoCA) Test | 1.1 Score on a scale | Standard Error 0.3 |
| Deferiprone 300 mg | Change in Score on the Montreal Cognitive Assessment (MoCA) Test | 1.0 Score on a scale | Standard Error 0.3 |
| Deferiprone 600 mg | Change in Score on the Montreal Cognitive Assessment (MoCA) Test | 0.9 Score on a scale | Standard Error 0.3 |
| Deferiprone 900 mg | Change in Score on the Montreal Cognitive Assessment (MoCA) Test | 1.1 Score on a scale | Standard Error 0.3 |
| Deferiprone 1200 mg | Change in Score on the Montreal Cognitive Assessment (MoCA) Test | 1.4 Score on a scale | Standard Error 0.3 |
p-value: >0.05ANCOVA
Secondary
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.
Time frame: Nine months
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Score on the Part II Subscale of the MDS-UPDRS | 1.1 Score on a scale | Standard Error 0.6 |
| Deferiprone 300 mg | Change in Score on the Part II Subscale of the MDS-UPDRS | 2.2 Score on a scale | Standard Error 0.6 |
| Deferiprone 600 mg | Change in Score on the Part II Subscale of the MDS-UPDRS | 0.6 Score on a scale | Standard Error 0.6 |
| Deferiprone 900 mg | Change in Score on the Part II Subscale of the MDS-UPDRS | 2.1 Score on a scale | Standard Error 0.6 |
| Deferiprone 1200 mg | Change in Score on the Part II Subscale of the MDS-UPDRS | 1.8 Score on a scale | Standard Error 0.6 |
p-value: >0.05ANCOVA
Secondary
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.
Time frame: Nine months
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Score on the Part I Subscale of the MDS-UPDRS | 0.8 Score on a scale | Standard Error 0.7 |
| Deferiprone 300 mg | Change in Score on the Part I Subscale of the MDS-UPDRS | 1.0 Score on a scale | Standard Error 0.7 |
| Deferiprone 600 mg | Change in Score on the Part I Subscale of the MDS-UPDRS | 0.3 Score on a scale | Standard Error 0.7 |
| Deferiprone 900 mg | Change in Score on the Part I Subscale of the MDS-UPDRS | 0.3 Score on a scale | Standard Error 0.7 |
| Deferiprone 1200 mg | Change in Score on the Part I Subscale of the MDS-UPDRS | 1.1 Score on a scale | Standard Error 0.7 |
p-value: >0.05ANCOVA
Secondary
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.
Time frame: Nine months
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the Combined Scores From Parts II and III of the MDS-UPDRS | 3.3 Score on a scale | Standard Error 1.6 |
| Deferiprone 300 mg | Change in the Combined Scores From Parts II and III of the MDS-UPDRS | 6.5 Score on a scale | Standard Error 1.6 |
| Deferiprone 600 mg | Change in the Combined Scores From Parts II and III of the MDS-UPDRS | -0.3 Score on a scale | Standard Error 1.7 |
| Deferiprone 900 mg | Change in the Combined Scores From Parts II and III of the MDS-UPDRS | 6.0 Score on a scale | Standard Error 1.7 |
| Deferiprone 1200 mg | Change in the Combined Scores From Parts II and III of the MDS-UPDRS | 4.3 Score on a scale | Standard Error 1.7 |
p-value: >0.05ANCOVA
Secondary
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.
Time frame: Nine months
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Total Score on the MDS-UPDRS | 4.1 Score on a scale | Standard Error 1.9 |
| Deferiprone 300 mg | Change in Total Score on the MDS-UPDRS | 7.8 Score on a scale | Standard Error 1.9 |
| Deferiprone 600 mg | Change in Total Score on the MDS-UPDRS | 0.5 Score on a scale | Standard Error 2.1 |
| Deferiprone 900 mg | Change in Total Score on the MDS-UPDRS | 6.6 Score on a scale | Standard Error 2.1 |
| Deferiprone 1200 mg | Change in Total Score on the MDS-UPDRS | 5.9 Score on a scale | Standard Error 2 |
p-value: >0.05ANCOVA
Secondary
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.
Time frame: 4 hours
Population: Pharmacokinetics (PK) population: Included all patients who had sufficient PK data to derive at least one PK parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 2.748 μg/mL | Standard Deviation 0.781 |
| Placebo | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 7.844 μg/mL | Standard Deviation 0.936 |
| Deferiprone 300 mg | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 12.419 μg/mL | Standard Deviation 2.218 |
| Deferiprone 300 mg | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 3.459 μg/mL | Standard Deviation 0.078 |
| Deferiprone 600 mg | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 5.080 μg/mL | Standard Deviation 2.614 |
| Deferiprone 600 mg | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 21.914 μg/mL | Standard Deviation 8.309 |
| Deferiprone 900 mg | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 7.942 μg/mL | Standard Deviation 2.192 |
| Deferiprone 900 mg | Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 32.632 μg/mL | Standard Deviation 2.167 |
Secondary
Safety of Deferiprone
Number of subjects with adverse events
Time frame: Nine months
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Safety of Deferiprone | 26 Participants |
| Deferiprone 300 mg | Safety of Deferiprone | 25 Participants |
| Deferiprone 600 mg | Safety of Deferiprone | 23 Participants |
| Deferiprone 900 mg | Safety of Deferiprone | 25 Participants |
| Deferiprone 1200 mg | Safety of Deferiprone | 25 Participants |
Secondary
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.
Time frame: 4 hours
Population: Pharmacokinetics population: Included all patients who had sufficient PK data to derive at least one PK parameter.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 2.00 Hours |
| Placebo | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 2.84 Hours |
| Deferiprone 300 mg | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 3.25 Hours |
| Deferiprone 300 mg | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 2.17 Hours |
| Deferiprone 600 mg | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 2.00 Hours |
| Deferiprone 600 mg | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 3.50 Hours |
| Deferiprone 900 mg | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone | 1.67 Hours |
| Deferiprone 900 mg | Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Serum deferiprone 3-O-glucuronide | 2.50 Hours |