Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)

• Sponsor: ApoPharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01741532
• Collaborator: Food and Drug Administration (FDA) (U.S. Fed)
• Enrollment: 89
• Locations: 4
• Arms: 2
• Actual Duration (Months): 49
• Patients Per Site: 22.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

A multi-center, placebo controlled, double-blind trial comparing the efficacy and safety of 18 months of treatment with deferiprone versus placebo in patients with PKAN.

This investigator-initiated trial was funded by the European Commission's Seventh Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No. 277984) to the TIRCON consortium (Treat Iron-Related Childhood-Onset Neurodegeneration) and by the FDA Office of Orphan Products Development (OOPD) (Dr. Elliott Vichinsky).

Condition or Disease	Intervention/Treatment	Phase
Pantothenate Kinase-Associated Neurodegeneration	Drug: Deferiprone oral solution; Drug: Placebo	Phase 3

Detailed Description

This is a multi-center, double-blind, randomized, placebo-controlled, 18-month study in patients with PKAN aged 4 years and older. Participants are randomized in a 2:1 ratio to receive either deferiprone oral solution or placebo, twice a day for 18 months. Efficacy assessments, an MRI scan to measure iron levels in the globus pallidus, pharmacokinetic evaluations, and safety assessments are conducted at specified time points. Following completion of the trial, eligible patients are invited to enroll in an 18-month extension study, TIRCON2012V1-EXT, in which all participants receive deferiprone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Placebo solution matched deferiprone oral solution in appearance, taste, and packaging
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Trial of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN)
• Actual Study Start Date: Dec 13, 2012
• Actual Primary Completion Date: Oct 21, 2016
• Actual Study Completion Date: Jan 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferiprone Deferiprone 80 mg/mL oral solution	Drug: Deferiprone oral solution; Deferiprone 80 mg/mL oral solution will be administered twice daily (b.i.d.) for 18 months. An initial dose of 5 mg/kg b.i.d. will be administered for 6 weeks. The dose will then be escalated to 10 mg/kg b.i.d. and finally to 15 mg/kg b.i.d.; Other Names: DFP L1
Placebo Comparator: Placebo Matching placebo solution	Drug: Placebo; A deferiprone matching placebo oral solution will be given twice daily for 18 months.

Outcome Measures

Primary Outcome Measures

1. Change in Score on Barry-Albright Dystonia Scale [Baseline to 18 Months]

   The Barry-Albright Dystonia (BAD) scale rates severity of dystonia (sustained muscle contractions causing twisting and repetitive movements or abnormal postures) in 8 body regions. The individual scores are summed to provide a total score ranging from 0 to 32, with higher scores indicating greater severity. The co-primary endpoint in this study was the change from baseline to Month 18 in BAD total score.

2. Score on Patient Global Impression of Improvement at End of Study [Month 18]

   The Patient Global Impression of Improvement (PGI-I) is a global index that assesses the response of a condition to a therapy by asking patients to rate their current state relative to their state at baseline. It consists of a 7-point rating scale, where 1=very much improved, 2= much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.

Secondary Outcome Measures

1. Change in Score on Unified Parkinson's Disease Rating Scale [Baseline to 18 Months]

   The Unified Parkinson's Disease Rating Scale (UPDRS) is the major rating scale used to assess severity of symptoms of Parkinson's disease, some of which are similar to those of PKAN. The UPDRS subscales used in this study were Part I: Mentation, Behavior and Mood, scored from 0 (best) to 16 (worst); Part II: Activities of Daily Living, scored from 0 (best) to 52 (worst); Part III: Motor Examination, scored from 0 (best) to 108 (worst); and Part VI: Schwab and England Activities of Daily Living Scale, scored from 0% (worst) to 100% (best).

2. Change in Score on Functional Independence Measure [Baseline to 18 Months]

   The Functional Independence Measure (FIM) scale is used to assess physical and cognitive disability in three areas of daily living: self-care, mobility, and cognition. Within each area, items are scored according to the level of assistance required to perform that activity of daily living. A score of 1-2 indicates that the patient is completely dependent on a helper to perform the task, a score of 3-5 indicates that the patient is moderately dependent, and a score of 6-7 indicates that no help is required. The individual scores are summed to provide a global score from 18 (worst) to 126 (best).

3. Change in Score on WeeFIM [Baseline to 18 Months]

   The WeeFIM is the pediatric version of the Functional Independence Measure scale, and is used to assess physical and cognitive disability in three areas of daily living: self-care, mobility, and cognition. Within each area, items are scored according to the level of assistance required to perform that activity of daily living. A score of 1-2 indicates that the patient is completely dependent on a helper to perform the task, a score of 3-5 indicates that the patient is moderately dependent, and a score of 6-7 indicates that no help is required. The individual scores are summed to provide a global score from 18 (worst) to 126 (best).

4. Change in Score on Pediatric Quality of Life [Baseline to 18 Months]

   The Pediatric Quality of Life (PedsQL) questionnaire is used to measure functional health and well-being from the patient's point of view. Separate versions of the questionnaire are available for children, young adults aged 18-25 years, and adults older than 25 years. Patients are asked to indicate how they have felt over the past month, and the scores of the 23 questions are used to generate an overall score that ranges from 0 (worst) to 100 (best).

5. Change in Score on Pittsburgh Sleep Quality Index [Baseline to 18 Months]

   The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that assesses sleep quality and disturbances over a 1-month time interval. A total of 19 individual items are used to generate 7 "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, and a score is generated that ranges from 0 (best) to 21 (worst).

6. Change in Level of Brain Iron [Baseline to 18 Months]

   Neurodegeneration in patients with PKAN is associated with localized brain iron accumulation, with the highest amount of accumulation seen in the globus pallidus, one of the main areas for motor control. MRI R2* scans of this region were performed at baseline and Month 18 in a subset of patients who did not have a deep brain stimulation (DBS) device implanted, and for whom the use of anesthesia, if required, was deemed acceptable by the investigator.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Inclusion Criteria:

• Males or females 4 years of age and older at screening visit;

• Have PKAN, confirmed by genetic testing (supporting evidence required);

• Barry-Albright Dystonia (BAD) total score ≥ 3 at the screening visit;

• Patients who have Deep Brain Stimulation (DBS) systems or baclofen pumps in place will be eligible for the study, but they must have had a stable setting for at least two months prior to the screening visit and stimulation parameters / pump settings must remain stable for the duration of the trial:

Main Exclusion Criteria:

• Evidence of iron deficiency defined by Fe:TIBC ratio <15%, or serum ferritin <12 ng/mL;

• Treatment with deferiprone in the past 12 months;

• Previous failure of treatment with deferiprone, or previous discontinuation of treatment with deferiprone due to adverse events;

• Conditions known to contraindicate the use of deferiprone (history of agranulocytosis or recurrent episodes of neutropenia);

• A serious, unstable chronic illness not related to PKAN condition during the past 3 months before screening visit including but not limited to: hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease;

• Evidence of abnormal liver or renal function (serum liver enzyme level(s) > 3 times upper limit of normal at screening) or abnormal creatinine levels at screening visit;

• Disorders associated with neutropenia (ANC < 1.5 x 10^{9/L) or thrombocytopenia (platelet count < 50 x 10}9/L) in the 12 months preceding the initiation of the study medication. Exception: for patients whose neutropenia was attributed by the treating physician to episodes of infection or to drugs associated with a decline in the neutrophil count and in whom the ANC has fully recovered at the screening visit;

• History of malignancy;

Other protocol inclusion or exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital & Research Center at Oakland	Oakland	California	United States	94609
2	Klinikum der Universität München	Munich		Germany	80336
3	Foundation Neurological Institute C. Besta	Milan		Italy	20133
4	Newcastle University Institute of Human Genetics	Newcastle Upon Tyne		United Kingdom	NE1 3BZ

Sponsors and Collaborators

• ApoPharma
• Food and Drug Administration (FDA)

Investigators

• Study Chair: Fernando Tricta, MD, ApoPharma Inc.
• Principal Investigator: Thomas Klopstock, MD, Friedrich-Baur-Institute, Department of Neurology, University of Munich Ziemssenstr
• Principal Investigator: Elliott Vichinsky, MD, Children's Hospital & Research Center at Oakland Hematology/ Oncology, Pediatric Rehabilitation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ApoPharma
• ClinicalTrials.gov Identifier: NCT01741532
• Other Study ID Numbers: TIRCON2012V1; 1R01FD004103-01
• First Posted: Dec 5, 2012
• Last Update Posted: Jul 5, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by ApoPharma: Pantothenate Kinase-associated Neurodegeneration; PKAN; NBIA; Deferiprone; Ferriprox; Neurodegeneration with brain iron accumulation
• Additional relevant MeSH terms: Pantothenate Kinase-Associated Neurodegeneration; Nerve Degeneration; Deferiprone

Study Results

Participant Flow

Recruitment Details	Patients were recruited at 4 study sites in Germany, Italy, the U.K., and the U.S.

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	Patients randomized to this arm received deferiprone oral solution 80 mg/mL at a dosage of up to 15 mg/kg twice a day for up 18 months.	Patients randomized to this arm received matching placebo solution twice a day, for up to 18 months, at a volume corresponding to that taken by patients who were receiving active product.
Period Title: Overall Study
STARTED	59	30
Exposed	58	30
Provided Post-baseline Efficacy Data	58	28
COMPLETED	49	27
NOT COMPLETED	10	3

Baseline Characteristics

Arm/Group Title	Deferiprone	Placebo	Total
Arm/Group Description	Deferiprone 80 mg/mL oral solution, 15 mg/kg b.i.d. for 18 months	Matching volume of placebo solution, twice daily for 18 months	Total of all reporting groups
Overall Participants	59	30	89
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.8 (10.7)	19.2 (12.5)	20.2 (11.3)
Sex: Female, Male (Count of Participants)
Female	25 42.4%	17 56.7%	42 47.2%
Male	34 57.6%	13 43.3%	47 52.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	6 10.2%	1 3.3%	7 7.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 3.4%	0 0%	2 2.2%
White	51 86.4%	28 93.3%	79 88.8%
More than one race	0 0%	1 3.3%	1 1.1%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Score on Barry-Albright Dystonia Scale
Description	The Barry-Albright Dystonia (BAD) scale rates severity of dystonia (sustained muscle contractions causing twisting and repetitive movements or abnormal postures) in 8 body regions. The individual scores are summed to provide a total score ranging from 0 to 32, with higher scores indicating greater severity. The co-primary endpoint in this study was the change from baseline to Month 18 in BAD total score.
Time Frame	Baseline to 18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	Patients randomized to this arm received deferiprone oral solution 80 mg/mL at a dosage of up to 15 mg/kg twice a day for up to 18 months.	Patients randomized to this arm received matching placebo solution twice a day, for up to 18 months, at a volume corresponding to what was given for the active product.
Measure Participants	58	28
Least Squares Mean (Standard Error) [score on a scale]	2.48 (0.63)	3.99 (0.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0761
	Comments
	Method	Mixed Models Analysis
	Comments

2. Primary Outcome

Title	Score on Patient Global Impression of Improvement at End of Study
Description	The Patient Global Impression of Improvement (PGI-I) is a global index that assesses the response of a condition to a therapy by asking patients to rate their current state relative to their state at baseline. It consists of a 7-point rating scale, where 1=very much improved, 2= much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	Patients randomized to this arm received deferiprone oral solution 80 mg/mL at a dosage of up to 15 mg/kg twice a day for up 18 months.	Patients randomized to this arm received matching placebo solution twice a day, for up to 18 months, at a volume corresponding to that taken by patients who were receiving active product.
Measure Participants	58	28
Least Squares Mean (Standard Error) [score on a scale]	4.55 (0.30)	4.66 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7279
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Change in Score on Unified Parkinson's Disease Rating Scale
Description	The Unified Parkinson's Disease Rating Scale (UPDRS) is the major rating scale used to assess severity of symptoms of Parkinson's disease, some of which are similar to those of PKAN. The UPDRS subscales used in this study were Part I: Mentation, Behavior and Mood, scored from 0 (best) to 16 (worst); Part II: Activities of Daily Living, scored from 0 (best) to 52 (worst); Part III: Motor Examination, scored from 0 (best) to 108 (worst); and Part VI: Schwab and England Activities of Daily Living Scale, scored from 0% (worst) to 100% (best).
Time Frame	Baseline to 18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	Patients randomized to this arm received deferiprone oral solution 80 mg/mL at a dosage of up to 15 mg/kg twice a day for up 18 months.	Patients randomized to this arm received matching placebo solution twice a day, for up to 18 months, at a volume corresponding to that taken by patients who were receiving active product.
Measure Participants	58	28
UPDRS Part I	-0.25 (0.43)	-0.07 (0.55)
UPDRS Part II	1.09 (1.19)	2.36 (1.52)
UPDRS Part III	5.38 (2.20)	2.06 (2.79)
UPDRS Part VI	-2.17 (2.94)	-7.66 (3.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments	Comparison of treatment groups on change in score on UPDRS Part I
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7228
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments	Comparison of treatment groups on change in score on UPDRS Part II
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3677
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments	Comparison of treatment groups on change in score on UPDRS Part III
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2182
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments	Comparison of treatment groups on change in score on UPDRS Part VI
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1749
	Comments
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Change in Score on Functional Independence Measure
Description	The Functional Independence Measure (FIM) scale is used to assess physical and cognitive disability in three areas of daily living: self-care, mobility, and cognition. Within each area, items are scored according to the level of assistance required to perform that activity of daily living. A score of 1-2 indicates that the patient is completely dependent on a helper to perform the task, a score of 3-5 indicates that the patient is moderately dependent, and a score of 6-7 indicates that no help is required. The individual scores are summed to provide a global score from 18 (worst) to 126 (best).
Time Frame	Baseline to 18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	Patients randomized to this arm received deferiprone oral solution 80 mg/mL at a dosage of up to 15 mg/kg twice a day for up 18 months.	Patients randomized to this arm received matching placebo solution twice a day, for up to 18 months, at a volume corresponding to that taken by patients who were receiving active product.
Measure Participants	58	28
Least Squares Mean (Standard Error) [score on a scale]	5.40 (2.36)	0.69 (3.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1524
	Comments
	Method	Mixed Models Analysis
	Comments

5. Secondary Outcome

Title	Change in Score on WeeFIM
Description	The WeeFIM is the pediatric version of the Functional Independence Measure scale, and is used to assess physical and cognitive disability in three areas of daily living: self-care, mobility, and cognition. Within each area, items are scored according to the level of assistance required to perform that activity of daily living. A score of 1-2 indicates that the patient is completely dependent on a helper to perform the task, a score of 3-5 indicates that the patient is moderately dependent, and a score of 6-7 indicates that no help is required. The individual scores are summed to provide a global score from 18 (worst) to 126 (best).
Time Frame	Baseline to 18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	Patients randomized to this arm received deferiprone oral solution 80 mg/mL at a dosage of up to 15 mg/kg twice a day for up 18 months.	Patients randomized to this arm received matching placebo solution twice a day, for up to 18 months, at a volume corresponding to that taken by patients who were receiving active product.
Measure Participants	58	28
Least Squares Mean (Standard Error) [score on a scale]	4.91 (5.30)	-2.40 (5.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2026
	Comments
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Change in Score on Pediatric Quality of Life
Description	The Pediatric Quality of Life (PedsQL) questionnaire is used to measure functional health and well-being from the patient's point of view. Separate versions of the questionnaire are available for children, young adults aged 18-25 years, and adults older than 25 years. Patients are asked to indicate how they have felt over the past month, and the scores of the 23 questions are used to generate an overall score that ranges from 0 (worst) to 100 (best).
Time Frame	Baseline to 18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	Patients randomized to this arm received deferiprone oral solution 80 mg/mL at a dosage of up to 15 mg/kg twice a day for up 18 months.	Patients randomized to this arm received matching placebo solution twice a day, for up to 18 months, at a volume corresponding to that taken by patients who were receiving active product.
Measure Participants	58	28
Patient self-report, total score	1.21 (3.68)	1.34 (4.49)
Parent proxy-report, total score	-4.90 (3.99)	-2.37 (4.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments	Patient self-report, total score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9759
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments	Parent proxy-report, total score
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5781
	Comments
	Method	Mixed Models Analysis
	Comments

7. Secondary Outcome

Title	Change in Score on Pittsburgh Sleep Quality Index
Description	The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that assesses sleep quality and disturbances over a 1-month time interval. A total of 19 individual items are used to generate 7 "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction, and a score is generated that ranges from 0 (best) to 21 (worst).
Time Frame	Baseline to 18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	Patients randomized to this arm received deferiprone oral solution 80 mg/mL at a dosage of up to 15 mg/kg twice a day for up 18 months.	Patients randomized to this arm received matching placebo solution twice a day, for up to 18 months, at a volume corresponding to that taken by patients who were receiving active product.
Measure Participants	58	28
Least Squares Mean (Standard Error) [score on a scale]	0.48 (0.61)	0.14 (0.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6323
	Comments
	Method	Mixed Models Analysis
	Comments

8. Secondary Outcome

Title	Change in Level of Brain Iron
Description	Neurodegeneration in patients with PKAN is associated with localized brain iron accumulation, with the highest amount of accumulation seen in the globus pallidus, one of the main areas for motor control. MRI R2* scans of this region were performed at baseline and Month 18 in a subset of patients who did not have a deep brain stimulation (DBS) device implanted, and for whom the use of anesthesia, if required, was deemed acceptable by the investigator.
Time Frame	Baseline to 18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferiprone	Placebo
Arm/Group Description	The subset of deferiprone recipients who underwent MRI R2* imaging	The subset of placebo recipients who underwent MRI R2* imaging
Measure Participants	24	16
Least Squares Mean (Standard Error) [Hz]	-36.1 (3.11)	-0.50 (3.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferiprone, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0000
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Adverse events were collected from baseline until 30 days after the last dose of study medication.
Arm/Group Title	Deferiprone		Placebo
Arm/Group Description	Study participants who received at least one dose of deferiprone in the trial		Study participants who received at least one dose of placebo in the trial
All Cause Mortality
	Deferiprone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/30 (0%)
Serious Adverse Events
	Deferiprone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/58 (31%)		10/30 (33.3%)
Blood and lymphatic system disorders
Neutropenia	5/58 (8.6%)	7	2/30 (6.7%)	2
Gastrointestinal disorders
Intestinal dilatation	1/58 (1.7%)	1	0/30 (0%)	0
Intestinal obstruction	1/58 (1.7%)	1	0/30 (0%)	0
Nausea	0/58 (0%)	0	1/30 (3.3%)	1
Volvulus	1/58 (1.7%)	1	0/30 (0%)	0
Vomiting	1/58 (1.7%)	1	1/30 (3.3%)	1
General disorders
Condition aggravated	0/58 (0%)	0	1/30 (3.3%)	1
Obstruction	1/58 (1.7%)	1	0/30 (0%)	0
Pyrexia	1/58 (1.7%)	1	0/30 (0%)	0
Infections and infestations
Bacterial disease carrier	1/58 (1.7%)	1	0/30 (0%)	0
Bronchitis	2/58 (3.4%)	2	0/30 (0%)	0
Cytomegalovirus infection	0/58 (0%)	0	1/30 (3.3%)	1
Device related infection	1/58 (1.7%)	1	0/30 (0%)	0
Pneumonia	2/58 (3.4%)	2	0/30 (0%)	0
Pneumonia bacterial	0/58 (0%)	0	1/30 (3.3%)	1
Urinary tract infection	0/58 (0%)	0	1/30 (3.3%)	1
Wound infection	1/58 (1.7%)	1	0/30 (0%)	0
Injury, poisoning and procedural complications
Chemical eye injury	1/58 (1.7%)	1	0/30 (0%)	0
Postoperative ileus	1/58 (1.7%)	1	0/30 (0%)	0
Toxicity to various agents	1/58 (1.7%)	1	0/30 (0%)	0
Unintentional medical device removal	1/58 (1.7%)	1	0/30 (0%)	0
Investigations
Medical observation	0/58 (0%)	0	1/30 (3.3%)	1
Transaminases increased	0/58 (0%)	0	1/30 (3.3%)	1
Metabolism and nutrition disorders
Dehydration	0/58 (0%)	0	1/30 (3.3%)	1
Nervous system disorders
Dystonia	3/58 (5.2%)	3	2/30 (6.7%)	3
Hypotonia	0/58 (0%)	0	1/30 (3.3%)	1
Lethargy	0/58 (0%)	0	1/30 (3.3%)	1
Oromandibular dystonia	1/58 (1.7%)	1	0/30 (0%)	0
Syncope	1/58 (1.7%)	1	1/30 (3.3%)	1
Product Issues
Device malfunction	1/58 (1.7%)	1	0/30 (0%)	0
Psychiatric disorders
Staring	0/58 (0%)	0	1/30 (3.3%)	1
Renal and urinary disorders
Urinary bladder rupture	1/58 (1.7%)	1	0/30 (0%)	0
Respiratory, thoracic and mediastinal disorders
Choking	1/58 (1.7%)	1	0/30 (0%)	0
Cough	1/58 (1.7%)	1	0/30 (0%)	0
Pneumonia aspiration	1/58 (1.7%)	1	1/30 (3.3%)	1
Respiratory disorder	1/58 (1.7%)	1	0/30 (0%)	0
Respiratory failure	0/58 (0%)	0	1/30 (3.3%)	1
Surgical and medical procedures
Colectomy	1/58 (1.7%)	1	0/30 (0%)	0
Gastrointestinal tube insertion	1/58 (1.7%)	1	1/30 (3.3%)	1
Intestinal anastomosis	1/58 (1.7%)	1	0/30 (0%)	0
Intrathecal pump insertion	1/58 (1.7%)	2	0/30 (0%)	0
Laparotomy	1/58 (1.7%)	1	0/30 (0%)	0
Medical device battery replacement	2/58 (3.4%)	2	1/30 (3.3%)	1
Nasal septal operation	0/58 (0%)	0	1/30 (3.3%)	1
Tracheostomy	1/58 (1.7%)	3	0/30 (0%)	0
Tracheostomy tube removal	1/58 (1.7%)	1	0/30 (0%)	0
Wound treatment	1/58 (1.7%)	1	0/30 (0%)	0
Vascular disorders
Thrombosis	1/58 (1.7%)	1	0/30 (0%)	0
Other (Not Including Serious) Adverse Events
	Deferiprone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/58 (98.3%)		30/30 (100%)
Blood and lymphatic system disorders
Anaemia	12/58 (20.7%)	23	0/30 (0%)	0
Leukocytosis	2/58 (3.4%)	3	2/30 (6.7%)	2
Ear and labyrinth disorders
Ear pain	1/58 (1.7%)	1	3/30 (10%)	3
Gastrointestinal disorders
Abdominal pain upper	4/58 (6.9%)	6	5/30 (16.7%)	7
Constipation	2/58 (3.4%)	3	4/30 (13.3%)	4
Diarrhoea	4/58 (6.9%)	7	3/30 (10%)	8
Influenza	3/58 (5.2%)	4	0/30 (0%)	0
Toothache	2/58 (3.4%)	2	2/30 (6.7%)	3
Vomiting	9/58 (15.5%)	17	8/30 (26.7%)	19
General disorders
Abasia	2/58 (3.4%)	2	2/30 (6.7%)	2
Condition aggravated	10/58 (17.2%)	12	9/30 (30%)	10
Pain	4/58 (6.9%)	4	0/30 (0%)	0
Pyrexia	16/58 (27.6%)	34	13/30 (43.3%)	28
Infections and infestations
Bronchitis	7/58 (12.1%)	15	2/30 (6.7%)	2
Ear infection	0/58 (0%)	0	2/30 (6.7%)	2
Gastrointestinal infection	3/58 (5.2%)	3	3/30 (10%)	4
Localised infection	0/58 (0%)	0	2/30 (6.7%)	2
Nasopharyngitis	11/58 (19%)	20	6/30 (20%)	10
Rhinitis	4/58 (6.9%)	6	1/30 (3.3%)	1
Upper respiratory tract infection	8/58 (13.8%)	9	4/30 (13.3%)	5
Viral infection	4/58 (6.9%)	5	1/30 (3.3%)	1
Injury, poisoning and procedural complications
Arthropod bite	1/58 (1.7%)	1	2/30 (6.7%)	4
Contusion	2/58 (3.4%)	2	2/30 (6.7%)	2
Fall	2/58 (3.4%)	3	2/30 (6.7%)	2
Laceration	6/58 (10.3%)	15	3/30 (10%)	3
Skin abrasion	0/58 (0%)	0	2/30 (6.7%)	4
Investigations
Blood iron decreased	3/58 (5.2%)	3	2/30 (6.7%)	2
Body temperature increased	3/58 (5.2%)	3	0/30 (0%)	0
Neutrophil count decreased	10/58 (17.2%)	18	3/30 (10%)	20
Serum ferritin decreased	19/58 (32.8%)	23	5/30 (16.7%)	5
White blood cell count increased	0/58 (0%)	0	2/30 (6.7%)	2
Metabolism and nutrition disorders
Iron deficiency	9/58 (15.5%)	9	3/30 (10%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	8/58 (13.8%)	8	1/30 (3.3%)	1
Back pain	3/58 (5.2%)	3	2/30 (6.7%)	8
Muscle spasms	3/58 (5.2%)	4	2/30 (6.7%)	2
Pain in extremity	10/58 (17.2%)	13	4/30 (13.3%)	7
Nervous system disorders
Aphasia	3/58 (5.2%)	3	2/30 (6.7%)	2
Drooling	2/58 (3.4%)	2	2/30 (6.7%)	2
Dystonia	25/58 (43.1%)	49	14/30 (46.7%)	20
Freezing phenomenon	0/58 (0%)	0	3/30 (10%)	3
Headache	13/58 (22.4%)	43	9/30 (30%)	30
Migraine	3/58 (5.2%)	21	0/30 (0%)	0
Renal and urinary disorders
Urinary incontinence	3/58 (5.2%)	4	2/30 (6.7%)	2
Reproductive system and breast disorders
Dysmenorrhoea	0/58 (0%)	0	2/30 (6.7%)	8
Respiratory, thoracic and mediastinal disorders
Cough	10/58 (17.2%)	12	5/30 (16.7%)	9
Nasal congestion	1/58 (1.7%)	1	2/30 (6.7%)	3
Oropharyngeal pain	9/58 (15.5%)	10	3/30 (10%)	3
Rhinorrhoea	4/58 (6.9%)	6	2/30 (6.7%)	2
Skin and subcutaneous tissue disorders
Hyperhidrosis	3/58 (5.2%)	3	1/30 (3.3%)	1
Rash	4/58 (6.9%)	4	1/30 (3.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor retained title to and the right to publish all documentation, records, raw data, specimens or other work product generated in connection with the trial. Such publications shall not be made without the prior written consent of Sponsor. Neither Party will use the other Party's name in connection with any publication or promotion without the other Party's prior written consent. However, Sponsor has the right to publish appropriate information in order to satisfy regulatory requirements.