Trial Outcomes & Findings for Efficacy and Safety Study of Deferiprone in Patients With Pantothenate Kinase-associated Neurodegeneration (PKAN) (NCT NCT01741532)

Last Updated: 2019-07-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

89 participants

Primary outcome timeframe

Baseline to 18 Months

Results posted on

2019-07-05

Participant Flow

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

Participant milestones

Participant milestones
Measure	Deferiprone 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.	Placebo 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.
Overall Study STARTED	59	30
Overall Study Exposed	58	30
Overall Study Provided Post-baseline Efficacy Data	58	28
Overall Study COMPLETED	49	27
Overall Study NOT COMPLETED	10	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Deferiprone 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.	Placebo 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.
Overall Study Adverse Event	4	0
Overall Study Withdrawal by Subject	1	1
Overall Study Protocol Violation	0	1
Overall Study Worsening of the disease	3	1
Overall Study Sponsor decision	1	0
Overall Study Medical event	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Deferiprone n=59 Participants Deferiprone 80 mg/mL oral solution, 15 mg/kg b.i.d. for 18 months	Placebo n=30 Participants Matching volume of placebo solution, twice daily for 18 months	Total n=89 Participants Total of all reporting groups
Age, Continuous	20.8 years STANDARD_DEVIATION 10.7 • n=5 Participants	19.2 years STANDARD_DEVIATION 12.5 • n=7 Participants	20.2 years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	17 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	13 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	51 Participants n=5 Participants	28 Participants n=7 Participants	79 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 18 Months

Outcome measures

Outcome measures
Measure	Deferiprone n=58 Participants 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.	Placebo n=28 Participants 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.
Change in Score on Barry-Albright Dystonia Scale	2.48 score on a scale Standard Error 0.63	3.99 score on a scale Standard Error 0.82

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Deferiprone n=58 Participants 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.	Placebo n=28 Participants 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.
Score on Patient Global Impression of Improvement at End of Study	4.55 score on a scale Standard Error 0.30	4.66 score on a scale Standard Error 0.38

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Deferiprone n=58 Participants 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.	Placebo n=28 Participants 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.
Change in Score on Unified Parkinson's Disease Rating Scale UPDRS Part I	-0.25 score on a scale Standard Error 0.43	-0.07 score on a scale Standard Error 0.55
Change in Score on Unified Parkinson's Disease Rating Scale UPDRS Part II	1.09 score on a scale Standard Error 1.19	2.36 score on a scale Standard Error 1.52
Change in Score on Unified Parkinson's Disease Rating Scale UPDRS Part III	5.38 score on a scale Standard Error 2.20	2.06 score on a scale Standard Error 2.79
Change in Score on Unified Parkinson's Disease Rating Scale UPDRS Part VI	-2.17 score on a scale Standard Error 2.94	-7.66 score on a scale Standard Error 3.85

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Deferiprone n=58 Participants 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.	Placebo n=28 Participants 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.
Change in Score on Functional Independence Measure	5.40 score on a scale Standard Error 2.36	0.69 score on a scale Standard Error 3.34

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Deferiprone n=58 Participants 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.	Placebo n=28 Participants 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.
Change in Score on WeeFIM	4.91 score on a scale Standard Error 5.30	-2.40 score on a scale Standard Error 5.42

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Deferiprone n=58 Participants 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.	Placebo n=28 Participants 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.
Change in Score on Pediatric Quality of Life Patient self-report, total score	1.21 score on a scale Standard Error 3.68	1.34 score on a scale Standard Error 4.49
Change in Score on Pediatric Quality of Life Parent proxy-report, total score	-4.90 score on a scale Standard Error 3.99	-2.37 score on a scale Standard Error 4.90

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Deferiprone n=58 Participants 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.	Placebo n=28 Participants 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.
Change in Score on Pittsburgh Sleep Quality Index	0.48 score on a scale Standard Error 0.61	0.14 score on a scale Standard Error 0.80

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Deferiprone n=24 Participants 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.	Placebo n=16 Participants 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.
Change in Level of Brain Iron	-36.1 Hz Standard Error 3.11	-0.50 Hz Standard Error 3.97

Adverse Events

Deferiprone

Serious events: 18 serious events

Other events: 57 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Caroline Fradette

ApoPharma Inc.

Phone: 416-401-7543

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Deferiprone n=58 participants at risk Study participants who received at least one dose of deferiprone in the trial	Placebo n=30 participants at risk Study participants who received at least one dose of placebo in the trial
Blood and lymphatic system disorders Neutropenia	8.6% 5/58 • Number of events 7 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Intestinal dilatation	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Intestinal obstruction	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Nausea	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Volvulus	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Vomiting	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
General disorders Condition aggravated	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
General disorders Obstruction	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
General disorders Pyrexia	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Bacterial disease carrier	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Bronchitis	3.4% 2/58 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Cytomegalovirus infection	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Device related infection	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Pneumonia	3.4% 2/58 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Pneumonia bacterial	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Urinary tract infection	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Wound infection	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Chemical eye injury	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Postoperative ileus	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Toxicity to various agents	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Unintentional medical device removal	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Investigations Medical observation	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Investigations Transaminases increased	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Metabolism and nutrition disorders Dehydration	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Dystonia	5.2% 3/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Hypotonia	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Lethargy	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Oromandibular dystonia	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Syncope	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Product Issues Device malfunction	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Psychiatric disorders Staring	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Renal and urinary disorders Urinary bladder rupture	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Choking	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Colectomy	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Gastrointestinal tube insertion	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Intestinal anastomosis	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Intrathecal pump insertion	1.7% 1/58 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Laparotomy	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Medical device battery replacement	3.4% 2/58 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Nasal septal operation	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Tracheostomy	1.7% 1/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Tracheostomy tube removal	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Surgical and medical procedures Wound treatment	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Vascular disorders Thrombosis	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.

Measure	Deferiprone n=58 participants at risk Study participants who received at least one dose of deferiprone in the trial	Placebo n=30 participants at risk Study participants who received at least one dose of placebo in the trial
Blood and lymphatic system disorders Anaemia	20.7% 12/58 • Number of events 23 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Blood and lymphatic system disorders Leukocytosis	3.4% 2/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Ear and labyrinth disorders Ear pain	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	10.0% 3/30 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Abdominal pain upper	6.9% 4/58 • Number of events 6 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	16.7% 5/30 • Number of events 7 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Constipation	3.4% 2/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	13.3% 4/30 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Diarrhoea	6.9% 4/58 • Number of events 7 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	10.0% 3/30 • Number of events 8 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Influenza	5.2% 3/58 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Toothache	3.4% 2/58 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Gastrointestinal disorders Vomiting	15.5% 9/58 • Number of events 17 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	26.7% 8/30 • Number of events 19 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
General disorders Abasia	3.4% 2/58 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
General disorders Condition aggravated	17.2% 10/58 • Number of events 12 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	30.0% 9/30 • Number of events 10 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
General disorders Pain	6.9% 4/58 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
General disorders Pyrexia	27.6% 16/58 • Number of events 34 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	43.3% 13/30 • Number of events 28 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Bronchitis	12.1% 7/58 • Number of events 15 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Ear infection	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Gastrointestinal infection	5.2% 3/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	10.0% 3/30 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Localised infection	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Nasopharyngitis	19.0% 11/58 • Number of events 20 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	20.0% 6/30 • Number of events 10 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Rhinitis	6.9% 4/58 • Number of events 6 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Upper respiratory tract infection	13.8% 8/58 • Number of events 9 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	13.3% 4/30 • Number of events 5 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Infections and infestations Viral infection	6.9% 4/58 • Number of events 5 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Arthropod bite	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Contusion	3.4% 2/58 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Fall	3.4% 2/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Laceration	10.3% 6/58 • Number of events 15 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	10.0% 3/30 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Investigations Blood iron decreased	5.2% 3/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Investigations Body temperature increased	5.2% 3/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Investigations Neutrophil count decreased	17.2% 10/58 • Number of events 18 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	10.0% 3/30 • Number of events 20 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Investigations Serum ferritin decreased	32.8% 19/58 • Number of events 23 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	16.7% 5/30 • Number of events 5 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Investigations White blood cell count increased	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Metabolism and nutrition disorders Iron deficiency	15.5% 9/58 • Number of events 9 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	10.0% 3/30 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	13.8% 8/58 • Number of events 8 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	5.2% 3/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 8 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	5.2% 3/58 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	17.2% 10/58 • Number of events 13 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	13.3% 4/30 • Number of events 7 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Aphasia	5.2% 3/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Drooling	3.4% 2/58 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Dystonia	43.1% 25/58 • Number of events 49 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	46.7% 14/30 • Number of events 20 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Freezing phenomenon	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	10.0% 3/30 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Headache	22.4% 13/58 • Number of events 43 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	30.0% 9/30 • Number of events 30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Nervous system disorders Migraine	5.2% 3/58 • Number of events 21 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	0.00% 0/30 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Renal and urinary disorders Urinary incontinence	5.2% 3/58 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/58 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 8 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	17.2% 10/58 • Number of events 12 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	16.7% 5/30 • Number of events 9 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.7% 1/58 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	15.5% 9/58 • Number of events 10 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	10.0% 3/30 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.9% 4/58 • Number of events 6 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	6.7% 2/30 • Number of events 2 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.2% 3/58 • Number of events 3 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.
Skin and subcutaneous tissue disorders Rash	6.9% 4/58 • Number of events 4 • Adverse events were collected from baseline until 30 days after the last dose of study medication.	3.3% 1/30 • Number of events 1 • Adverse events were collected from baseline until 30 days after the last dose of study medication.