Efficacy and Safety Study of Fosmetpantotenate (RE-024) i... | NCT03041116

Label	Type	Description	Intervention Names
Fosmetpantotenate	Experimental	Administered as powder for reconstitution.	Drug: Fosmetpantotenate
Placebo	Placebo Comparator	Administered as powder for reconstitution.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Fosmetpantotenate	Drug	Daily dosing	Fosmetpantotenate	RE-024

Measure	Description	Time Frame
Change From Baseline In The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living (PKAN-ADL) Total Score To The End Of The 24-week Double-blind Period	Change from baseline to Week 24 activities of daily living was assessed on the PKAN-ADL scale based on the Unified Parkinson's Disease Rating Scale (UPDRS) Part II. The PKAN-ADL is a validated measure of the participant's ability to complete ADL that are impacted by the diffuse motor manifestations of PKAN. It consists of 12 items related to activities of daily living, including eating, dressing, and walking. Each item has responses ranging from 0-4, with a higher value indicating greater disability in the given activity. To compute the total score, responses are summed across the 12 items. The available range of total scores on the PKAN-ADL scale was from 0 (no ADL affected) to 48 (ADL highly affected). The reported least square mean (LSM) was adjusted for baseline score and age group from the Type III analysis. A decrease in score indicates improvement in symptoms.	Baseline (Day -1), Week 24
Number Of Participants With At Least 1 (≥1) Treatment-emergent Adverse Event (TEAE) And Treatment-emergent Serious Adverse Event (TESAE) During The 24-week Double-blind Period	An adverse event (AE) is any untoward medical occurrence associated with the use of the investigational product (IP; active or placebo) in a participant, without regard to possibility of causal relationship with IP. A serious adverse event (SAE) is an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of death from AE); persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious medical events. The TEAEs in the double-blind period are defined as AEs that are new or are a worsening of an existing condition that begins from day of first dose of IP until day after last dose for double-blind treatment period.	From Screening until end of Week 24

Measure	Description	Time Frame
Absolute Change From Baseline In The UPDRS Part 3 (UPDRS-III) Total Score To The End Of The 24-week Double-blind Period	The UPDRS is a comprehensive assessment of the burden and severity of signs and symptoms of Parkinsonism captured via systematic interview and neurological examination. The UPDRS-III is a standardized neurological examination that evaluates the performance of movements commonly affected in Parkinson's disease, PKAN, and other movement disorders. Part III of the UPDRS consists of 27 items, which correspond to 14 domains related to motor abilities such as tremor, stability, and bradykinesia. Each item has responses ranging from 0-4. To compute the UPDRS-III total score, responses are summed across the 27 items, and accordingly, range from 0-108. For domain totals, responses are summed across all of the items in a given domain (when domain corresponds to multiple items). An increase in score indicates greater disability. The reported LSM was adjusted for baseline score and age group from the Type III analysis.

Name	Affiliation	Role
Thomas Klopstock, MD	Klinikum der Universität München	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Travere Investigational Site		Irvine	California	92697	United States
Travere Investigational Site

PubMed Identifier	Type	Citation	Retractions
31055958	Result	Klopstock T, Escolar ML, Marshall RD, Perez-Duenas B, Tuller S, Videnovic A, Greblikas F. The FOsmetpantotenate Replacement Therapy (FORT) randomized, double-blind, Placebo-controlled pivotal trial: Study design and development methodology of a novel primary efficacy outcome in patients with pantothenate kinase-associated neurodegeneration. Clin Trials. 2019 Aug;16(4):410-418. doi: 10.1177/1740774519845673. Epub 2019 May 6.

ID	Title	Description
FG000	Fosmetpantotenate	Double-blind Period: each randomized participant received an oral dose of fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose 3 times daily (TID) from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants continued treatment with fosmetpantotenate according to the dose they were receiving at the end of the double-blind period. No dose escalation was required.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 23, 2019	Sep 28, 2020

ID	Title	Description
BG000	Fosmetpantotenate	Double-blind Period: each randomized participant received an oral dose of fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants continued treatment with fosmetpantotenate according to the dose they were receiving at the end of the double-blind period. No dose escalation was required.
BG001	Placebo	Double-blind Period: each randomized participant received an oral dose of placebo matched to fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants started treatment with fosmetpantotenate according to the placebo dose they were receiving at the end of the double-blind period. No dose escalation was required.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00041 BG00143 BG00284

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline In The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living (PKAN-ADL) Total Score To The End Of The 24-week Double-blind Period

Change from baseline to Week 24 activities of daily living was assessed on the PKAN-ADL scale based on the Unified Parkinson's Disease Rating Scale (UPDRS) Part II. The PKAN-ADL is a validated measure of the participant's ability to complete ADL that are impacted by the diffuse motor manifestations of PKAN. It consists of 12 items related to activities of daily living, including eating, dressing, and walking. Each item has responses ranging from 0-4, with a higher value indicating greater disability in the given activity. To compute the total score, responses are summed across the 12 items. The available range of total scores on the PKAN-ADL scale was from 0 (no ADL affected) to 48 (ADL highly affected). The reported least square mean (LSM) was adjusted for baseline score and age group from the Type III analysis. A decrease in score indicates improvement in symptoms.

Double-blind Full Analysis Set: any participant who received at least 1 dose of study drug.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline (Day -1), Week 24

ID	Title	Description
OG000	Fosmetpantotenate	Double-blind Period: each randomized participant received an oral dose of fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants continued treatment with fosmetpantotenate according to the dose they were receiving at the end of the double-blind period. No dose escalation was required.
OG001	Placebo	Double-blind Period: each randomized participant received an oral dose of placebo matched to fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants started treatment with fosmetpantotenate according to the placebo dose they were receiving at the end of the double-blind period. No dose escalation was required.

Units	Counts
Participants	OG00041 OG00143

Title

Denominators

Categories

Title	Measurements
	OG000-1.3± 0.56 OG001-1.3± 0.58

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		=0.9115	p-value was derived from test of contrast between treatment effects using LSM estimate, adjusted for baseline score and age group from Type III analysis. The test of contrast at Week 24 was considered the primary comparison.	Difference in LS Mean	-0.1	Standard Error of the Mean	0.8	2-Sided	95	-1.69	1.51					Superiority

Primary

Number Of Participants With At Least 1 (≥1) Treatment-emergent Adverse Event (TEAE) And Treatment-emergent Serious Adverse Event (TESAE) During The 24-week Double-blind Period

An adverse event (AE) is any untoward medical occurrence associated with the use of the investigational product (IP; active or placebo) in a participant, without regard to possibility of causal relationship with IP. A serious adverse event (SAE) is an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of death from AE); persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious medical events. The TEAEs in the double-blind period are defined as AEs that are new or are a worsening of an existing condition that begins from day of first dose of IP until day after last dose for double-blind treatment period.

Safety Population: any participant who received at least 1 dose of study drug during any period of the study.

Posted

Count of Participants

Participants

From Screening until end of Week 24

ID	Title	Description
OG000	Fosmetpantotenate	Double-blind Period: each randomized participant received an oral dose of fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants continued treatment with fosmetpantotenate according to the dose they were receiving at the end of the double-blind period. No dose escalation was required.

Secondary

Absolute Change From Baseline In The UPDRS Part 3 (UPDRS-III) Total Score To The End Of The 24-week Double-blind Period

The UPDRS is a comprehensive assessment of the burden and severity of signs and symptoms of Parkinsonism captured via systematic interview and neurological examination. The UPDRS-III is a standardized neurological examination that evaluates the performance of movements commonly affected in Parkinson's disease, PKAN, and other movement disorders. Part III of the UPDRS consists of 27 items, which correspond to 14 domains related to motor abilities such as tremor, stability, and bradykinesia. Each item has responses ranging from 0-4. To compute the UPDRS-III total score, responses are summed across the 27 items, and accordingly, range from 0-108. For domain totals, responses are summed across all of the items in a given domain (when domain corresponds to multiple items). An increase in score indicates greater disability. The reported LSM was adjusted for baseline score and age group from the Type III analysis.

Double-blind Full Analysis Set: any participant who received at least 1 dose of study drug.

Posted

Mean

Standard Deviation

units on a scale

Baseline (Day -1), Week 24

ID	Title	Description
OG000	Fosmetpantotenate	Double-blind Period: each randomized participant received an oral dose of fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants continued treatment with fosmetpantotenate according to the dose they were receiving at the end of the double-blind period. No dose escalation was required.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypersensitivity	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG0030 events0 affected43 at risk EG0041 events1 affected41 at risk EG0050 events0 affected37 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment	EG0008 events7 affected41 at risk EG0011 events1 affected37 at risk EG0026 events5 affected41 at risk EG003
Discomfort	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Feeling cold	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Gait disturbance	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
General physical health deterioration	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Generalised oedema	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Medical device site inflammation	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Medical device site rash	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0012 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Influenza like illness	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Oedema peripheral	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0022 events2 affected41 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0022 events2 affected41 at risk EG003
Adjustment disorder with depressed mood	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Restlessness	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Affect lability	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Gastrostomy tube site complication	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0010 events0 affected37 at risk EG0022 events2 affected41 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0012 events2 affected37 at risk EG0020 events0 affected41 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0011 events1 affected37 at risk EG0022 events2 affected41 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Face injury	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected41 at risk EG0011 events1 affected37 at risk EG0022 events1 affected41 at risk EG003
Foetal exposure during pregnancy	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Traumatic haemorrhage	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Wound	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Animal scratch	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Eyelid contusion	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Post-traumatic pain	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Scar	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Traumatic fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected41 at risk EG0011 events1 affected37 at risk EG0024 events4 affected41 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0013 events3 affected37 at risk EG0020 events0 affected41 at risk EG003
Weight decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0012 events2 affected37 at risk EG0020 events0 affected41 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Bacterial test positive	Investigations	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Blood cholesterol increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Blood glucose decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Cardiac murmur	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Coagulation time prolonged	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Crystal urine present	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Culture throat positive	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Haemoglobin urine present	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Monocyte count increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Monocyte percentage increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected41 at risk EG0010 events0 affected37 at risk EG0022 events1 affected41 at risk EG003
Neutrophil count increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Nitrite urine present	Investigations	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Platelet count increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Urine leukocyte esterase positive	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
White blood cell count decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected41 at risk EG0010 events0 affected37 at risk EG0022 events1 affected41 at risk EG003
White blood cell count increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Blood urea increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Cortisol decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Platelet count decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
White blood cells urine positive	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0012 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Prothrombin time prolonged	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Urine leukocyte esterase	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Left ventricular hypertrophy	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Normochromic normocytic anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Apnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Bronchial secretion retention	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 events1 affected41 at risk EG0010 events0 affected37 at risk EG0022 events1 affected41 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Choking	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Obstructive airways disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Pharyngeal erythema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Dystonia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG00011 events7 affected41 at risk EG0013 events3 affected37 at risk EG00210 events6 affected41 at risk EG003
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected41 at risk EG0013 events3 affected37 at risk EG0022 events2 affected41 at risk EG003
Oromandibular dystonia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0012 events2 affected37 at risk EG0021 events1 affected41 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Drooling	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected41 at risk EG0010 events0 affected37 at risk EG0022 events1 affected41 at risk EG003
Dyskinesia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Muscle spasticity	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Neuralgia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Migraine	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Nystagmus	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Sciatica	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Seizure	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Somnolence	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Multiple sclerosis	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Nerve compression	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Epilepsy	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Opisthotonus	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Parkinsonism	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Restless legs syndrome	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Hyperkinesia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Dark circles under eyes	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Eczema eyelids	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Optic atrophy	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Dry eye	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00011 events8 affected41 at risk EG0012 events2 affected37 at risk EG0025 events5 affected41 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0005 events5 affected41 at risk EG0011 events1 affected37 at risk EG0024 events4 affected41 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00012 events8 affected41 at risk EG0012 events2 affected37 at risk EG0028 events4 affected41 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0005 events4 affected41 at risk EG0012 events2 affected37 at risk EG0023 events3 affected41 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected41 at risk EG0010 events0 affected37 at risk EG0022 events2 affected41 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Faecaloma	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Faeces soft	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected41 at risk EG0010 events0 affected37 at risk EG0022 events1 affected41 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Haematemesis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Hyperchlorhydria	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Parotid gland enlargement	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Salivary hypersecretion	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Tongue disorder	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Gastrointestinal hypermotility	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Chromaturia	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Urine odour abnormal	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0004 events2 affected41 at risk EG0010 events0 affected37 at risk EG0023 events1 affected41 at risk EG003
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Product taste abnormal	Product Issues	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0022 events2 affected41 at risk EG003
Device failure	Product Issues	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Device occlusion	Product Issues	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Knee deformity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Osteopenia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Posture abnormal	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Secondary adrenocortical insufficiency	Endocrine disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0010 events0 affected37 at risk EG0022 events2 affected41 at risk EG003
Iron deficiency	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Ear infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected41 at risk EG0011 events1 affected37 at risk EG0023 events3 affected41 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0004 events3 affected41 at risk EG0011 events1 affected37 at risk EG0024 events3 affected41 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0007 events5 affected41 at risk EG0011 events1 affected37 at risk EG0024 events3 affected41 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0006 events6 affected41 at risk EG0012 events2 affected37 at risk EG0021 events1 affected41 at risk EG003
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0011 events1 affected37 at risk EG0022 events2 affected41 at risk EG003
Genital candidiasis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected41 at risk EG0010 events0 affected37 at risk EG0022 events2 affected41 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 events2 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Skin infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 events2 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0011 events1 affected37 at risk EG0021 events1 affected41 at risk EG003
Helminthic infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Oropharyngeal candidiasis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Stoma site infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003
Tooth infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Viral infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Vulvovaginal candidiasis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected41 at risk EG0010 events0 affected37 at risk EG0021 events1 affected41 at risk EG003
Cellulitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Pneumonia influenzal	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Rhinitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0011 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0012 events1 affected37 at risk EG0020 events0 affected41 at risk EG003
Ear lobe infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected41 at risk EG0010 events0 affected37 at risk EG0020 events0 affected41 at risk EG003

ID	Term
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D019150	Neuroaxonal Dystrophies
D009069	Movement Disorders
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Fosmetpantotenate	Double-blind Period: each randomized participant received an oral dose of fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants continued treatment with fosmetpantotenate according to the dose they were receiving at the end of the double-blind period. No dose escalation was required. Includes data over the entire study for those who completed the double-blind period and entered the open-label period.	1	41	9	41	35	41
EG001	Placebo	Double-blind Period: each randomized participant received an oral dose of placebo matched to fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks. Open-label Period: all participants started treatment with fosmetpantotenate according to the placebo dose they were receiving at the end of the double-blind period. No dose escalation was required. Includes data over the entire study for those who completed the double-blind period and entered the open-label period.	2	37	9	37	25	37
EG002	Fosmetpantotenate During Double-blind Period	Double-blind Period: each randomized participant received oral dose of fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks.	0	41	8	41	34	41
EG003	Placebo During Double-blind Period	Double-blind Period: each randomized participant received oral dose of placebo matched to fosmetpantotenate with dose escalation for Days 1 through 3, followed by the full dose TID from Day 4, based on the participant's age and weight at screening, for 24 weeks.	2	43	6	43	35	43
EG004	Fosmetpantotenate During Open-label Period	Open-label Period: at Week 25, all participants continued treatment with fosmetpantotenate according to the dose they were receiving at the end of the double-blind period. No dose escalation was required.	1	41	4	41	25	41
EG005	Placebo During Open-label Period	Open-label Period: at Week 25, all participants started treatment with fosmetpantotenate according to the placebo-matched dose they were receiving at the end of the double-blind period. No dose escalation was required.	0	37	9	37	26	37