A Study to Assess the Efficacy and Safety of Vatiquinone... | NCT04577352

Label	Type	Description	Intervention Names
Vatiquinone	Experimental	Participants will receive vatiquinone capsule at a dose of either 200 milligrams (mg) orally 3 times a day (TID) if ˂12 years of age and weighing ˂25 kilograms (kg) or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the placebo-controlled phase and for 24 weeks during the open-label extension phase.	Drug: Vatiquinone
Placebo	Placebo Comparator	Participants will receive placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the placebo-controlled phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label extension phase.	Drug: Vatiquinone Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Vatiquinone	Drug	Vatiquinone will be administered per dose and schedule specified in the arm.	Placebo Vatiquinone

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the mFARS Score at Week 72 - Modified Intent-to-treat (mITT) Analysis Set	mFARS is a 93-item scale; comprised of neurologic component of FARS. For each item, responses categorize the corresponding neurological finding, with a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment. Total mFARS scores for each subscale: bulbar (0 to 5), upper limb coordination (0 to 36), lower limb coordination (0 to 16), and upright stability (0 to 36). mFARS total score was a composite score of all 4 subscales, ranging from 0 (normal) to 93 (greater impairment). A lower score = better neurological function. Missing data was imputed using pattern mix model multiple imputation. Least square (LS) mean and standard error (SE) was calculated using mixed-model repeated measures (MMRM).	Baseline, Week 72
Change From Baseline in the mFARS Score at Week 72 - Intent-to-treat (ITT) Analysis Set	mFARS is a 93-item scale; comprised of neurologic component of FARS. For each item, responses categorize the corresponding neurological finding, with a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment. Total mFARS scores for each subscale: bulbar (0 to 5), upper limb coordination (0 to 36), lower limb coordination (0 to 16), and upright stability (0 to 36). mFARS total score was a composite score of all 4 subscales, ranging from 0 (normal) to 93 (greater impairment). A lower score = better neurological function. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.	Baseline, Week 72

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Friedreich Ataxia Rating Scale Activities of Daily Living (FARS-ADL) Score at Week 72 - mITT Analysis Set	The ADL component of the FARS includes 9 subscales: speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function. Each of these subscales is rated on a 5-point scale where 0=normal to 4=severe disability/inability to carry out activity independently for a total possible score of 0 to 36, with higher scores representing greater disability/dependency. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.

Other Outcomes

Measure	Description	Time Frame
Change From Baseline in the Upright Stability Subscale of the mFARS at Week 72 - mITT Analysis Set	mFARS is a 93-item scale; comprised of neurologic component of FARS. For each item, responses categorize the corresponding neurological finding, with a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment. The Upright Stability subscale of the mFARS includes following items: 1. Sitting posture (score: 0 to 4); 2a. Stance with feet apart and eyes open (score: 0 to 4); 2b. Stance with feet apart and eyes closed (score: 0 to 4); 3a. Stance with feet together and eyes open (score: 0 to 4); 3b. Stance with feet together and eyes closed (score: 0 to 4); 4. Tandem stance (score: 0 to 4); 5. Stance on dominant foot (score: 0 to 4); 6. Tandem walk (score: 0 to 3); 7. Gait (score: 0 to 5). The upright stability subscale total score ranges from 0 (normal) to 36 (greater impairment). A lower score = better neurological function. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

mFARS ≥20 to ≤70 at baseline
Must be able to ambulate at least 10 feet in 1 minute with or without assistance (non-wheelchair).
Friedreich ataxia diagnosis (homozygous for guanine-adenine-adenine [GAA] repeat expansion in intron-1 of frataxin [FXN] gene), confirmed by clinical testing (Note: size of GAA repeat is not required for eligibility)
Consent to comply with study procedures. For participants under the age of 18 (or age of consent), parent(s)/legal guardian(s) of the participant must agree to comply with the requirements of the study, including the need for frequent and prolonged follow up; parent(s)/legal guardian(s) with custody of the participant must give their consent for participant to enroll in the study.
Difference in the mFARS at screening and baseline of no more than 4 points.
Must be able to abstain from anticoagulants and any aspirin (including 81 mg) for 30 days prior to the baseline visit and for the duration of the study; any possible discontinuation of anticoagulants should be monitored and indicated by a specialist (for example, cardiologist, neurologist, or hematologist) and discontinuation will be noted by the prescribing physician.
Must be able to abstain from potent cytochrome P450 (CYP) 3A4 inducers/inhibitors (for example, ketoconazole, rifampin, St. John's wort, grapefruit juice or any grapefruit product) for at least 30 days prior to enrollment
Must be able to swallow capsules
Males and females of childbearing potential must be willing to use an effective method of contraception from the time consent is signed until 30 days after the last dose of study drug or early termination visit. Male participants must agree not to donate sperm during the study and for at least 30 days after the last dose of study drug or early termination visit.

Exclusion Criteria:

Individuals with clinical diagnosis of FA who have point mutations or deletions or other non-GAA expansion mutations
Previous treatment with vatiquinone
Allergy to vatiquinone, sesame oil, gelatin (bovine and/or porcine), titanium dioxide, or red iron oxide
Ejection fraction <50%
Uncontrolled diabetes (glycated hemoglobin [HbA1c] >7.0%) at the time of screening
Has current suicidal ideation based on Columbia-Suicide Severity Rating Scale (C-SSRS) within 3 months prior to screening or between screening and baseline at the baseline visit or suicidal behavior within the last year at the screening visit or between screening and baseline at the baseline visit
Pregnant or lactating participants or those sexually active participants who are unwilling to comply with proper birth control methods; females of childbearing potential must have a negative pregnancy test at screening and during the baseline visit
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2 * upper limit of normal (ULN) at time of screening
International normalized ratio (INR) ≥1.5 * ULN at time of screening or clinically significant (CS) bleeding, as determined by the investigator
Serum creatinine ≥1.5 * ULN at time of screening
Comorbidities that may confound study results (for example, fat malabsorption syndrome, other mitochondrial disorder) in the opinion of the investigator
Participation in any other interventional clinical trial or received any investigational drug in any other clinical trial within 60 days prior to the baseline visit. Participants may be rescreened after the exclusionary period of 60 days has passed.
Concomitant use of interventional coenzyme Q10 (CoQ10), vitamin E, or any approved or non-approved medication for FA within 30 days prior to the screening visit. These prohibited medications can be discontinued at the screening visit; if this is the case, the mFARS assessment must be repeated to confirm inclusion eligibility after a minimum of 30 days post-discontinuation and there must be no more than a 4-point difference in mFARS assessed from the post-discontinuation visit to the baseline visit.
Illicit drug use 30 days prior to screening and during the study is prohibited.

Facility	Status	City	State	ZIP	Country	Contacts
UCLA		Los Angeles	California	90095	United States
University of Florida

ID	Title	Description
FG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 milligrams (mg) orally 3 times a day (TID) if ˂12 years of age and weighing ˂25 kilograms (kg) or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 21, 2021	Mar 19, 2026

ID	Title	Description
BG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
BG001	Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0001.218± 0.9652(0.9652 to ) OG0012.828± 0.9994(0.9994 to )

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		= 0.1440		LS Mean Difference	-1.610	Standard Error of the Mean	1.1016	2-Sided	95	-3.769	0.550					Other

Primary

Change From Baseline in the mFARS Score at Week 72 - Intent-to-treat (ITT) Analysis Set

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.

Secondary

Change From Baseline in Friedreich Ataxia Rating Scale Activities of Daily Living (FARS-ADL) Score at Week 72 - mITT Analysis Set

The ADL component of the FARS includes 9 subscales: speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function. Each of these subscales is rated on a 5-point scale where 0=normal to 4=severe disability/inability to carry out activity independently for a total possible score of 0 to 36, with higher scores representing greater disability/dependency. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.

Secondary

Change From Baseline in FARS-ADL Score at Week 72 - ITT Analysis Set

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.

Secondary

Change From Baseline in 1-Minute Walk Test (1MWT) at Week 72 - mITT Analysis Set

The 1MWT is a timed performance test used to measure functional ability, walking endurance, balance, and muscle performance by measuring maximal walking speed in 1 minute. Participants were instructed to walk as quickly as possible for 1 minute without running. Maximal walking speed was measured upon completion of the walk and distance was recorded. The mean change from baseline in the distance the participant walked is reported. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.

Posted

Least Squares Mean

Standard Error

meters

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.

Secondary

Change From Baseline in 1MWT at Week 72 - ITT Analysis Set

Posted

Least Squares Mean

Standard Error

meters

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.

Secondary

Number of Falls Per 28 Days Over Every 24-Week Period - mITT Analysis Set

Each participant was required to maintain a fall log, which included the date and time of each fall. Falls as defined by World Health Organization as "inadvertently coming to rest on the ground, floor or other lower level, excluding intentional change in position to rest in furniture, wall or other objects," were reported. Number of falls per 28 days during a time interval was calculated as the number of falls during the period divided by the number of days during the interval, and multiplied by 28. The falls that occurred on or after the first Loss of Ambulation visit were excluded from the analysis.

The mITT analysis set included all randomized participants, between age of 7 and 21 years, inclusive, at Screening, had received at least 1 dose of study drug (vatiquinone or placebo), had baseline and at least 1 post-baseline measurement of the primary endpoint. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable at specified timepoint.

Posted

Mean

Standard Deviation

falls

Week 1-24, Week 25-48, and Week 49-72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo

Secondary

Number of Falls Per 28 Days Over Every 24-Week Period - ITT Analysis Set

The ITT analysis set included all randomized participants who had received at least 1 dose of study drug (vatiquinone or placebo), and had baseline and at least 1 postbaseline measurement of the primary endpoint. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable at specified timepoint.

Posted

Mean

Standard Deviation

falls

Week 1-24, Week 25-48, and Week 49-72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo

Other Pre-specified

Change From Baseline in the Upright Stability Subscale of the mFARS at Week 72 - mITT Analysis Set

mFARS is a 93-item scale; comprised of neurologic component of FARS. For each item, responses categorize the corresponding neurological finding, with a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment. The Upright Stability subscale of the mFARS includes following items: 1. Sitting posture (score: 0 to 4); 2a. Stance with feet apart and eyes open (score: 0 to 4); 2b. Stance with feet apart and eyes closed (score: 0 to 4); 3a. Stance with feet together and eyes open (score: 0 to 4); 3b. Stance with feet together and eyes closed (score: 0 to 4); 4. Tandem stance (score: 0 to 4); 5. Stance on dominant foot (score: 0 to 4); 6. Tandem walk (score: 0 to 3); 7. Gait (score: 0 to 5). The upright stability subscale total score ranges from 0 (normal) to 36 (greater impairment). A lower score = better neurological function. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.

Other Pre-specified

Change From Baseline in the Upright Stability Subscale of the mFARS at Week 72 - ITT Analysis Set

mFARS is a 93-item scale; comprised of neurologic component of FARS. For each item, responses categorize the corresponding neurological finding, with a score ranging from 0 to 3, 4, or 5 with 0 being normal and higher numbers indicative of greater impairment. The Upright Stability subscale of the mFARS includes following items: 1. Sitting posture (score: 0 to 4); 2a. Stance with feet apart and eyes open (score: 0 to 4); 2b. Stance with feet apart and eyes closed (score: 0 to 4); 3a. Stance with feet together and eyes open (score: 0 to 4); 3b. Stance with feet together and eyes closed (score: 0 to 4); 4. Tandem stance (score: 0 to 4); 5. Stance on dominant foot (score: 0 to 4); 6. Tandem walk (score: 0 to 3); 7. Gait (score: 0 to 5). The upright stability subscale total score ranges from 0 (normal) to 36 (greater impairment). A lower score = better neurological function. Missing data was imputed using pattern mix model multiple imputation. LS mean and SE was calculated using MMRM.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.

Other Pre-specified

Change From Baseline in the Modified Fatigue Impact Scale (MFIS) Score at Week 72 - mITT Analysis Set

The MFIS is a 21-item, reliable, validated instrument that has been utilized in many neurological disorders. It is a modified form of the Fatigue Impact Scale, a component of the Multiple Sclerosis Quality of Life Inventory. Each item was scored on a scale of 0 (never) to 4 (almost always). The total score was the sum of all item's score and ranged from 0 (no fatigue impact) to 84 (almost always impacted by fatigue). Higher scores indicated greater impact of fatigue on participant function.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.

Other Pre-specified

Change From Baseline in the MFIS Score at Week 72 - ITT Analysis Set

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, Week 72

ID	Title	Description
OG000	Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase and for 24 weeks during the open-label phase.
OG001	Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase and vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Myocarditis	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0011 events1 affected73 at risk EG0021 events1 affected73 at risk EG0030 events0 affected65 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0012 events1 affected73 at risk EG0020 events0 affected73 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected73 at risk EG0020 events0 affected73 at risk EG003
Multisystem inflammatory syndrome in children	Immune system disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected73 at risk EG0020 events0 affected73 at risk EG003
Appendicitis perforated	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Intentional product misuse	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected73 at risk EG0020 events0 affected73 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected73 at risk EG0020 events0 affected73 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Seizure	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected73 at risk EG0020 events0 affected73 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Completed suicide	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0011 events1 affected73 at risk EG0020 events0 affected73 at risk EG003
Depression	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0010 events0 affected73 at risk EG0022 events2 affected73 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected73 at risk EG0020 events0 affected73 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected73 at risk EG0020 events0 affected73 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected73 at risk EG0020 events0 affected73 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected73 at risk EG0020 events0 affected73 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected73 at risk EG0021 events1 affected73 at risk EG003
Presyncope	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0010 events0 affected73 at risk EG0020 events0 affected73 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Tachycardia	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 events1 affected73 at risk EG0016 events4 affected73 at risk EG0021 events1 affected73 at risk EG0030 events0 affected65 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00015 events10 affected73 at risk EG0017 events6 affected73 at risk EG00215 events10 affected73 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0009 events7 affected73 at risk EG00117 events10 affected73 at risk EG00211 events8 affected73 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00028 events19 affected73 at risk EG00112 events10 affected73 at risk EG00231 events21 affected73 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0008 events4 affected73 at risk EG0013 events3 affected73 at risk EG00210 events5 affected73 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00016 events13 affected73 at risk EG00116 events10 affected73 at risk EG00219 events15 affected73 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected73 at risk EG0015 events4 affected73 at risk EG0022 events2 affected73 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG00017 events14 affected73 at risk EG00113 events9 affected73 at risk EG00221 events17 affected73 at risk EG003
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment	EG00012 events9 affected73 at risk EG00121 events13 affected73 at risk EG00214 events11 affected73 at risk EG003
Pyrexia	General disorders	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected73 at risk EG00114 events9 affected73 at risk EG0025 events5 affected73 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00036 events32 affected73 at risk EG00126 events24 affected73 at risk EG00241 events36 affected73 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected73 at risk EG0014 events4 affected73 at risk EG0024 events4 affected73 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0005 events5 affected73 at risk EG0015 events4 affected73 at risk EG0025 events5 affected73 at risk EG003
Influenza	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0009 events8 affected73 at risk EG00113 events11 affected73 at risk EG00210 events9 affected73 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00019 events12 affected73 at risk EG00134 events17 affected73 at risk EG00220 events12 affected73 at risk EG003
Sinusitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0005 events4 affected73 at risk EG0012 events2 affected73 at risk EG0025 events4 affected73 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00017 events9 affected73 at risk EG00110 events8 affected73 at risk EG00224 events12 affected73 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected73 at risk EG0014 events2 affected73 at risk EG0026 events6 affected73 at risk EG003
Viral infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected73 at risk EG0011 events1 affected73 at risk EG0024 events4 affected73 at risk EG003
Viral rhinitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG00018 events8 affected73 at risk EG0014 events3 affected73 at risk EG00224 events11 affected73 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected73 at risk EG0012 events2 affected73 at risk EG0024 events4 affected73 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected73 at risk EG0016 events6 affected73 at risk EG0022 events2 affected73 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG000363 events58 affected73 at risk EG001441 events61 affected73 at risk EG002468 events59 affected73 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected73 at risk EG0015 events5 affected73 at risk EG0024 events4 affected73 at risk EG003
International normalised ratio increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected73 at risk EG0010 events0 affected73 at risk EG0024 events4 affected73 at risk EG003
Weight increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 events0 affected73 at risk EG0016 events6 affected73 at risk EG0021 events1 affected73 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0006 events5 affected73 at risk EG0013 events3 affected73 at risk EG0026 events5 affected73 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0007 events6 affected73 at risk EG0011 events1 affected73 at risk EG0029 events7 affected73 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0008 events7 affected73 at risk EG0018 events6 affected73 at risk EG00214 events9 affected73 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected73 at risk EG0017 events6 affected73 at risk EG0024 events4 affected73 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected73 at risk EG0014 events4 affected73 at risk EG0023 events3 affected73 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.0	Systematic Assessment	EG00011 events9 affected73 at risk EG00110 events7 affected73 at risk EG00211 events9 affected73 at risk EG003
Balance disorder	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0002 events2 affected73 at risk EG0014 events4 affected73 at risk EG0022 events2 affected73 at risk EG003
Dizziness	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00015 events11 affected73 at risk EG0018 events8 affected73 at risk EG00218 events12 affected73 at risk EG003
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG00037 events22 affected73 at risk EG00153 events26 affected73 at risk EG00243 events25 affected73 at risk EG003
Syncope	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected73 at risk EG0011 events1 affected73 at risk EG0024 events4 affected73 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 26.0	Systematic Assessment	EG0005 events5 affected73 at risk EG0015 events3 affected73 at risk EG0026 events6 affected73 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0009 events4 affected73 at risk EG0018 events3 affected73 at risk EG0029 events4 affected73 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0005 events5 affected73 at risk EG0016 events6 affected73 at risk EG0025 events5 affected73 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0008 events6 affected73 at risk EG0014 events3 affected73 at risk EG00210 events8 affected73 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG00011 events8 affected73 at risk EG00111 events8 affected73 at risk EG00211 events8 affected73 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected73 at risk EG0012 events2 affected73 at risk EG0024 events4 affected73 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0004 events3 affected73 at risk EG0013 events3 affected73 at risk EG0026 events4 affected73 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0003 events3 affected73 at risk EG0011 events1 affected73 at risk EG0025 events5 affected73 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.0	Systematic Assessment	EG0004 events4 affected73 at risk EG0016 events5 affected73 at risk EG0027 events5 affected73 at risk EG003

ID	Term
D013132	Spinocerebellar Degenerations
D002526	Cerebellar Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D013118	Spinal Cord Diseases
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D028361	Mitochondrial Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Double-blind Phase: Vatiquinone	Participants received vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 72 weeks during the double-blind phase.	1	73	8	73	71	73
EG001	Double-blind Phase: Placebo	Participants received placebo matching to vatiquinone (per age and weight) orally TID for 72 weeks during the double-blind phase.	1	73	8	73	73	73
EG002	On-Vatiquinone Period: Vatiquinone/Vatiquinone	Participants who received vatiquinone for 72 weeks in the double-blind phase continued to receive vatiquinone capsule at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.	1	73	10	73	71	73
EG003	On-Vatiquinone Period: Placebo/Vatiquinone	Participants who received placebo for 72 weeks in the double-blind phase, received vatiquinone at a dose of either 200 mg orally TID if ˂12 years of age and weighing ˂25 kg or 400 mg orally TID if ≥12 years of age and/or weighing ≥25 kg for 24 weeks during the open-label phase.	0	65	2	65	53	65