Inclusion Criteria:

- Males and females aged ≥18 years.

- A confirmed mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation plus a heteroplasmy
percentage ≥ 20% in white blood cells, or urine (urinary epithelial cells), or
buccal smear or skeletal muscle (results must be available prior to the subject
being randomized).

- Presence of chronic fatigue (not attributable to otherwise treatable or reversible
etiologies):

- Complaints of patient self-reported chronic fatigue for at least 3 months prior
to the Screening Visit and recorded in the clinical patient files AND

- Presence of fatigue (raw total score >22 being a T-score >50), assessed by
Neuro-QoL SFv1-F at Screening.

- Presence of mitochondrial myopathy defined as:

- 5XSST at Screening and Baseline ≥ 9.1 seconds.

- Myopathy (proximal muscle weakness), NMDAS Section III Clinical Assessment at
Screening, item 5 score ≥1, which reads: "mild but clear proximal weakness in
hip flexion and shoulder abduction - MRC 4/5". For the inclusion only hip
flexion, but not shoulder abduction, should be taken into account.

- The patient is able and willing to provide written Informed Consent prior to
screening evaluations and to attend study appointments within the specified time
windows.

- The patient is, in the investigator's opinion, likely to comply with the protocol
and able to adhere to the study requirements for the length of the study, and
swallowing study medication, as well as the use of digital applications (ability to
complete electronic patient reported outcomes (PROs).

- Clinically stable (apart from PMD symptoms) at screening as determined by medical
history, physical examination, vital signs measurements, 12-lead ECG, and clinical
laboratory evaluations at Screening, and as assessed by the Investigator.

- The patient has been on stable exercise regimen for at least 4 weeks prior to
randomization and willing to not change their exercise regimen for the duration of
the study treatment period.

- Left Ventricular wall thickness ≤15 mm at screening if not explained by cardiac
involvement of mitochondrial disease (e.g., by cardiovascular magnetic resonance
[CMR]).

- Women of childbearing potential must be willing to use highly effective
contraceptive methods during the entire study. To be considered not of childbearing
potential, potential female participants must be post-menopausal for at least two
years, or have been surgically sterilised (bilateral tubal ligation, hysterectomy or
bilateral oophorectomy) for at least 6 months prior to Screening. Sonlicromanol has
been shown non-genotoxic judged from the Ames test, Chromosomal Aberration test and
in vivo Micronucleus test. Moreover, appreciable systemic exposure from the exposure
to (~2.5 mL) semen is extremely unlikely. However, until reproductive toxicology
studies have confirmed that sonlicromanol does not adversely affect normal
reproduction in adult males and females, as well as causing developmental toxicity
in the offspring, the following contraceptive precautions must be adhered to:

- Male subjects with female partners of childbearing potential must be willing to
use condoms during the entire study.

- Female partners of childbearing potential of male subjects must be willing to
use adequate contraceptive methods during the entire study, i.e., a hormonal
contraceptive method (pill, vaginal ring, patch, implant, injectable, hormone
medicated intrauterine device) or an intrauterine device.

Exclusion Criteria:

- Progressive External Ophthalmoplegia (PEO) as the single clinical manifestation
associated with m.3243A>G.

- Treatment with an IMP for PMD within 3 months (or 5 times the half-life of the IMP,
whichever is longer) prior to screening or plans to use an IMP (other than the study
intervention) during the study.

- Bone deformities or motor abnormalities of PMD or other than those related to
mitochondrial myopathy or significant other medical conditions that in the opinion
of the PI may interfere with and confound the interpretation the participant's
performance during the 5 times sit to stand test (5XSST).

- Surgery of gastrointestinal tract that might interfere with drug absorption. Or
severe GI dysmotility, chronic diarrhea, bouts of pseudo-obstruction which will
impair appropriate IMP absorption in the opinion of the investigator.

- Documented history of sustained ventricular tachycardia (HR >110 beats/min) at rest
and absence of an implanted cardioverter-defibrillator (ICD). In case of
non-sustained ventricular tachycardia, myocardial ischemia must be excluded.

- History of ischemic heart disease with reduced left ventricular ejection fraction
(<45%) and/or severe valvular heart disease.

- Symptomatic heart failure with reduced ejection-fraction with LVEF to 40% (HFrEF);
in case of heart failure with preserved ejection-fraction (HFpEF) or only mildly
reduced ejection-fraction (HFmrEF) (defined as LVEF ≥40%) patients may be included
if the clinical symptoms are stable for at least 3 months as judged by the
Investigator.

- History of acute heart failure (within the last 3 months), (family) history of
unexplained syncope or congenital long and short QT syndrome or sudden death.

- Higher degree of AV-blocks (AVB II° or III°) in the absence of a pacemaker or ICD.

- In case QTcFridericia is >450ms (male) and >470ms (female) and a simultaneous
bundle-branch-block (LBBB or RBBB) is not present at screening then QTcF will be
calculated using regular QT interval (three cycles averaged). In case LBBB or RBBB
is present, the modified QT interval (QTm) should be calculated by subtracting 50%
of the length of the BBB-QRS from the measured QT interval (QTm = QTBBB - 50%
QRSBBB). Subsequently, a rate-correction formula should be applied as usual. For
QTcF = QTm / (RR_Interval/1000)1/3.

- Novel and/or dynamic ECG abnormalities (including ST-segment elevation or depression
of >1 mm in at least two contiguous leads and/or T-wave inversions) within the last
3 months suggestive of myocardial ischemia. In this case the presence of myocardial
ischemia must be excluded to include the patient to this study.

- Recent history of unstable disease, inadequately controlled neurological
manifestations or not recovered from stroke-like episodes including but not limited
to stroke-like episodes within the last 6 months, hospitalized for status
epilepticus within the last 6 months.

- Blood pressure >160/90 mmHg at screening or baseline confirmed by re-testing (3x;
supine position; first measure after 20 minutes of rest).

- ≥1 clinical laboratory test value outside the reference range, based on the blood
and urine samples taken at the screening visit, that are of potential risk to the
patient's safety, or the patient has, at the screening visit:

- Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2.

- Serum potassium >5.0 mEq/L or <3.5 mEq/L).

- AST, ALT or total bilirubin (TBL) >3 x ULN at Screening. Patients who have a
slightly elevated TBL and/or ALT and/or AST and are suitable candidates for the
study, can be enrolled in the study if the Investigator can rule out any
underlying liver dysfunction by running additional tests and after discussing
the case with the medical monitor.

- Medical history of drug abuse (illegal drugs such as cannabinoids, amphetamines,
cocaine, opiates, or problematic use of prescription drugs such as benzodiazepines,
opiates).

- Within 4 weeks prior to screening, the use of:

- (multi)vitamins, co-enzyme Q10, Vitamin E, riboflavin, amino acids, and
antioxidant supplements (including, but not limited to idebenone/EPI-743, mitoQ
or alternative names for similar products); unless stable for at least one
month before screening and willing to remain stable throughout the study.

- any medication negatively influencing mitochondrial functioning (including but
not limited to valproic acid, glitazones, statins, anti-virals, amiodarone, and
non-steroidal anti-inflammatory drugs (NSAIDs)), unless the dose has been
stable for at least one month before screening and the dose is to remain stable
throughout the study (1).

- any strong Cytochrome P450 (CYP)3A4 inhibitors (all 'conazoles-anti-fungals',
HIV antivirals, grapefruit).

- strong CYP3A4 inducers (including HIV antivirals, carbamazepine, phenobarbital,
phenytoin, rifampicin, St. John's wort, pioglitazone, troglitazone).

- any medication metabolized by CYP3A4 with a narrow therapeutic index.

- medication known to be substrate of Organic Cation Transporter 1 (OCT1) and
organic cation transporter 2 (OCT2) with a narrow therapeutic index.

- strong P-glycoprotein inhibitors (including amiodarone, azithromycin,
captopril, clarithromycin, cyclosporine, piperine, quercetin, quinidine,
quinine, reserpine, ritonavir, tariquidar, and verapamil).

- any medication known to affect cardiac repolarisation unless QTcF interval at
screening is normal during stable treatment for a period of two weeks, or 5
half lives of the medication and its major metabolite(s), whichever period is
the shortest (all anti-psychotics, several anti-depressants, e.g.
nor-/amitriptyline, fluoxetine, anti-emetics: domperidone, granisetron,
ondansetron). For a complete list see https://crediblemeds.org.

- Patient has psychiatric conditions such as schizophrenia, bipolar disorder or major
depressive disorder that has not been under control within 3 months prior to
screening.

- Patient has severe behavioral or cognitive problems that preclude participation in
the study.

- Patient has undergone an inpatient hospitalization that precludes participation in
the study, within the 30 days prior to the randomization.

- Patient has a planned hospitalization or a surgical procedure during the study,
which may affect the study assessments.

- Patient has clinically significant and unstable respiratory disease and/or cardiac
disease (medical history or current clinical findings), or prior interventional
cardiac procedure (e.g., cardiac catheterization, angioplasty/percutaneous coronary
intervention, balloon valvuloplasty, etc.) within 3 months prior to randomization.

- Patient requires any ventilator support, including CPAP or BiPAP at night.

- Patient has severe vision impairment that may interfere with their ability to
complete all study requirements.

- Patient has an active malignancy or any other cancer from which the Patient has been
disease-free for <5 years, except for curative treated localized non-melanoma skin
cancer (e.g., basal cell or squamous cell carcinoma).

- Patient has a solid organ transplant and/or is currently receiving treatment with
therapy for immunosuppression.

- Patient has a history of active human immunodeficiency virus (HIV), hepatitis B or
hepatitis C infection.

- The patient has an immediate family member (defined as family members residing at
the same address) who participates in the study or the continuation protocol (to
avoid potential mix up / switch of medications during participation).

- Patient has BMI below 18.5 kg/m2 or above 35 kg/m2 at screening.

- Patient has any active viral or bacterial infection at the time of randomization.

- Patient is pregnant or breast feeding.