Inclusion criteria

1. Signed Informed Consent

2. Males and females aged ≥18 years with a multi-system primary mitochondrial disease.

3. A confirmed mitochondrial DNA tRNALeu(UUR) m.3243A>G mutation (m.3243A>G PMD) plus
an age adjusted heteroplasmy percentage ≥ 20% in white blood cells [=blood
heteroplasmy/0.977(age+12)]. Or in urine (urinary epithelial cells), or buccal smear
or skeletal muscle (results (obtained per local guidance) ≥ 20% must be available
prior to the subject being randomized).

4. Presence of chronic fatigue (not attributable to other etiologies than PMD):

1. Patient self-reported chronic fatigue for at least 3 months prior to the
Screening Visit and recorded in the clinical patient files; AND

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

5. Presence of mitochondrial myopathy defined as:

5xSST at Screening and Baseline should be ≥ 11 seconds and participant must demonstrate
the ability to complete the test at baseline (i.e., complete the test within 30 seconds).

6. Other Inclusion criteria per protocol.

Exclusion criteria

1. Treatment with any IMP 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.

2. Bone deformities, motor abnormalities or chronic ulcers that in the opinion of the
PI may interfere with and/or confound the interpretation of the subject's
performance during the 5 times sit to stand test (5XSST).

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

4. Clinically significant respiratory disease and/or cardiac disease (medical history
or current clinical findings) in the opinion of the investigator.

5. Prior interventional cardiac procedure (e.g., cardiac catheterization,
angioplasty/percutaneous coronary intervention, balloon valvuloplasty, etc.) within
3 months prior to screening.

6. QTcF > 450 msec (men) or QTcF > 470 msec (women).

7. Structural heart disease based on cardiac MRI or Echocardiography (e.g., clinically
significant valve disease; i.e., aortic or mitral valve stenosis or regurgitation)
and/or abnormal conduction (QRS >120 msec, PR > 120 msec), and/or repolarization
(QTcF > 450 msec (men) or QTcF > 470 msec (women)). Myocardial function (LVEF <52%
in men and < 54% in women), symptomatic ischemic heart disease (inducible ischemia
or coronary obstruction), and/or pathologic hypertrophy (e.g. > 15mm septal or
posterior wall thickness), that is not well controlled under current specialized
care. Subjects with congestive heart failure class II and above should also be
excluded.

8. Family history of unexplained/uninvestigated syncope or congenital long and short QT
syndrome or sudden death (under the age of 60). ECG evidence of acute or recent
ischemia, acute or Recent Myocardial Infraction, atrial fibrillation, high grade AV
Blocks (Second Degree AV Block Type II or Third-degree AV Block), complete Heart
Block or active conduction system abnormalities with the exception of any of the
following:

1. First degree atrioventricular (AV)-block

2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type)

3. Right bundle branch block.

9. History of acute heart failure (within the last 3 months).

10. Higher degree of AV-blocks (AVB II° or III°).

11. Other exclusion criteria per protocol