A Phase II, Double-Blind 2-arm study to investigate the effect on ventricular ectopy, safety, tolerability and pharmacokinetics of S48168 (ARM210) compared with Placebo in adults with Type 1 Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT1)

Participants are eligible to be included in the study only if all the following
criteria apply: Age 1. Participant must be at least 18 years of age inclusive,
at the time of signing the informed consent Type of Participant and Disease
Characteristics 2. Participants who are willing and able to comply with
scheduled visits, study drug administration plan, study restrictions, and study
procedures. 3. Participants have a confirmed genetic diagnosis of CPVT1 and
supporting clinical phenotype, including residual ventricular ectopy (a
complexity score >=2; requiring at minimum the presence of PVCs in bigeminy on
exercise stress test) on a stable (at least 1 month) standard-of-care,
CPVT1-directed treatment regimen as decided by their CPVT treating physician.
Weight 4. Have a body mass index (BMI) <= 38 kg/m2 (inclusive) at screening. Sex
and Contraceptive/Barrier Requirements 5. Male participants agree to not donate
sperm from the first day of dosing of study drug until 5 half-lives plus 90
days (approximately 94 days) after the last dose of study drug. Female
participants: eligible to participate if she is not pregnant or breastfeeding,
and uses one of the following highly effective birth control methods (from the
first dose until 5 half-lives plus 90 days (approximately 94 days): •
Prescribed hormonal oral contraceptives, vaginal ring, or transdermal patch. •
Intrauterine device (IUD). • Intrauterine hormone-releasing system (IUS). •
Depot/implantable hormone (e.g., Depo-Provera®, Implanon). • Bilateral tubal
occlusion/ligation. • Sexual abstinence. • Refraining from heterosexual
intercourse during the entire period of risk associated with the study
requirements. • If the participant decides to become sexually active during the
study, then one of the highly effective birth control methods must be used. OR
Is a woman of non-childbearing potential; defined by at least 1 of the
following criteria: • Postmenopausal defined as 12 months of spontaneous
amenorrhea without a medical cause and follicle stimulating hormone (FSH) serum
level > 40mIU/mL without the use of hormonal supplementation. Appropriated
documentation of FSH levels is required. • Surgically sterile by hysterectomy
and/or bilateral oophorectomy with appropriate documentation of surgical
procedure. • Has a congenital condition resulting in no uterus. Informed
Consent 6. Capable of giving signed informed consent as described in Appendix 1
which includes compliance with the requirements and restrictions listed in the
informed consent form (ICF) and in this protocol.

Participants are excluded from the study if any of the following criteria
apply: Medical Conditions 1. History or presence of alcoholism or drug abuse
within the past 2 years prior to the first dose of study drug. 2. History or
presence of hypersensitivity or idiosyncratic reaction to the study drug,
related compounds, or inactive ingredients. 3. ALT or AST levels three times
above the upper limits of normal (ULN) at screening (isolated elevations of
total bilirubin < 2 X ULN with direct bilirubin below the ULN will be
included). A recheck for confirmation is allowed. 4. History of documented,
EEG-confirmed epileptic seizures. 5. History of cancer (malignancy).
Exceptions: (1) Subjects with adequately treated non-melanomatous carcinoma or
carcinoma in situ of the cervix may participate in the trial (2) Subjects with
other malignancies who have been successfully treated >10years prior to the
screening where in the judgment of the investigator has revealed no evidence of
recurrence from the time of treatment through the time of the screening except
those identified at the beginning of the exclusion criterion or (3) Subjects
who in the opinion of the investigator are highly unlikely to sustain a
recurrence for the duration of the trial. 6. Currently has uncontrolled
diabetes defined as HbA1c > 8% at screening visit or diabetic neuropathy. 7.
Estimated creatinine clearance < 40mL/minute at screening visit. 8. Clinically
significant abnormality on their screening and/or prior to first dosing resting
ECG, other than hypertensive related, or heart failure (ejection fraction <
30%) or other clinically significant structural heart disease. 9. History of
myocardial infarction in the last five years, or evidence of congestive heart
failure. 10. Ongoing medical condition that is deemed by the PI to interfere
with the conduct or assessments of the study or safety of the subject.
Prior/Concomitant Therapy 11. Unable to refrain from or anticipates the use of:
• Any non-approved medicines (prescribed standard-of-care for CPVT is approved)
and/or dietary supplements beginning 14 days prior to the first dose of study
drug and throughout the study. Thyroid hormone replacement medication may be
permitted if subject has been on same stable dose for the last 3 months prior
to the first dose of study drug. • Any drugs known to be significant inducers
or inhibitors of CYP2C8 enzymes for 28 days prior to the first dose of study
drug and throughout the study. Is currently taking any drug which raises
gastric pH, including proton pump inhibitors or H2 antagonists. Antacids may be
used if taken greater than 6 hours after study drug and/or at night.
Prior/Concurrent Clinical Study Experience 12. Participation in clinical trials
for other therapeutic investigational drugs simultaneously or within the 4
weeks prior to the first dose of study drug. Diagnostic Assessments 13. Plasma
donation within 7 days prior to the first dose of study drug. 14. Donation of
blood or significant blood loss within 56 days prior to the first dose of study
drug. Other Exclusion Criteria 15. Is mentally or legally incapacitated at the
time of screening visit. 16. Is unable to take orally administered tablets. 17.
Is an immediate family member of the Sponsor or employee of the clinical site
or may consent under duress.