TaRGET

Inclusion

• Age ≥ 18 years
• A pathogenic or likely pathogenic desmosomal (PKP2, DSG2, DSC2, DSP, or JUP*) rare variant OR the TMEM43-p.S358L variant
• Mean ≥ 500 PVCs per 24 hours on a baseline screening 7-day Holter monitor.
• Clinical ACM diagnosis or recognition of genetic carrier status for ≥ 6 months prior to screening.

*JUP carriers must be homozygous or compound heterozygous

Exclusion

• NYHA class IV heart failure
• Ventricular scar secondary to coronary artery disease
• Initiation, cessation, or dose change of a Class I or III antiarrhythmic drug in the 3 months prior to screening
• Any potentially harmful chronic liver disease
• ALT value > 2X the upper limit of the normal reference range at screening
  Total bilirubin value greater than the upper limit of the normal reference range at Screening, unless documented Gilbert’s syndrome. For individuals with Gilbert’s syndrome, total bilirubin value greater than 2-fold the upper limit of the normal reference range at screening.
• A history of alcohol or illicit substance use disorders
• Regular and long-term use of strong CYP3A4 inhibitors, including clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir
• Serum creatinine > 150 micromole/L or creatinine clearance ≤ 60 mL/min (according to Cockcroft-Gault formula) at screening
• Pregnant at time of enrollment and women of childbearing age who do not use a highly effective form of contraception
• Males, engaged in sexual relations with a female of child-bearing potential, not using an acceptable contraceptive method if not surgically sterile
• Patients unwilling to provide informed consent or comply with follow-up
• Hypersensitivity to tideglusib or any components of its formulation, including allergy to strawberry
• Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window e.g. warfarin and digoxin