This trial is conducted in patients with an inherited heart rhythm disorder called catecholaminergic polymorphic ventricular tachycardia (CPVT). This condition causes the heart to beat dangerously fast during situations of physical or emotional stress. CPVT is a serious condition that can limit the length and quality of patients' lives. Current treatment does not always prevent the abnormal heart rhythms that can occur as part of CPVT during strenuous exercise or stress, so new and improved medications are needed.
The main questions that the trial will answer are:
* How safe and tolerable is the drug AGP100; i.e, what medical problems do patients experience when taking the drug? * Does the drug help CPVT patients to maintain a normal heart rhythm while they are exercising? * How does the drug affect the levels of key heart cell signalling molecules?
Patients with a diagnosis of CPVT who are aged between 18 and 75 and experience abnormal heart rhythms during exercise, despite taking a stable dose of the medication(s) prescribed by their doctor for their CPVT can take part in this trial. Participants should have normal kidney and liver function and not have high blood pressure or a diagnosis of structural heart disease. Women who are pregnant or breastfeeding cannot take part in the study. Participants who may become pregnant (and their partners) need to use highly effective methods of contraception during the study and for 90 days after the study ends.
Participants will take part in the study for ten weeks. During this time, participants will be asked to take three different doses of the the drug (AGP100), as well as their normal heart medication. The drug is an oral capsule and each different dose will be taken once a day for 13 days. The study starts with participants taking a low dose for 2 weeks, then a medium dose and then a high dose. At each dose, participants will undergo a clinical examination, report any potential side effects and the treating doctor will investigate the safety, tolerability and side effects of AGP100. In total, participants will take AGP100 once a day for about six weeks. The last four weeks of the study will be a follow-up period where participants will not take AGP100.
During the study, participants will need to visit the hospital six times. The visits will be three outpatient appointments and three overnight stays.
Signed informed consent prior to any study-related procedures
Male or female, aged between 18 and 75 years (inclusive)
Clinical diagnosis of CPVT based on proven RYR2 mutation AND reproducible premature ventricular contraction with exercise or polymorphic or bidirectional ventricular tachycardia with exercise
Able and willing to undergo exercise testing (bicycle test) AND exhibits exercise-induced ventricular ectopic beats at Screening (at least 1 point on the VA scale)
Diagnosis of structural heart disease, including coronary artery disease or heart failure with reduced ejection fraction (left ventricular ejection fraction <45%)
Participants who have had arrhythmias causing hemodynamic instability at previous exercise tests (performed while on the current standard of care treatment)
Participants having a sustained VT (VA score of 5) during the exercise tests performed as part of the screening activities
Participation in another clinical study with an investigational product or device within 60 days of 5 half-lives prior to Baseline (whichever is longer)
Single group
AGP100
DrugAGP100 is a capsule for oral administration. The drug substance is formulated as an encapsulated dry powder blend composed of 5 mg or 25 mg active ingredient and inactive excipients filled into a white, opaque, size 3 hard gelatine capsule. The drug product is a white to light brown solid, with low solubility in water. During study visits, participants will take IMP under supervision of the study staff. Participants will receive with the oral dose together with water. During the rest of each treatment period, participants will self-administer the IMP. Doses should be taken with water, as needed. Participants are to continue to take the IMP once per day until they attend the study visit that starts the next treatment period/the end of study visit.
Incidence of adverse events (AEs)
Changes in heart rate (HR)
Unit: beats per minute (bpm)
Changes in 12-lead electrocardiogram parameters: estimated ventricular frequency
Unit: bpm
Changes in 12-lead electrocardiogram parameters: PR
Unit: milliseconds (ms)
Change from baseline in the amount and complexity of exercise-induced ventricular ectopic beats as assessed using the ventricular arrythmia (VA) score
The VA score is reported as an ordinal value on a scale from 0 to 5. 0 = no inducible VA, 1 = isolated inducible premature ventricular contractions (PVCs); \<10 beats per minute, 2 = bigeminal PVCs and/or frequent PVCs (≥10 per minute), 3 = ventricular couplet, 4 = non-sustained ventricular tachycardia (VT) (≥3 consecutive PVCs at a rate of \>100 beats per minute \[bpm\], terminating spontaneously), 5 = sustained VT (≥30 seconds and rate \>100 bpm) or ventricular fibrillation
Change from baseline in urine cyclic guanosine monophosphate (cGMP) levels
Change from baseline in urine cyclic adenosine monophosphate (cAMP) levels
Change from baseline in plasma cGMP levels
Click on the lead sponsor to view all of their trials.
Agiana Pharmaceuticals
Lead sponsor
Link Medical Research AS
Collaborator
Viedoc Technologies AB
Collaborator
Vitas AS
Collaborator
