Verapamil hydrochloride for Type 1 diabetes mellitus

Inclusion criteria

• {"criterion_text":"-Be either eligible for Visit 6 of Ver-A-T1D trial on active treatment defined as Placebo or Verapamil SR (240 mg or 360 mg) (option 1) OR have completed V5 of the Ver-A-T1D study and plan to continue with Ver-AT1D Visit 6 on active treatment defined as Placebo or Verapamil SR (240mg or 360mg) up to 28 days prior to Ver-A-T1D Visit 6 (option 2)"}
• {"criterion_text":"-Have given written informed consent (Ver-A-Long)."}
• {"criterion_text":"-Age ≥18 years at consent."}
• {"criterion_text":"-Must have fasting C-peptide levels ≥50 pmol/L measured at V-1 (according to option 1) or measured at V-2 (according to option 2)."}

Exclusion criteria

• {"criterion_text":"-Be currently pregnant, lactating or anticipate getting pregnant during the 24 months study period."}
• {"criterion_text":"-Substrate intake of CYP3A4 and/or glycoprotein-P metolism, as judged by the investigator"}
• {"criterion_text":"-Hypotension (of less than 90 mmHg systolic), sick sinus syndrome (except patients with a functioning artificial pacemaker), uncompensated heart failure or severe left ventricular dysfunction, marked bradycardia (less than 45 beats/minute), atrioventricular block second or third degree, atrial flutter or atrial fibrillation in the presence of an accessory bypass tract (e.g. Wolff-Parkinson-White syndrome), hypertrophic cardiomyopathy, acute myocardial infarction, attenuated neuromuscular transmission (e.g. by myasthenia gravis, Lambert-Eaton syndrome, advanced Duchenne muscular dystrophy)."}
• {"criterion_text":"-Atrioventricular block first degree (>320ms)."}
• {"criterion_text":"-Current use of ß-blockers."}
• {"criterion_text":"-Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results."}
• {"criterion_text":"-Have any complicating medical issues or history that may interfere with the study conduct, as judged by the investigator."}
• {"criterion_text":"-Have persistent history of malignancies other than skin."}
• {"criterion_text":"-History of liver insufficiency or laboratory evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal."}
• {"criterion_text":"-History of renal insufficiency or evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal."}
• {"criterion_text":"-Current use of calcium channel blockers (except IMP administrated in the Ver-A-T1D trial)."}
• {"criterion_text":"-Known hypersensitivity to Verapamil SR or to any of its excipients."}
• {"criterion_text":"-Concomitant medication known for inducing or inhibiting CYP3A4 and/or glycoprotein-P metabolism."}
• {"criterion_text":"-Intake of grapefruit juice, licorice, St. John’s Wort, cannabidiol, ginkgo biloba."}

Primary endpoints

• {"endpoint_text":"-Change over time in C-peptide Area under the curve (C-pep AUC % change) in adults diagnosed with T1D receiving 360 mg oral Verapamil daily undergoing MMTT, measured at baseline (V-1) and 24 months of therapy (V8)","definition_or_measurement_approach":"Measured as percentage change in C-peptide area under the curve (C-pep AUC %) during a mixed-meal tolerance test (MMTT) at baseline (V-1) and after 24 months of therapy (V8) for adults receiving 360 mg oral Verapamil once daily."}

Secondary endpoints

• {"endpoint_text":"-Changes over time in C-peptide Area under the curve (C-pep AUC % change) in adults diagnosed with T1D receiving 360 mg oral Verapamil daily undergoing MMTT, measured at 6-, 12-, and 18 months of therapy (V5 to V7)","definition_or_measurement_approach":"Measured as percentage change in C-peptide AUC during MMTT at 6, 12 and 18 months for adults on 360 mg oral Verapamil once daily."}
• {"endpoint_text":"-Changes over time in blood glucose control as assessed by HbA1C in adults diagnosed with T1D receiving 360 mg oral Verapamil daily, measured at baseline (V-1) and 6-, 12-, 18- and 24 months of therapy (V5 to V8)","definition_or_measurement_approach":"Measured HbA1c at baseline and at 6, 12, 18 and 24 months on 360 mg oral Verapamil once daily."}
• {"endpoint_text":"-Changes over time in insulin requirements as the total daily insulin dose (seven days average) in units per kg body weight (BW) in adults diagnosed with T1D receiving 360 mg oral Verapamil SR once daily, assessed at baseline (V-1) and 6-, 12- 18- and 24 months of therapy (V5 to V8)","definition_or_measurement_approach":"Total daily insulin dose averaged over seven days, normalized to units/kg body weight, measured at baseline and at 6, 12, 18 and 24 months."}
• {"endpoint_text":"-The number of treatment emergent severe hypoglycaemic episodes. Severe hypoglycaemia denotes severe cognitive impairment requiring external assistance for recovery according to the American Diabetes Association (ADA)","definition_or_measurement_approach":"Count of treatment-emergent severe hypoglycaemic episodes defined per ADA as events with severe cognitive impairment requiring external assistance."}
• {"endpoint_text":"-The number of treatment emergent episodes of diabetic ketoacidosis (DKA).","definition_or_measurement_approach":"Count of treatment-emergent diabetic ketoacidosis episodes occurring during the study."}
• {"endpoint_text":"-Adverse events, vital signs variation, ECG, laboratory safety parameters, measured at baseline (V-1) and 6-, 12- 18- and 24 of therapy (V5 to V8)","definition_or_measurement_approach":"Safety assessments including adverse events, vital signs, ECG and laboratory safety tests conducted at baseline and at 6, 12, 18 and 24 months."}

Austria

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

18-11-2024

Processing Time Days

39

Number Of Sites

1

Number Of Participants

2

Belgium

Earliest CTIS Part Ii Submission Date

24-10-2024

Latest Decision Or Authorization Date

11-11-2024

Processing Time Days

18

Number Of Sites

1

Number Of Participants

2

France

Earliest CTIS Part Ii Submission Date

24-10-2024

Latest Decision Or Authorization Date

13-11-2024

Processing Time Days

20

Number Of Sites

1

Number Of Participants

7

Germany

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

15-11-2024

Processing Time Days

39

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

14-11-2024

Processing Time Days

38

Number Of Sites

2

Number Of Participants

7

Primary sponsor

Full Name

Medical University Of Graz

Organisation Type

Educational Institution

Country Of Registered Address

Austria