Type 2 diabetes mellitus MedDRA version: 20.0 Level: PT Classification code 10012601 Term: Diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: 18F-canagliflozin
Pharmaceutical Form: Infusion
INN or Proposed INN: Canagliflozin
CAS Number: 842133-18-0
Other descriptive name: CANAGLIFLOZIN
Concentration unit: µg microgram(s)
Conce
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Type 2 diabetes Age = 40 years =65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: • Pregnant women and women of child-bearing potential who are not using reliable contraception • eGFR < 30 mL/min/1.73 m2 • Subjects on diuretics are allowed to participate but the dose should be stable for at least 4 weeks prior to screening • Subjects already on a SGLT2 inhibitor are allowed to participate, but the drug should be interrupted 1 week prior to the first study day till the end of the second study day • Subjects using a sulphonylurea. • Established peripheral arterial disease • Cardiovascular disease: myocardial infarction, angina pectoris, percutanous transluminal coronary angioplasty, coronary artery bypass grafting, stroke, heart failure (NYHA I-IV) < 3 months before inclusion • History of hypersensitivity to canagliflozin or another SGLT2 inhibitor • Active malignancy • Donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing • History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening. • Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications • Severe claustrophobia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We hypothesize that the underlying mechanisms of the varying response to a drug in multiple parameters within an individual can be attributed to variability in the causal path between drug administration, drug tissue distribution, and tissue receptor interaction. In this clinical feasibility study we will assess 18F-canagliflozin pharmacokinetic characteristics and determine specific receptor binding, receptor occupancy and optimal scanning time in subjects with type 2 diabetes. The main objectives are: • To assess canagliflozin target (i.e. receptor) specific binding in vivo • To assess receptor occupancy of canagliflozin in vivo • To determine optimal scanning time in vivo ;Secondary Objective: To explore the relationship between canagliflozin disposition and changes in the following parameters: (estimated) Glomerular Filtration Rate, plasma glucose and urine glucose excretion;Primary end point(s): The main study parameters are dynamic PET data and images and radiation count measurement, and plasma concentrations of 18F canagliflozin and its metabolites. ;Timepoint(s) of evaluation of this end point: Per subjects 2 90 minutes dynamic PET scans will be performed, starting at the moment of 18F canagliflozin injection. Radiation activity and plasma concentrations of 18F canagliflozin will be measured during the PET scans. Plasma concentrations of 'cold' canagliflozin will be measured at time points pre-dose, 15, 25, 40, 60, 100, 150, 180, 210, 270 minutes and 24 h after oral dosing of canagliflozin | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary study parameters are plasma and urine glucose levels and (e)GFR.;Timepoint(s) of evaluation of this end point: Patients are asked to collect one urine void at the day of screening and to collect 2 times 24h urine at both study days (ie days at wich the PET scans will be performed). At screening and during both study days a fastend glucose will be measured and during the second PET scan point of care glucose measurements will be taken. | — |
Countries
Netherlands
Contacts
Public ContactH.J. Lambers Heerspink
University Medical Center Groningen
Outcome results
None listed