Effect of Hyperglycaemia and Moxifloxacin on QTc Interval in T2DM (NCT07014735) | Clinical Trial Compass
RecruitingNot Applicable
Effect of Hyperglycaemia and Moxifloxacin on QTc Interval in T2DM
United Kingdom24 participantsStarted 2023-04-13
Plain-language summary
Diabetes is a significant risk factor for sudden cardiac death, with the QTc interval on electrocardiograms (ECGs) often prolonged in diabetic patients due to factors such as hyperglycaemia and insulin resistance. Drugs like moxifloxacin can further exacerbate this effect, especially in those with diabetes. A previous trial on Type 1 diabetes suggested that hyperglycaemia and moxifloxacin have additive effects, prompting an investigation into whether similar effects occur in Type 2 diabetes (T2DM), particularly in individuals with high insulin resistance. This study aims to evaluate whether moxifloxacin-induced QT-prolongation is amplified by elevated blood glucose levels or insulin deficiency in T2DM patients, considering potential differences between sexes. Blood biomarkers will be analysed to understand the underlying molecular mechanisms. The trial will involve at least 24 male and female participants with insulin-resistant T2DM, aged 18 to 64 years, conducted at Richmond Pharmacology Ltd. Participants will receive treatments with glucose, moxifloxacin, and placebos while closely monitored for side effects during an inpatient stay, followed by outpatient appointments.
Who can participate
Age range18 Years – 64 Years
SexALL
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Inclusion criteria
✓. Male or female patients with stable T2DM. Diagnosis of T2DM confirmed by:
✓. 18-64 years (inclusive) of age (at the date of signing informed consent), with a body mass index of 18 to 35 kg/m², inclusive (at screening).
✓. Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluation (haematology, biochemistry, coagulation, and urinalysis) that is reasonably likely to interfere with the participant's ability to complete the study as assessed by the Investigator.
✓. Stable patients with insulin resistant type 2 diabetes treated with one of the following:
✓. Able to wash-out anti-glycaemic therapy for ten half-lives prior to dosing or at D-7, whichever is longer, and for the duration of the trial period up to the end of Day 4.
✓. Participants must agree to use the following contraceptive requirements for the applicable duration:
✓. Female participants of non-childbearing potential (WNCBP): Defined as either postmenopausal (evidence of menopause based on a combination of amenorrhea for at least one year and increased serum follicle-stimulating hormone (FSH) level \[\> 30 IU/L\]), or surgical sterilization (evidence of hysterectomy and/or bilateral oophorectomy). CONTRACEPTION REQUIRED: None
What they're measuring
1
Clinically significant ECG morphology and interval changes from baseline
Timeframe: Specified timepoints for 4 days and at follow up visit on Day10-D17
2
Cardiac intervals/subintervals calculated using concentration-effect analysis on Days 1, 2, and 3.
Timeframe: Specified timepoints for 3 days
3
The paired PK of blood glucose and moxifloxacin (Cmax)
Timeframe: 4 Days
4
The paired PK of blood glucose and moxifloxacin (Tmax)
Timeframe: 4 days
5
The paired PK of blood glucose and moxifloxacin (AUC)
✓. Female participants of childbearing potential (WOCBP) who anticipate being sexually active with a male during the trial (from one complete menstrual cycle prior to the first drug administration until three months after the last drug administration) \*: CONTRACEPTION REQUIRED: Highly effective contraception must start one complete menstrual cycle prior to the first day of dosing and continue until three months after drug administration. Highly effective contraception methods for WOCBP include:
Exclusion criteria
✕. History or clinical evidence of T2DM related secondary complications in particular autonomic neuropathy, cardiac rhythm disturbances, past medical history of syncope and potassium abnormalities.
✕. Currently prescribed or used in the last 12 months any form of insulin therapy, or any long half-life diabetic medication that would not wash-out within 7 days.
✕. History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the study drug (appendicectomy and herniotomy allowed).
✕. History or clinical evidence of significant microvascular disease including chronic kidney failure, macular degeneration or any other disease attributed to the microvascular system that in the Investigator's opinion may affect the outcome of the study.
✕. Recent hospitalisation due to hypoglycaemia or hyperglycaemia within 28 days before screening.
✕. History or clinical evidence of any disease with a specific contraindication to moxifloxacin (hypersensitivity, history of tendon disease related to quinolone treatment, and risk of QT prolongation conditions as below).