Effect of Hyperglycaemia and Moxifloxacin on QTc Interval in T2DM

NCT07014735 | Recruiting

• 1 other identifier: C20032
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Type 2; Hyperglycaemia (Diabetic); QT Interval, Variation in; Torsades de Pointes

Outcome Measures

Primary Outcomes (6)

• Clinically significant ECG morphology and interval changes from baseline

  ECG Analysis Mean QT/QTc values will be calculated for each time point (triplicate ECG) for subsequent analyses. Telemetry data gathered during the study may be used in the optional exploratory analysis of drug related QT/QTc interval changes. The primary baseline corrections will be calculated using averaged QTc pre-dose baseline values (three pre-dose time points). This single value will be used to calculate ΔQTc. A supplementary analysis to calculate ΔΔQTc may be performed using pooled placebo data. The effect on QTc will be calculated using concentration-effect analysis based on the placebo-corrected change from average baseline.

  Specified timepoints for 4 days and at follow up visit on Day10-D17

• Cardiac intervals/subintervals calculated using concentration-effect analysis on Days 1, 2, and 3.

  The primary baseline corrections will be calculated using averaged QTc pre-dose baseline values (three pre-dose time points). This single value will be used to calculate ΔQTc. A supplementary analysis to calculate ΔΔQTc may be performed using pooled placebo data. The effect on QTc will be calculated using concentration-effect analysis based on the placebo-corrected change from average baseline.

  Specified timepoints for 3 days

• The paired PK of blood glucose and moxifloxacin (Cmax)

  PK parameter: Maximum observed plasma concentration (Cmax) * Glucose * Day 1: Cmax * Day 2: Cmax * Day 3: Cmax * Day 4: Cmax * Moxifloxacin * Day 3: Cmax * Day 4: Cmax

  4 Days

• The paired PK of blood glucose and moxifloxacin (Tmax)

  PK parameter: time to reach maximum plasma concentration (Tmax) * Glucose * Day 1: Tmax * Day 2: Tmax * Day 3: Tmax * Day 4: Tmax * Moxifloxacin * Day 3: Tmax * Day 4: Tmax

  4 days

• The paired PK of blood glucose and moxifloxacin (AUC)

  PK parameter: Area under the plasma concentration-time curve (AUC). * Glucose * Day 1: AUC * Day 2: AUC * Day 3: AUC * Day 4: AUC * Moxifloxacin * Day 3: AUC * Day 4: AUC

  4 days

• Cardiac interval/subinterval parameters

  Cardiac interval/subinterval parameters (QTcF, JTpc, TpTe) prior to glucose administration compared to post-administration

  4 days

Secondary Outcomes (3)

• Comparison of the PK of blood glucose and moxifloxacin with cardiac interval/subinterval parameters and ECG morphology between sexes on Days 1, 2, 3 and 4

  Specified time points over 4 days

• • Concentration effect analysis between male and female volunteers on Days 1, 2, 3 and 4

  specified timepoints over 4 days

• The incidence of treatment-emergent adverse events (TEAEs)

  From screening to follow up approximately 75 days

Other Outcomes (1)

• To gain a comprehensive understanding of the molecular factors driving differences between male and female participants, by analysing a set of relevant biomarkers: insulin, C-peptide and glucagon.

  3 days

Study Arms (2)

glucose (controlled hyperglycaemia) and moxifloxacin placebo

PLACEBO COMPARATOR

Participants will receive glucose (controlled hyperglycaemia) and moxifloxacin placebo on Day 1. On Days 1 and 3 glucose will be administered intravenously and/or orally with the aim of gradually raising glucose concentration to 25-28 mmol/L over the space of an hour. The 25-28 mmol/L glucose level will be maintained for 1 hour. Intravenous glucose rate will be titrated up and down during the first hour as guided by glucose readings on CGMS/VBG. Glucose will be continuously monitored to guarantee concentration levels are maintained stable. At the 2-hour timepoint (H2), intravenous glucose will be terminated, and blood glucose level will be allowed to start reducing.

Drug: glucose

intravenous glucose in combination with intravenous moxifloxacin

EXPERIMENTAL

intravenous glucose in combination with intravenous moxifloxacin (300 mg infused over 45 minutes) on Day 3

Drug: glucose; Drug: moxifloxacin

Interventions

glucose DRUG

Participants will receive treatments with glucose or matching placebo (please see study design section).

glucose (controlled hyperglycaemia) and moxifloxacin placebo; intravenous glucose in combination with intravenous moxifloxacin

moxifloxacin DRUG

Participants will receive moxifloxacin or matching placebo (please see study design section).

intravenous glucose in combination with intravenous moxifloxacin

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female patients with stable T2DM. Diagnosis of T2DM confirmed by:
• i. Established diagnosis of T2DM documented on medical records and HbA1c at screening ≥ 48 mmol/mol (6.5%) and ≤ 80 mmol/mol (9.5%). Subjects with HbA1c levels \> 80 mmol/mol but ≤ 90 mmol/mol will be considered eligible, subject to approval by an endocrinologist. AND ii. Evidence of high insulin resistance as defined by a HOMA2-IR score within the top quintile of the locally defined cohort, \>0.55 (see Appendix 2).
• 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:
• a. Diet and exercise alone, b. Anti-glycaemic monotherapy on metformin, DPP-4i, pioglitazone, an SU or an SGLT-2i.
• 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
• 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:
• Combined i.e. (oestrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: \*\*
• Oral
• Intravaginal
• Transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation\*\*

You may not qualify if:

• 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).
• History of clinically significant syncope.
• Family history of sudden cardiac death.
• Clinically significant history or family history of congenital long QT syndrome (e.g., Romano-Ward syndrome, Jervell and Lange-Nielson syndrome) or Brugada syndrome.
• History of clinically significant arrhythmias (especially ventricular arrhythmias, atrial fibrillation (AF), recent conversion from AF), or bundle branch block.
• History of confirmed ischemic heart disease or current angina (including confirmed previous myocardial infarction, previous PCI, or coronary bypass).
• Conditions predisposing the volunteer to electrolyte imbalances other than T2DM (e.g., altered nutritional states, chronic vomiting, anorexia nervosa, bulimia nervosa, and other endocrine disorders including Cushing's' Addison's', or untreated hypo or hyperthyroidism).
• ECG abnormalities in the standard 12-lead ECG (at screening, Day -1 or pre-dose of Day 1) and 24-hour 12-lead Holter ECG or an equivalent assessment and/or submaximal exercise test (at screening) which in the opinion of the Investigator will interfere with the ECG analysis.
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This includes participants with any of the following (at screening,
• Day-1, or pre-dose on Day 1):

Sponsors & Collaborators

• Richmond Pharmacology Limited: lead
• Richmond Research Institute: collaborator

Study Sites (1)

Richmond Pharmacology Ltd.

London, SE1 1YR, United Kingdom

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hyperglycemia; Torsades de Pointes

Interventions

Glucose; Moxifloxacin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Tachycardia, Ventricular; Tachycardia; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Emma Akuffo

CONTACT

+442070425800; e.akuffo@richmondpharmacology.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The participant will be blinded to the administered medicinal products, but the clinical team will not.

Study Record Dates

• First Submitted: April 18, 2023
• First Posted: June 11, 2025
• Study Start: April 13, 2023
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

GB (1)