None listed
Conditions
Brief summary
Penthrox® (methoxyflurane) is an analgesic/device combination product, which is currently registered and marketed in Australia. Methoxyflurane belongs to the fluorinated hydrocarbon group of volatile anaesthetics. It is inhaled as a vapour at low (sub-anaesthetic) concentrations to provide analgesia in stable, conscious patients. hERG studies have indicated a potential for QT prolongation, a known property of this pharmacological class. However, clinical history has provided no indication that methoxyflurane may cause ventricular tachyarrhythmia or Torsades de Pointes (TdP) under conditions of use in analgesia. This study is specifically design to assess drug effects on the QT interval.
Interventions
This will be a single-centre, double-blind, double–dummy, randomised, placebo- and positive-controlled, 3 way crossover, thorough QT/QTc (TQT) study in healthy male and female subjects.
The effects of methoxyflurane at a supratherapeutic dose will be compared with matching placebo. A dose of 400 mg moxifloxacin will be included as a positive control for the effect on cardiac repolarisation.
Each active treatment (methoxyflurane and moxifloxacin) will have a placebo. There will be three treatm
This will be a single-centre, double-blind, double–dummy, randomised, placebo- and positive-controlled, 3 way crossover, thorough QT/QTc (TQT) study in healthy male and female subjects. The effects of methoxyflurane at a supratherapeutic dose will be compared with matching placebo. A dose of 400 mg moxifloxacin will be included as a positive control for the effect on cardiac repolarisation. Each active treatment (methoxyflurane and moxifloxacin) will have a placebo. There will be three treatment groups, defined as follows: A. single oral dose of moxifloxacin placebo + single inhaled dose of methoxyflurane (supratherapeutic dose) B. single oral dose of moxifloxacin (400 mg) + single inhaled dose of methoxyflurane placebo C. single oral dose of moxifloxacin placebo + single inhaled dose of methoxyflurane placebo. There is a washout period of 1 week (7days) between treatment periods. Twelve (12) mL of methoxyflurane is added to the inhaler. The single dose of methoxyflurane (and methoxyflurane placebo) consists of 12 consecutive breaths, with finger on diluter hole. Once the participants have been administered a treatment, they will be observed for 24 hours.
Sponsors
Medical Developments International
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy male and female subjects, aged 18 to 45 years inclusive, body mass index (BMI) >=18 and <=29 kg/m2, weight >=50 kg, with satisfactory medical history and current conditions, as defined.
Exclusion criteria
- Known cardiovascular disorders - ECG abnormalities that may reflect underlying heart disease and which may interfere with the accurate assessment of the QT interval - Known clinically significant arrhythmias or rhythm disturbances - A history of, or risk factors for Torsades de Pointes - A supine heart rate at screening outside 45-90 bpm - Consumption of any medication especially those with a known QT prolongation effect, within 30 days before the first dose of study drug, except occasional paracetamol use (up to 1 g/day). - Existence of any condition that could possibly interfere with drug absorption - Significant renal insufficiency, as indicated by an estimated creatinine clearance using the Cockcroft-Gault formula of <75 mL/min (males or females), at screening - Personal or family history of hypersensitivity to fluorinated anaesthetics
Outcome results
None listed