Food and Insulin Effect on QT/QTC Interval of ECG

Inclusion Criteria

• Healthy male or female, 20 - 45 years old
• Signed ICF
• Japanese - a descendant of four Japanese grandparents, carrying a Japanese passport and has not been outside Japan for more than 5 years prior to screening
• The Caucasian - light to brown skin pigmentation; straight to wavy or curly hair; indigenous to Europe, northern Africa, western Asia, and India. The study may also include Caucasians from North America, Australia and South Africa
• No clinical findings on the physical examination
• Body mass index (BMI) = 18 - 25 kg/m2, body weight at least 48 kg.
• Systolic blood pressure 90-145 mmHg, diastolic blood pressure 40-90 mmHg, and heart rate 40-90 bpm
• Triplicate 12 lead ECG without clinically relevant abnormalities
• 24 hour 12 lead Holter ECG without clinically relevant abnormalities
• Haematology, biochemistry and urinalysis within the normal range
• Must agree to use acceptable methods of contraception

Exclusion Criteria

• 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
• History of clinically significant syncope.
• Family history of sudden death.
• Family history of premature cardiovascular death.
• Family history of congenital long QT syndrome or Brugada's syndrome.
• History of arrhythmias and ischemic heart disease
• Conditions predisposing to electrolyte imbalances (e.g. altered nutritional states, chronic vomiting, anorexia nervosa, bulimia nervosa).
• Abnormal ECG in the standard 12-lead ECG and 24-hour 12 lead Holter ECG
• Abnormal rhythm, conduction or morphology of resting ECG, such as:
• Sinus node dysfunction.
• Clinically significant PR (PQ) interval prolongation.
• Intermittent second or third degree AV block.
• Incomplete or complete bundle branch block.
• Abnormal T wave morphology.
• Prolonged QTcB >450 msec or shortened QTcB 7.8mmol/l)
• Significant family history of diabetes mellitus.
• Significantly elevated fasting blood glucose level
• Signs and/or symptoms of acute illness in the four-week period prior to screening.
• Veins unsuitable for intravenous puncture or cannulation on either arm
• Known hypersensitivity to any medicines administered in the trial.
• Treatment with any prescribed medication during the 2 weeks prior to first baseline day.
• Treatment with any over-the-counter (OTC) medications during the 2 weeks prior to first baseline day.
• Treatment with vitamins and/or minerals within 48 hours prior to the first baseline day.
• Treatment with another investigational drug within 4 weeks prior to dosing or having participated in more than 3 investigational drug studies within a year prior to dosing.
• Positive urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates and methadone) or the alcohol breath test
• History or clinical evidence of alcoholism (regular weekly alcohol intake of more than 14 units if female and 21 units if male) or drug abuse (compulsive, repetitive and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms)
• Excessive caffeine consumption (≥800 mg per day)
• Smoking within 3 months prior to screening
• Loss of 250 mL or more blood within 3 months prior to screening.
• Positive results from the hepatitis serology, except for vaccinated subjects.
• Positive results from the HIV serology.
• Any circumstances or conditions, which may affect full participation in the study or compliance with the protocol.
• Legal incapacity or limited legal capacity.