Food and Insulin Effect on QT/QTC Interval of ECG

Launched by RICHMOND PHARMACOLOGY LIMITED · Jul 13, 2012

Keywords

ClinConnect Summary

This study was initially performed in 24 healthy Caucasian and Japanese volunteers with an option to increase the sample size to up to 54 volunteers. The decision to increase the sample size to 32 was based on the standard deviation of the ECG intervals observed in the first 24 volunteers. This analysis was performed by an independent statistician under blinded conditions.

Each volunteer participated in 2 periods. Each period consisted of 1 baseline day (D-1) followed by 3 study days (D1 - D3) when the various food effect and drug treatments or placebo were administered. All volunteers rec...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Healthy male or female, 20 - 45 years old
• • 2. Signed ICF
• • 3. 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
• • 4. 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
• • 5. No clinical findings on the physical examination
• • 6. Body mass index (BMI) = 18 - 25 kg/m2, body weight at least 48 kg.
• • 7. Systolic blood pressure 90-145 mmHg, diastolic blood pressure 40-90 mmHg, and heart rate 40-90 bpm
• • 8. Triplicate 12 lead ECG without clinically relevant abnormalities
• • 9. 24 hour 12 lead Holter ECG without clinically relevant abnormalities
• • 10. Haematology, biochemistry and urinalysis within the normal range
• • 11. Must agree to use acceptable methods of contraception
• Exclusion Criteria:
• • 1. 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
• • 2. History of clinically significant syncope.
• • 3. Family history of sudden death.
• • 4. Family history of premature cardiovascular death.
• • 5. Family history of congenital long QT syndrome or Brugada's syndrome.
• • 6. History of arrhythmias and ischemic heart disease
• • 7. Conditions predisposing to electrolyte imbalances (e.g. altered nutritional states, chronic vomiting, anorexia nervosa, bulimia nervosa).
• • 8. Abnormal ECG in the standard 12-lead ECG and 24-hour 12 lead Holter ECG
• 9. 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 \< 350 msec or family history of long QT syndrome.
• • 10. Abnormal blood glucose result (blood glucose \>7.8mmol/l)
• • 11. Significant family history of diabetes mellitus.
• • 12. Significantly elevated fasting blood glucose level
• • 13. Signs and/or symptoms of acute illness in the four-week period prior to screening.
• • 14. Veins unsuitable for intravenous puncture or cannulation on either arm
• • 15. Known hypersensitivity to any medicines administered in the trial.
• • 16. Treatment with any prescribed medication during the 2 weeks prior to first baseline day.
• • 17. Treatment with any over-the-counter (OTC) medications during the 2 weeks prior to first baseline day.
• • 18. Treatment with vitamins and/or minerals within 48 hours prior to the first baseline day.
• • 19. 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.
• • 20. Positive urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates and methadone) or the alcohol breath test
• • 21. 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)
• • 22. Excessive caffeine consumption (≥800 mg per day)
• • 23. Smoking within 3 months prior to screening
• • 24. Loss of 250 mL or more blood within 3 months prior to screening.
• • 25. Positive results from the hepatitis serology, except for vaccinated subjects.
• • 26. Positive results from the HIV serology.
• • 27. Any circumstances or conditions, which may affect full participation in the study or compliance with the protocol.
• • 28. Legal incapacity or limited legal capacity.