Healthy, male and female subjects between 18 and 55 years of age inclusive. (1)
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Body mass index of 19 to 29 kg/m2, with a body weight of at least 50kg. (2)
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No abnormality on clinical examination. A subject with a clinical abnormality may be included only if the Principal Investigator, in agreement with the Sponsor, considers that the abnormality will not introduce additional risk factors and will not interfere with the study procedures. (3)
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No abnormality revealed by the clinical laboratory parameters examination at the pre study medical examination. Subjects with laboratory values outside the reference range for this age group will only be included if the Principal Investigator considers that such findings will not introduce risk factors. (4)
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A normal 12-lead ECG at the pre-study screening. (5)
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Normal systolic (100-400mmHg) and diastolic (<90mmHg) blood pressure (Supine) at pre study screening and pre-dose Day 1. (6)
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Written informed consent prior to admission to the study. (7)
Any clinically relevant abnormality identified on the screening 12-lead ECG: QTcB interval >430 msec (male or >450 msec (female) (2)
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History or presence of clinically significant cardiovascular, neurological, psychiatric, haematological or renal abnormalities. (3)
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History of postural hypotension or faints. (4)
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Supine Systolic BP <100mmHg and diastolic BP < 60mmHg at screening. (5)
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Orthostatic decrease (supine to erect) in BP for systolic > 20mmHg and diastolic > 10mmHg at screening. (6)
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History or presence of gastrointestinal, hepatic or renal disease or any other condition known to (7)
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The subject has received prescribed medication within 14 days or over-the-counter (OTC) medicine within 7 days before the first dosing day (apart from medications that are described below in 6 and 7), which in the opinion of the Principal Investigator may interfere with the study procedures or compromise a subjects’ safety. Subjects who have taken OTC medication may still be entered into the study, if, in the opinion of the Principal/Co-investigator in agreement with the Sponsor, the medication received will not interfere with the study procedures or compromise subjects’ safety. (8)
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The subject has received prescribed medication within 14 days or over-the-counter (OTC) medicine within 7 days before the first dosing day (apart from medications that are described below in 6 and 7), which in the opinion of the Principal Investigator may interfere with the study procedures or compromise a subjects’ safety. Subjects who have taken OTC medication may still be entered into the study, if, in the opinion of the Principal/Co-investigator in agreement with the Sponsor, the medication received will not interfere with the study procedures or compromise subjects’ safety. (8)
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Women on cyclic HRT treatments during which the proportions of oestrogen and progesterone are not kept constant throughout their 28-day cycle. (9)
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Withdrawal, introduction, or change in dose of any drug known to substantially inhibit CY1A2 (e.g.ciprofoxcin, fluvoxamine, cimetidine, ethinylostradiol) or induce CYP1A2 (e.g. tobacco, omeprazole) within 7 days prior to first day of dosing. Subjects who are on stable doses (no change within 7 days of 1st dose) or any CYP1A2 inhibitors or inducers are permitted to participate, if, in the opinion of the Principal investigator and in agreement with the Sponsor, the medication received will not interfere with the study procedures or compromise subjects’ safety. (10)
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Pregnancy and/or breast feeding. (11)
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Females of child-bearing potential who are not practising a clinically accepted method of contraception such as surgical sterilisation, I.U.D.,diaphragm in conjunction with spermicidal foam and condom on the male partner, or systemic contraception (i.e., Norplant). Males subjects with female partners must also pratice a clinically accepted method of contraception. (12)
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Female subjects with positive urine/serum pregnancy test result at screening or prior to first dose. (13)
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Recent history (within the last 6 months), or suspicion, of drug dependence or a positive screening or pre-dose drugs of abuse screen. (14)
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Abuse of alcohol (defined as an average weekly intake of greater than 21 units or and average daily intake greater than 3 units for men; greater than 14 units per week or greater than 2 units per day for women. One unit is equivalent to half a pint of beer, one measure of spirits or one glass of wine) or a positive screening or pre-dose alcohol test. (15)
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Positive pre-study screening result for hepatitis B surface antigen, hepatitis C antibody or HIV - 1/2 antibodies. (16.)
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Participation in another clinical trial, blood donation less than 90 days before the present study. (17)
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Definite or suspected personal history or family history or adverse reactions or hypersensitivity to the study drug or to drugs with a similar chemical structure. (18)