 - Withdrawal, introduction, or change in dose of hormone replacement therapy andor any drug known to substantially inhibit cytochrome P 450 1A2 CYP1A2 e.g. ciprofloxacin, fluvoxamine, cimetidine, ethinyloestradiol or induce CYP1A2 e.g. tobacco, omeprazole within 7 days prior to enrolment. Subjects already on chronic therapy with any of these agents may be enrolled but doses must have remained stable from 7 days prior to enrolment through the end of the treatment period. 