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B -- VARIATIONS IN THE DRUG-INDUCED QT INTERVAL PROLONGATION DURING THE MENSTRUAL CYCLE SOL B21046-00-98 DUE 083198 POC Trudy Dartouzos, Contract Specialist, ph: 301/827-7165; fax: 301/827-7103 See Note #1. The Food and Drug Administration [FDA], intends to award a purchase order to Georgetown University to examine the influence of menstrual cycle on the response to a drug that prolongs cardiac repolarization [QT interval on the ECG]. Approximately 20 women shall be studied coinciding with the menstrual, follicular and luteal phases of the menstrual cycle. First visit shall be performed 24-48 hours after onset of the menses [menstrual phase]; second visit 24-48 hours after urinary test for ovulation; and third visit 7-9 days after ovulation [luteal phase]. Each menstrual cycle phase shall be confirmed later with the result of the serum estrogen and progresterone levels. Work shall be addresses to potential gender differences in the QT response to lthe drug ibutilide [20 males and 20 females to be studied]. The sample size has been calculated using the results of a previous pilot study and found a mean QTc prologation of 40 + [+ underlined] 13 msec [SD]. ECGs shall be recorded using a MacVu Marquette ECG system and stored on disk. The QT interval shall be analyzed using validated computer-operator interactive program and digitizing pad. For each ECG, the RR interval and QT interval shall be measured for the first three consecutive normal and technically acceptable [artifact free] beats and results averaged to provide the RR interval and the QT interval for tracing. The ECG tracings shall be placed on a digitizing pad [summagraphics] and taped in place. The QT duration will be measured for a cardiac cycle [PQRSTU] from 12 leads simultaneously using the earlist beginning of the QRS complex to the end of the longest T wave in any three of the leads. Data will be transmitted to a Windows-based computer for analysis and storage. The mean rate corrected QT, QTc shall be computed by the Bazett's formula for the three recorded beats. The data shall be summarized and stored in Excel spreadsheets. Written quotes are due 2:00 p.m., 8/31/98. Posted 08/11/98 (W-SN235584). (0223)

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