Question 14.3

Discussion: The protocol assumes that effects of a dose will be apparent within a week. This will allow dose titration to occur on a weekly basis and allow the data during week 4 to validly reflect the full effects of the dose for those who are increased to the maximum dose over the four preceding weeks. This assumption is supported by the known pharmacokinetics of modafinil and clinical experience. If there was some doubt about the time required for a maximal effect to occur after dosing is initiated or the dose is increased, it would be best to begin the study with an open-label pilot phase, in which some idea of the timing of these effects could be developed.

The protocol indicates that the study will be conducted with just three visits (just two after screening). This is clearly an effort to reduce patient burden in recognition of the likelihood that a combination of fatigue and advanced illness will temper the enthusiasm of patients for multiple study visits. A visit at the end of week two ensures that some outcome data will be available from those patients who drop-out of the study during the last two weeks. Knowing the pharmacology of modafinil, are the procedures described adequate to ensure safety?

	Yes
	No