A central nervous system compound may require dose titration in order for the dose to be tolerated and to achieve a suprathereapeutic dose. Titration will require multiple doses over multiple days and in some cases, depending on the compound, may require more than 28 days to achieve the supratherapeutic dose. Even with careful dose titration, it still may not be possible for all participants to tolerate the targeted supratherapeutic dose.

Based on Cetero’s experience, one should consider scheduling Holter monitoring days over the course of the titration after designated doses have been achieved. These Holter monitoring days will provide data at doses exceeding the clinical dose, in case participants are not able to continue to the supratherapeutic dose.