Regulatory Decision Summary for Foquest

Foquest is an extended release methylphenidate treatment.

Foquest generates a biphasic methylphenidate blood concentration profile with drug peak levels lower than those observed with IR formulations of methylphenidate. The second concentration peak with Foquest is observed 12.5 hours post-dose (range 11 to 16 hours). No significant food effect is observed, and the pharmacokinetics of methylphenidate are not altered when Foquest capsules are administered intact or as the contents sprinkled on apple sauce, yogurt or ice cream.

In the pivotal study 063-010, the primary endpoint was met as Foquest-treated subjects had a Clinician-rated ADHD-5-RS total score higher at Visit 6 compared to subjects who received placebo, for all doses of Foquest combined (p = 0.0026). The secondary endpoints included assessment of the individual doses. The efficacy of the 45 mg (p = 0.0013) and 100 mg (p = 0.0002) dose groups was statistically significant from placebo, whereas the 25 mg and 70 mg doses did not yield significant results on any of the parameters.

While the highest dose strength of Foquest (100 mg) is higher than any currently approved methylphenidate product in Canada, the pharmacokinetic data show that Foquest has a lower absorption rate compared to other formulations of methylphenidate. Indeed, based on dose normalised results, the maximum concentration (C_max) and extent (AUC_0-30h) of absorption were lower (by 70% and 20%, respectively) for Foquest when compared to an immediate-release formulation of methylphenidate tablets administered three times per day (TID). Foquests pharmacokinetic profile indicates that the total drug exposure and concentration peaks after a single 100 mg dose would not be higher than that obtained following a single dose of 80 mg of Biphentin, another approved biphasic methylphenidate formulation.

In the clinical trials, there were no significant differences in the severity or quantity of adverse events with Foquest compared to previously marketed methylphenidate products. The main concern with this new formulation was the potential impact it could have on sleep due to the higher blood levels of methylphenidate into the evening.

The ADHD patient population is known to have problems with sleep, and methylphenidate is also known to affect sleep quality. Because the blood level of Foquest peaks late in the day, the following precautionary wording has been added to the Dosage and Administration section of the PM: The effect of Foquest might last late into the evening, take as soon as possible in the morning to avoid any potential effect on your sleep.

Foquest was shown to be efficacious and had a similar safety profile to other marketed methylphenidate products. In light of this and the fact that a longer duration methylphenidate formulation may benefit some patient populations, the overall benefit-harm-uncertainty for Foquest in adult ADHD patients is considered favourable.