TABLE 4

Correlation of secondary phenotyping metrics to the primary metric AUC_0–t of the parent substance

CYP	Secondary Metric	Silexan Treatment		Placebo Treatment
CYP	Secondary Metric	n	r ^d	n	r ^d
1A2	Molar paraxanthine / caffeine plasma concentration ratio 6 h post-dose^a	16	0.531^*	16	0.698**
2C9	Tolbutamide plasma concentration 24 h post-dose	16	0.842**	16	0.928**
2C19	Molar omeprazole/5-OH-omepazole plasma concentration ratio 3 h post-dose	15^b	0.697**	16	0.539^*
2C19	Molar omeprazole/5-OH-omepazole AUC_0–t ratio	16	0.905**	16	0.771**
2D6	Molar dextromethorphan/dextrorphan plasma concentration ratio 3 h post-dose	15^c	0.971**	15^c	0.983**
3A4	Midazolam plasma concentration 6 h post-dose	16	0.933**	16	0.855**

↵^a For calculation of this correlation, the inverse value (i.e., caffeine/paraxanthine ratio) was used.
↵^b Concentration in one subject in the silexan period was below LLOQ.
↵^c One subject excluded because identified as genetically poor metabolizer.
↵^d Pearson’s correlation coefficient.
↵*P = 0.05; **P = 0.01.