Table 2.

Statistical comparison of primary oral contraceptive pharmacokinetic and pharmacodynamic endpoints following co-administration of Microgynon^® 30 (1 tablet/day comprising 30 μg ethinyl estradiol and 150 μg levonorgestrel) and fostamatinib (100 mg twice daily)

Analyte	Parameter (units)	Treatment	n	Geometric LS mean	Microgynon + fostamatinib/microgynon alone
					Ratio (%)	90 % CI
Ethinyl estradiol	AUCss (ng·h/mL)	Microgynon alone	27	828.1
		Microgynon + fostamatinib	27	1062	128.2	121.1–135.8
	C max,ss (ng/mL)	Microgynon alone	27	86.2
		Microgynon + fostamatinib	27	115.7	134.3	126.1–143.0
Levonorgestrel	AUCss (ng·h/mL)	Microgynon alone	27	75,970
		Microgynon + fostamatinib	27	79,830	105.1	97.5–113.2
	C max,ss (ng/mL)	Microgynon alone	27	6652
		Microgynon + fostamatinib	27	6439	96.8	90.4–103.6
Progesterone	AUCss (nmol·h/L)	Microgynon alone	27	66.5
		Microgynon + fostamatinib	27	69.4	104.3	96.4–112.9
	C max,ss (nmol/L)	Microgynon alone	27	4.9
		Microgynon + fostamatinib	27	4.9	99.8	90.4–110.1
Sex hormone-binding globulin	AUCss (nmol·h/L)	Microgynon alone	27	2020
		Microgynon + fostamatinib	27	2023	100.1	94.9–105.7
	C max,ss (nmol/L)	Microgynon alone	27	92.6
		Microgynon + fostamatinib	27	92.9	100.4	94.3–106.9
Follicle-stimulating hormone	AUCss (IU·h/L)	Microgynon alone	27	5.6
		Microgynon + fostamatinib	27	4.3	75.6	62.1–92.1
	C max,ss (IU/L)	Microgynon alone	27	0.3
		Microgynon + fostamatinib	27	0.2	76.0	56.2–102.7
Luteinizing hormone	AUCss (IU·h/L)	Microgynon alone	27	4.4
		Microgynon + fostamatinib	27	3.7	83.2	65.5–105.7
	C max,ss (IU/L)	Microgynon alone	27	0.3
		Microgynon + fostamatinib	27	0.2	75.6	51.3–111.6

Results were analyzed by employing a linear fixed-effects model with treatment and subject as fixed effects

AUC _ss area under the plasma concentration–time curve during the dosing interval at steady state, CI confidence interval, C _max,ss maximum plasma concentration at steady state, LS least-squares