Table 5.

Summary of outcomes associated with safety and tolerability achieved with FTY720 in clinical development

Level of evidence	Outcomes	FTY720 dosage	Study design and population	Reference
2	A total of 114 AEs reported by 36 subjects receiving FTY720 and placebo; 65 and 21% of the AEs were reported during the treatment and washout phases, respectively. About half of the AEs consisted of headache (31%), dizziness (9%), and nausea (7%) AE distribution was 16, 48, and 36% for FTY720 1.25 mg, FTY720 5 mg, and placebo groups, respectively	1.25 (n=20), or 5 mg (n=20), or placebo (n=20) once daily for 7 d	Randomized, double-blind, placebo-controlled, multiple-dose study in 60 healthy volunteers (age range 18–44 y)	Kovarik et al. 2004a
2	FTY720 preserved supine heart rate circadian rhythm. The heart rate vs time curve was shifted downwards by 10% over the first day postdose, recovering to prestudy values after 3–5 d postdose. All changes were asymptomatic and unaffected by the fasting or fed states	1 mg under fasting conditions or with a high-fat meal	Randomized, two-period, crossover study in 14 healthy male volunteers (age range 20–39 y)	Kovarik et al. 2004b
2	No serious AEs seen in the study. AEs occurred in 91% of FTY720-treated subjects vs 75% of placebo-treated subjects. Of the 28 AEs reported the most common were transient asymptomatic reduction in heart rate (n=10) and headache	0.25 (n=6), 0.5 (n=6), 0.75 (n=3), 1 (n=3), 2 (n=3), or 3.5 mg (n=3), or placebo (n=8)	Randomized, double-blind, placebo-controlled, two-center, single-dose study in 20 stable renal transplant patients (mean age 43.2 y)	Budde et al. 2002
2a	AEs were more frequently reported in the 5 mg group and the most frequent events (>15% of patients) were mild headaches and nasopharyngitis Treatment was well tolerated with 255 (91%) patients completing the study and 89% elected to continue to the extension phase	1.25 (n=94) and 5 mg (n=94) vs placebo (n=93)	Randomized, multicenter, double-blind, placebo-controlled 281 patients with active relapsing multiple sclerosis	Kappos et al. 2005
3	15 AEs reported in 9 subjects; 12 AEs in 7 hepatic-impaired subjects vs 3 AEs in 2 control subjects. 6 AEs were suspected to be related to FTY720: somnolence (n=2), dizziness, (n=2), dry mouth, and nausea The effect on supine heart rate was similar across all groups with a mean decrease of 13% from the predose rate occurring 2–4 h postdose and recovering within 1–2 d	1 mg	Open-label, single-dose, case-controlled study in 16 subjects with mild (n=8) or moderate (n=8) hepatic impairment and 16 matched controls	Kovarik et al. 2005

^aAbstract.

AE, adverse event; d, day; h, hour; y, year.