Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4 years: results from the SPARK open-label, multicentre, randomized phase IIIb trial

Table 5 Summary of safety data showing the proportion of patients reporting adverse events (AEs) (Safety population)

	Sapropterin + Phe-restricted diet (n = 27)		Phe-restricted diet alone (n = 27)
	Patients, n (%)	Events, n	Patients, n (%)	Events, n
Treatment-emergent AEs	27 (100)	282	27 (100)	278
AEs related to sapropterin	8 (29.6)	31	NA	NA
Infections and infestations related to sapropterin	3 (11.1)	3	NA	NA
Gastrointestinal disorders related to sapropterin	3 (11.1)	8	NA	NA
Amino acid concentrations decrease related to sapropterin	6 (22.2)	20	NA	NA
SAEs	3 (11.1)	5	1 (3.7)	2
Gastroenteritis	1 (3.7)	1	0 (0.0)	0
Rash	1 (3.7)	1	0 (0.0)	0
Overdose^a	1 (3.7)	2	0 (0.0)	0
Stomatitis	1 (3.7)	1	0 (0.0)	0
Bronchiolitis	0 (0.0)	0	1 (3.7)	1
Bronchopneumonia	0 (0.0)	0	1 (3.7)	1
AEs leading to discontinuation	0 (0.0)	0	0 (0.0)	0

NA not appropriate, SAE serious AE
^aOn the day of first administration of study treatment, the subject had a sapropterin overdose (severity: mild; 80 mg/day instead of 75 mg/day by mistake). At 26 days after the first administration of study treatment, the subject had another sapropterin overdose (severity: mild; 80 mg/day instead of 75 mg/day by mistake). Both events were reported in accordance with the protocol and were therefore categorized as medically important. The subject recovered without sequelae from both events. The administration of sapropterin plus Phe-restricted diet alone was continued without change after the first overdose and the dose was reduced after the second overdose
AE defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have a causal relationship with trial treatment; SAE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening; might have caused death if it had been more severe; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or was otherwise considered as medically important

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