Efficacy and safety of phenylalanine-free amino acid-based formula(AA-PKU1) on Chinese infants with Phe-nylketonuria

Abstract

Objective To evaluate the efficacy and safety of phenylalanine-free amino acid-based formula(AA-PKU1) in the treatment of Chinese infants with phenylketonuria(PKU). Methods The prospective, open, self-controlled, multi-center trial was performed with a 32-week treatment period with recommended AA-PKU1 intake 20 g/(kg body weight·day). Each subject served as his/her own control and the values in treatment after 8 weeks and 32 weeks were compared to baseline.Total 39 PKU infants aged 0-4 months were enrolled in the study.The blood pheny-lalanine(PHE) level, developmental quotient(DQ), weight, height and head circumferences and nutritional biomarkers [total protein(TP), pre-albumin(Pre-Alb), albumin(Alb), total cholesterol(TC), total triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C)] were measured in baseline, after 8 weeks and 32 weeks, respectively.The routine blood & urine examination and the renal & hepatic function examinations were also conducted in baseline, after week 8 and week 32 with adverse events and adverse reactions observed during treatment. Results Three subjects dropped out, 36 subjects entered the per protocol set with the statistical analysis of efficacy conducted and 39 subjects entered the safety set with the statistical analysis of safety conducted during treatment after week 8.Five subjects dropped out, 34 subjects entered the per protocol set with the statistical analysis of efficacy conducted and 39 subjects entered the safety set with the statistical analysis of safety conducted during treatment after week 32.The mean blood PHE level in the treatment of week 8 and week 32 were 196.0 μmol/L and 191.1 μmol/L, respectively.Statistically significant differences were found between pre-treat PHE level(649.5 μmol/L) and post-treat PHE level(P<0.000 1). The PHE control rates in week 8 and week 32 were 88.89% and 88.24%, respectively(the PHE control level<360 μmol/L). The DQ scores in 5 function areas(adaptive behavior, gross motor, fine motor, language and personal-social behavior) in week 8 and week 32 were similar to baseline.The height, weight and head circumferences in week 8 and week 32 increased significantly compared with baseline(all P<0.000 1). The mean values of TP, Pre-Alb, Alb, TC, TG, LDL-C and HDL-C in week 8 and week 32 were close to baseline within the normal range.The drug-related adverse events(so-called: adverse drug reactions) occurred 14 times in 10 cases(8 cases of diarrhea, 1 case of vomiting and 1 case of diarrhea with vomiting) with mild to moderate severity.All these symptoms could either relieve themselves or disappear with symptomatic treatment. Conclusions AA-PKU1 can effectively maintain the ideal blood PHE level and normal intelligence development, and can fulfill normal growth needs and improve the nutritional condition for PKU infants.AA-PKU1 feeding was also safe and well tolerated for PKU infants. Key words: Phenylketonuria; Treatment; Infant; Clinical trial