title: [Open, non-comparative phase III clinical study to evaluate the efficacy and safety of sapropterin in patients with phenylketonuria and hyperphenylalaninemia].
abstract: BACKGROUND
  Phenylketonuria (PKU) is an autosomal recessive inherited disease associated with impaired metabolism of the amino acids phenylalanine (Phe) and tyrosine. The main criterion for diagnosis of PKU is high blood Phe level determined during neonatal screening. In case where PKU patient is responsive to tetrahydrobiopterin treatment, sapropterin restores the impaired activity of the enzyme phenylalanine hydroxylase, resulting in the stimulation of normal Phe metabolism and thereby enhancing patient tolerance to natural products.
  
  
  OBJECTIVE
  The present open, non-comparative clinical study was initiated to assess the degree and frequency of response after 8-day sapropterin administration and assess the safety of 6-week sapropterin treatment in patients with PKU and hyperphenylalaninemia.
  
  
  METHODS
  The study enrolled 90 patients with PKU. The criterion of response to 8-day sapropterin therapy was the reduction of Phe blood levels ≥ 30% compared with the baseline value.
  
  
  RESULTS
  Positive response to treatment was observed in 30 (33.3%) patients (95% CI 23.7-44.1). The mean percentage change in Phe blood levels after the 8-day response test period compared to Phe levels prior to dosing was 14.1 ± 28.4% in the overall subject population (95% CI 8.2-20.1) and 44.3 ± 15.1% in the subpopulation of patients with a positive response (95% CI 38.6-49.9). During the study, adverse events were reported in 24 (26.7%) patients in the overall population in 16 (53.3%) patients in the subpopulation who had a response.
  
  
  CONCLUSIONS
  The study results confirmed the efficacy and safety of sapropterin therapy in patients with PKU, which is consistent with international clinical trials data.
authors.forename: T V
authors.initials: TV
authors.lastname: Bushueva
authors.forename: L M
authors.initials: LM
authors.lastname: Kuzenkova
authors.forename: T É
authors.initials: TÉ
authors.lastname: Borovik
authors.forename: L P
authors.initials: LP
authors.lastname: Nazarenko
authors.forename: G N
authors.initials: GN
authors.lastname: Seitova
authors.forename: M N
authors.initials: MN
authors.lastname: Filimonova
authors.forename: N A
authors.initials: NA
authors.lastname: Pichkur
authors.forename: N V
authors.initials: NV
authors.lastname: Samonenko
authors.forename: T A
authors.initials: TA
authors.lastname: Shkurko
authors.forename: É N
authors.initials: ÉN
authors.lastname: Akhmadeeva
authors.forename: A K
authors.initials: AK
authors.lastname: Mardanova
authors.forename: É R
authors.initials: ÉR
authors.lastname: Garifullina
authors.forename: O P
authors.initials: OP
authors.lastname: Kovtun
authors.forename: Iu L
authors.initials: IuL
authors.lastname: Bazhenova
authors.forename: I L
authors.initials: IL
authors.lastname: Alimova
authors.forename: E A
authors.initials: EA
authors.lastname: Kostiakova
authors.forename: L I
authors.initials: LI
authors.lastname: Minaĭcheva
authors.forename: O A
authors.initials: OA
authors.lastname: Saliukova
authors.forename: V M
authors.initials: VM
authors.lastname: Sivokha
authors.forename: O L
authors.initials: OL
authors.lastname: Rozenson
mesh_terms: D000293:Adolescent; D001708:Biopterins / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D003067:Coenzymes / Q000008:administration & dosage / Q000009:adverse effects; D004093:Dihydropteridine Reductase / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods; D010649:Phenylalanine / Q000097:blood*; D010651:Phenylalanine Hydroxylase / Q000378:metabolism; D010661:Phenylketonurias / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D003067:Coenzymes; D001708:Biopterins; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; D004093:Dihydropteridine Reductase; C003402:sapropterin