OPEN, NON-COMPARATIVE PHASE III CLINICAL STUDY TO EVALUATE THE EFFICACY AND SAFETY OF SAPROPTERIN IN PATIENTS WITH PHENYLKETONURIA AND HYPERPHENYLALANINEMIA

Cover Page
  • Authors: Bushueva T.V.1, Kuzenkova L.M.2, Borovik T.E.2, Nazarenko L.P.3, Seitova G.N.3, Filimonova M.N.3, Pichkur N.A.4, Samonenko N.V.4, Shkurko T.A.4, Akhmadeeva E.N.5, Mardanova A.K.6, Garifullina E.R.6, Kovtun O.P.7, Bazhenova Y.L.7, Alimova I.L.8, Kostyakova E.A.8, Minaicheva L.I.3, Salyukova O.A.3, Sivokha V.M.3, Rosenson O.L.9
  • Affiliations:
    1. Scientific Center of Children Health, Moscow
    2. Scientific Center of Children Health, Moscow, Russian Federation
    3. Research Institute of Medical Genetics, Tomsk, Russian Federation
    4. National Children’s Hospital «Ohmatdyt», Kiev, Ukraine
    5. Bashkir State Medical University, Ufa, Republic of Bashkortostan, Russian Federation
    6. Republican Perinatal Centre, Ufa, Republic of Bashkortostan, Russian Federation
    7. Ural State Medical University, Ekaterinburg, Russian Federation
    8. Smolensk State Medical Academy, Russian Federation
    9. LLC «Merck», Moscow, Russian Federation
  • Issue: Vol 69, No 7-8 (2014)
  • Pages: 69-77
  • Section: PEDIATRICS: CURRENT ISSUES
  • URL: https://vestnikramn.spr-journal.ru/jour/article/view/409
  • DOI: https://doi.org/10.15690/vramn.v69i7-8.1111
  • Cite item

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. Aim: The present open, noncomparative 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. Patients and 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. Conclusion: The study results confirmed the efficacy and safety of sapropterin therapy in patients with PKU, which is consistent with international clinical trials data.


T. V. Bushueva

Scientific Center of Children Health, Moscow

Author for correspondence.
Email: bushueva@nczd.ru

Russian Federation

MD, senior research scientist of the Department of Healthy and Ill Child Nutrition of SCCH

 

L. M. Kuzenkova

Scientific Center of Children Health, Moscow, Russian Federation

Email: kuzenkova@nczd.ru

Russian Federation

доктор медицинских наук, профессор, заведующая отделением психоневрологии и психосоматической патологии Научного центра здоровья детей Адрес: 119991, Москва, Ломоносовский проспект, д. 2, стр. 1, тел.: +7 (499) 134-04-09

T. E. Borovik

Scientific Center of Children Health, Moscow, Russian Federation

Email: borovik@nczd.ru

Russian Federation

доктор медицинских наук, профессор, руководитель отделения питания здорового и больного ребенка Научного центра здоровья детей Адрес: 119991, Москва, Ломоносовский проспект, д. 2, стр. 1, тел.: +7 (499) 132-26-00

L. P. Nazarenko

Research Institute of Medical Genetics, Tomsk, Russian Federation

Email: Liudmila.nazarenko@medgenetics.ru

Russian Federation доктор медицинских наук, профессор, заместитель директора по научной и лечебной работе НИИМГ Адрес: 634050, Томск, Московский тракт, д. 3, тел.: +7 (3822) 53-56-81

G. N. Seitova

Research Institute of Medical Genetics, Tomsk, Russian Federation

Email: seitova-g@mail.ru

Russian Federation

кандидат медицинских наук, врач-генетик НИИМГ Адрес: 634050, Томск, Московский тракт, д. 3, тел.: +7 (3822) 53-56-81

M. N. Filimonova

Research Institute of Medical Genetics, Tomsk, Russian Federation

Email: margarita.filimonova@medgenetics.ru

Russian Federation

заведующая отделением наследственных болезней НИИМГ Адрес: 634050, Томск, Московский тракт, д. 3, тел.: +7 (3822) 53-56-81

N. A. Pichkur

National Children’s Hospital «Ohmatdyt», Kiev, Ukraine

Email: pichkurnat@mail.ru

Ukraine кандидат медицинских наук, заведующая Центром метаболических заболеваний НДСП «Охматдет» Минздрава Украины Адрес: 01135, Украина, Киев, ул. Чорновола, д. 28/1, тел.: +38 (044) 236-01-19

N. V. Samonenko

National Children’s Hospital «Ohmatdyt», Kiev, Ukraine

Email: natalisam@gmail.com

Ukraine врач-педиатр Центра метаболических заболеваний НДСП «Охматдет» Минздрава Украины Адрес: 01135, Украина, Киев, ул. Чорновола, д. 28/1, тел.: +38 (044) 236-01-19

T. A. Shkurko

National Children’s Hospital «Ohmatdyt», Kiev, Ukraine

Email: tanusha-doc@yandex.ru

Ukraine врач-педиатр Центра метаболических заболеваний НДСП «Охматдет» Минздрава Украины Адрес: 01135, Украина, Киев, ул. Чорновола, д. 28/1, тел.: +38 (044) 236-01-19

E. N. Akhmadeeva

Bashkir State Medical University, Ufa, Republic of Bashkortostan, Russian Federation

Email: pediatr@ufanet.ru

Russian Federation

доктор медицинских наук, профессор, заведующая кафедрой госпитальной педиатрии БГМУ Адрес: 450000, Россия, Республика Башкортостан, Уфа, ул. Ленина, д. 3, тел.: +7 (3472) 72-41-73

A. K. Mardanova

Republican Perinatal Centre, Ufa, Republic of Bashkortostan, Russian Federation

Email: mgkufa@rambler.ru

Russian Federation

кандидат медицинских наук, заведующая медико-генетической консультацией Республиканского перинатального центра г. Уфы Адрес: 450076, Россия, Республика Башкортостан, Уфа, ул. Чернышевского, д. 41, тел.: +7 (3472) 72-32-30

E. R. Garifullina

Republican Perinatal Centre, Ufa, Republic of Bashkortostan, Russian Federation

Email: bogdalova_emy7@mail.ru

Russian Federation

врач-генетик Республиканского перинатального центра г. Уфы Адрес: 450076, Россия, Республика Башкортостан, Уфа, ул. Гафури, д. 74, тел.: +7 (3472) 72-32-30

O. P. Kovtun

Ural State Medical University, Ekaterinburg, Russian Federation

Email: pediatr.fpk@bk.ru

Russian Federation доктор медицинских наук, профессор, заведующая кафедрой педиатрии и неонатологии ФПК и ПП, проректор по НИР УГМУ Адрес: 620028, Екатеринбург, ул. Репина, д. 3, тел.: +7 (3432) 14-86-62

Yu. L. Bazhenova

Ural State Medical University, Ekaterinburg, Russian Federation

Email: pediatr.fpk@bk.ru

Russian Federation

ассистент кафедры педиатрии и неонатологии ФПК и ПП, проректор по НИР УГМУ Адрес: 620028, Екатеринбург, ул. Репина, д. 3, тел.: +7 (3432) 14-86-62

I. L. Alimova

Smolensk State Medical Academy, Russian Federation

Email: iri-alimova@yandex.ru

Russian Federation доктор медицинских наук, профессор, заведующая кафедрой госпитальной педиатрии с курсом неонатологии ФПК и ППС СГМА Адрес: 214019, Смоленск, ул. Крупской, д. 28, тел.: +7 (4812) 55-54-94

E. A. Kostyakova

Smolensk State Medical Academy, Russian Federation

Email: katyalimova@yandex.ru

Russian Federation

аспирант кафедры госпитальной педиатрии с курсом неонатологии ФПК и ППС СГМА Адрес: 214019, Смоленск, ул. Крупской, д. 28, тел.: +7 (4812) 55-54-94

L. I. Minaicheva

Research Institute of Medical Genetics, Tomsk, Russian Federation

Email: larisa.minaycheva@medgenetics.ru

Russian Federation кандидат медицинских наук, врач-генетик НИИМГ Адрес: 634050, Томск, Московский тракт, д. 3, тел.: +7 (3822) 53-56-81

O. A. Salyukova

Research Institute of Medical Genetics, Tomsk, Russian Federation

Email: olga.salukova@mail.ru

Russian Federation кандидат медицинских наук, врач-генетик НИИМГ Адрес: 634050, Томск, Московский тракт, д. 3, тел.: +7 (3822) 53-56-81

V. M. Sivokha

Research Institute of Medical Genetics, Tomsk, Russian Federation

Email: verams23@sipmail.com

Russian Federation

врач-педиатр консультативно-поликлинического отделения НИИМГ Адрес: 634050, Томск, Московский тракт, д. 3, тел.: +7 (3822) 53-56-81

O. L. Rosenson

LLC «Merck», Moscow, Russian Federation

Email: oleg.rozenson@merckgroup.com

Russian Federation

кандидат медицинских наук, медицинский директор ООО «Мерк» Адрес: 125445, Москва, ул. Смольная, д. 24Д, тел.: +7 (495) 937-33-04

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