Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study
Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study
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DOI：
10.1016/s0140-6736(07)61234-3
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发表时间：
2007-08-11
期刊：
影响因子：
168.9
通讯作者：
Dorenbaum, Alex
中科院分区：
文献类型：
--
作者：
Levy, Harvey L.;Milanowski, Andrzej;Dorenbaum, Alex
背景及早严格的苯丙酮尿症饮食管理是预防智力低下的唯一选择。我们的目的是测试四氢生物蝶呤(BH4)的合成形式腐普蝶呤降低苯丙氨酸血药浓度的疗效。方法89例苯丙酮尿症患者参加了一项III期多中心、随机、双盲、安慰剂对照试验。我们随机将42名患者分为两组，42名患者接受口服腐普蝶林(10 mg/kg)，47名患者接受安慰剂治疗，每天一次，持续6周。主要终点是6周后血液中苯丙氨酸浓度较基线的平均变化。分析建立在意向治疗的基础上。这项研究在ClinicalTrials.gov注册，编号NCT00104247。发现89名登记的患者中有88人至少接受了一剂研究药物，其中87人参加了第6周的访问。平均年龄20岁(SD 9.7)。基线时，接受腐胺喋呤治疗的患者血液中苯丙氨酸的平均浓度为843(300mU/L)，对照组为888(323)mU/L。治疗6周后，服用腐胺蝶呤的患者平均血苯丙氨酸水平下降236mU/L，而安慰剂组的平均血苯丙氨酸水平升高3240mU/L(P<0.05)。
Background Early and strict dietary management of phenylketonuria is the only option to prevent mental retardation. We aimed to test the efficacy of sapropterin, a synthetic form of tetrahydrobiopterin (BH4), for reduction of blood phenylalanine concentration.Methods We enrolled 89 patients with phenylketonuria in a Phase III, multicentre, randomised, double-blind, placebo-controlled trial. We randomly assigned 42 patients to receive oral doses of sapropterin (10 mg/kg) and 47 patients to receive placebo, once daily for 6 weeks. The primary endpoint was mean change from baseline in concentration of phenylalanine in blood after 6 weeks. Analysis was on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT00104247.Findings 88 of 89 enrolled patients received at least one dose of study drug, and 87 attended the week 6 visit. Mean age was 20 (SD 9.7) years. At baseline, mean concentration of phenylalanine in blood was 843 (300) mu mol/L in patients assigned to receive sapropterin, and 888 (323) mu mol/L in controls. After 6 weeks of treatment, patients given sapropterin had a decrease in mean blood phenylalanine of 236 (257) mu mol/L, compared with a 3 (240) mu mol/L increase in the placebo group (p