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首页> 外文期刊>Orphanet journal of rare diseases >Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4?years: results from the SPARK open-label, multicentre, randomized phase IIIb trial
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Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4?years: results from the SPARK open-label, multicentre, randomized phase IIIb trial

机译：<4？年的PKU患者中沙丙蝶呤的功效，安全性和群体药代动力学：SPARK开放标签，多中心，随机IIIb期试验的结果

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BackgroundSapropterin dihydrochloride, a synthetic formulation of BH4, the cofactor for phenylalanine hydroxylase (PAH, EC 1.14.16.1), was initially approved in Europe only for patients ≥4?years with BH4-responsive phenylketonuria. The aim of the SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan?) trial was to assess the efficacy (improvement in daily phenylalanine tolerance, neuromotor development and growth parameters), safety and pharmacokinetics of sapropterin dihydrochloride in children ResultsIn total, 109 male or female children 4-responsive phenylketonuria or mild hyperphenylalaninemia and good adherence to dietary treatment were screened. 56 patients were randomly assigned (1:1) to 10?mg/kg/day oral sapropterin plus a phenylalanine-restricted diet or to only a phenylalanine-restricted diet for 26?weeks (27 to the sapropterin and diet group and 29 to the diet-only group; intention-to-treat population). Of these, 52 patients with ≥1 pharmacokinetic sample were included in the pharmacokinetic analysis, and 54 patients were included in the safety analysis. At week 26 in the sapropterin plus diet group, mean phenylalanine tolerance was 30.5 (95% confidence interval 18.7–42.3) mg/kg/day higher than in the diet-only group ( p ConclusionsThe addition of sapropterin to a phenylalanine-restricted diet was well tolerated and led to a significant improvement in phenylalanine tolerance in children 4-responsive phenylketonuria or mild hyperphenylalaninemia. The pharmacokinetic model favours once per day dosing with adjustment for weight. Based on the SPARK trial results, sapropterin has received EU approval to treat patients 4-responsive phenylketonuria. Trial registrationClinicalTrials.gov, NCT01376908 . Registered June 17, 2011.
机译：背景盐酸沙丙蝶呤是BH 4 的合成配方，苯丙氨酸羟化酶的辅助因子（PAH，EC 1.14.16.1）在欧洲最初仅获批准用于BH 4 < / sub-反应性苯丙酮尿症。 SPARK（安全性小儿药动力学与Kuvan？）试验的目的是评估儿童中盐酸沙丙蝶呤的有效性（每日苯丙氨酸耐受性，神经运动发育和生长参数的改善），安全性和药代动力学结果总共有109名男女儿童筛选出4 反应性苯丙酮尿症或轻度高苯丙氨酸血症，并坚持饮食治疗。 56例患者被随机分配（1：1），以10？mg / kg / day口服沙丙蝶呤加苯丙氨酸限制饮食或仅苯丙氨酸限制饮食26周（其中27分配给沙丙蝶呤和饮食，29分配给苯丙氨酸）。仅饮食人群;意向性治疗人群）。其中，药代动力学分析包括52例≥1药代动力学患者，安全性分析包括54例患者。在第26周时，与仅使用饮食的组相比，在仅使用饮食的组中，苯丙氨酸耐受组的平均苯丙氨酸耐受性高30.5（95％置信区间为18.7–42.3）mg / kg /天（p结论结论良好的耐受性并导致儿童4 -反应性苯丙酮尿症或轻度高苯丙氨酸血症的苯丙氨酸耐受性显着改善，其药代动力学模型有利于每天一次剂量并调整体重。根据SPARK试验结果，沙丙蝶呤已获得欧盟批准用于治疗患者4 反应性苯丙酮尿症。试验注册ClinicalTrials.gov，NCT01376908。2011年6月17日注册。

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