A Single-arm, Prospective, Multi-center Post-market Clinical Study of Glycerol Phenylbutyrate in Chinese Patients With Urea Cycle Disorders
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 7
- 主要终点
- Mean blood ammonia levels at month 3 after enrollment.
研究概览
简要总结
Urea cycle disorders (UCD) are rare diseases in China, would lead to high mortality and disability, which require long-term management due to the recurrent symptoms. This multi-center, prospective, single-arm study was designed to assess the efficacy and safety of Glycerol Phenylbutyrate for Chinese pediatric patients with UCD, to provide the additional references and treatment options for Chinese UCD patients, and enhance the clinical management of UCD in China. This study primarily observes patients with UCD who are on long-term treatment with glyceryl phenylbutyrate, the total planned observation period is 5 years.
详细描述
The duration of treatment with GPB in this study was 5 years. Forty participants aged 0-18 years with a diagnosis of UCD, including carbamoyl phosphate synthetase I deficiency, ornithine carbamoyltransferase deficiency, citrullinemia type I, argininosuccinic aciduria, argininemia, or hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, and who plan to use and have not used glycerol phenylbutyrate in the previous 3 months (including 3 months) were enrolled. Participants should return to clinic visits at 1 month and 3 months after enrollment. They were queried about any adverse events (AEs), dosage change of the study drug or hyperammonemic crises (HACs) that occurred since the last visit, and blood samples were collected for the analysis of ammonia and blood biochemistry. Then the detailed information on AEs, dosage change of the study drug, HACs, and data about ammonia, routine clinical laboratory safety tests and neurocognitive outcomes that have been actually completed in the clinical practice of the patients will be collected every 6 months until 5 years. Height, weight and/or head circumference data were also collected at each visit. The assessments would be conducted at 1, 3, and 6 months, and subsequently on a semi-annual basis. The evaluation of ammonia levels, frequency of HACs, dosage of the study drug, AEs, serious AEs, and concomitant medications were included. The neurocognitive outcomes, growth and development of the participants would be described at the end.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 0 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 0-18 years;
- •Subject and/or subject's legally authorized representative willing to follow the therapeutic regimen, dietary management and visit plan of the study, and voluntarily signing informed consent form;
- •Patients with the following subtypes of UCD: Carbamoyl phosphate synthetase I deficiency, Ornithine translocase deficiency, citrullinemia type I, argininosuccinic aciduria, argininemia, and hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome;
- •Patients planned to use glycerol phenylbutyrate who have not used it in past 3 months (including at the time of 3 months);
- •Men with fertility and women of childbearing potential (with menstruation) who are willing to take effective contraceptive measures during the period from the date of signing the informed consent to 1 months after the last dose of the study drug, such as abstinence, condoms, intra-uterine contraceptive devices, and double barrier methods (such as condoms + contraceptive diaphragms). Pregnancy test results must be negative for women of childbearing age within ≤ 7 days before the initial administration of study drug.
排除标准
- •Hypersensitivity to any of the active ingredient, including phenylbutyrate (PBA), phenylacetate acid (PAA) and phenylacetyl glutamine (PAGN), or excipients;
- •Use of any drug known to significantly affect renal clearance (such as probenecid) or increase protein catabolism (such as corticosteroids) or other drugs known to increase blood ammonia levels (such as valproate) within 24 h before the first administration;
- •Use of other nitrogen-scavenging agent at the same time after enrollment, such as sodium phenylbutyrate and sodium benzoate;
- •Pregnant or breastfeeding females.
- •Other reasons, in the opinion of the investigator, that may affect the patient's compliance and safety in participating in the study.
研究组 & 干预措施
Glycerol phenylbutyrate cohort
Glycerol Phenylbutyrate was used.
干预措施: Glycerol phenylbutyrate Oral Liquid (Drug)
结局指标
主要结局
Mean blood ammonia levels at month 3 after enrollment.
时间窗: months 3
The average of blood ammonia levels at months 3 after enrollment.
次要结局
- Mean blood ammonia levels(Baseline, Month 1, Month 6, and every 6 months thereafter (1-5 years))
- Maximum blood ammonia levels(Baseline, Month 1, Month 3, Month 6, and every 6 months thereafter (1-5 years))
- Frequency of hyperammonaemic crisis(Baseline, Month 1, Month 3, Month 6, and every 6 months thereafter (1-5 years))
- Height(Baseline, Month 1, Month 3, Month 6, and every 6 months thereafter (1-5 years).)
- Weight(Baseline, Month 1, Month 3, Month 6, and every 6 months thereafter (1-5 years))
- Head circumference(Baseline, Month 1, Month 3, Month 6, and every 6 months thereafter (1-5 years))
- Dose adjustment changes(Baseline, Month 1, Month 3, Month 6, and every 6 months thereafter (1-5 years))
- Mean Neonatal Behavioral Neurological Assessment Scores: Behavioral ability, passive muscle tone, active muscle tone, primitive reflexes, and general assessment(Month 6, every year thereafter (1-5 years))
- Mean Bayley Scale of Infant Development Scores: mental scale, motor scale(Month 6, every year thereafter (1-5 years))
- Mean Gesell Developmental Diagnosis Scale Scores(Month 6, every year thereafter (1-5 years))
- Mean Wechsler Preschool and Primary Scale of Intelligence Scores: The Verbal Intelligence Quotient, the Performance Intelligence Quotient(Month 6, every year thereafter (1-5 years))
- Mean Wechsler Intelligence Scale for Children Scores: The Verbal Intelligence Quotient, the Performance Intelligence Quotient(Month 6, every year thereafter (1-5 years))