About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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);
Disqualifiers
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.
Trial population
Long term treatment for pediatric patients with UCD, aged 0-18 years, who cannot be managed with protein restriction and/or amino acid supplementation alone, including carbamoyl phosphate synthetase I deficiency, ornithine carbamoyltransferase deficiency, citrullinemia type I, argininosuccinic aciduria, argininemia, and hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome.
Trial design
Cohort
Prospective
Treatments tested in this trial
Glycerol phenylbutyrate Oral Liquid
DrugAdministration and dosage: The recommended total daily dose of glycerol phenylbutyrate is calculated based on the patient's body surface area, ranging from 4.5 mL/m2/d to 11.2 mL/m2/d: 1. Recommended initial dose in phenylbutyrate-naïve patients * Patients with body surface area (BSA) \< 1.3 m2: 8.5 mL/m2/day * Patients with body surface area (BSA) ≥ 1.3 m2: 7 mL/m2/day 2. Initial dose for patients switching from sodium phenylbutyrate to glycerol phenylbutyrate: Total daily dose of glycerol phenylbutyrate (ml) = total daily dose of sodium phenylbutyrate granules (g) ×0.81 Medication Schedule: The daily total dose should be divided into equal amounts and administered with each meal or feeding (such as three to six times daily).
Treatment groups
Trial outcomes
Primary outcomes
Mean blood ammonia levels at month 3 after enrollment.
The average of blood ammonia levels at months 3 after enrollment.
Secondary outcomes
Mean blood ammonia levels
The average of blood ammonia levels at period of baseline, month 1, month 6, and every 6 months thereafter (1-5 years)
Maximum blood ammonia levels
The maximum blood ammonia levels at period of baseline, month 1, month 3, month 6, and every 6 months thereafter (1-5 years)
Frequency of hyperammonaemic crisis
The frequency of hyperammonaemic crisis at period of baseline, month 1, month 3, month 6, and every 6 months thereafter (1-5 years)
Height
The change of height to the baseline in children aged 0-18 years old, and the proportion of weight in the upper, upper-middle, middle, lower-middle, and lower categories for each age group, according to the growth standards for children under 7 years old (WS/T 423-2022) and standard for height level classification among children and adolescents aged 7\~18 years (WS/T 612-2018)issued by the National Health Commission of the People's Republic of China.
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