AN OPEN-LABEL, MULTICENTER STUDY TO EVALUATE THE PHARMACOKINETICS OF SINGLE AND MULTIPLE INTRAVENOUS DOSES OF PANTOPRAZOLE IN TWO AGE COHORTS OF HOSPITALIZED PEDIATRIC SUBJECTS 1 TO 16 YEARS OF AGE WHO ARE CANDIDATES FOR ACID SUPPRESSION THERAPY
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 19
- 试验地点
- 19
- 主要终点
- Clearance (CL) of Pantoprazole
研究概览
简要总结
The purpose of this study is to characterize the pharmacokinetics (PK) and safety of intravenous (IV) pantoprazole in patients 1 to 16 years old who are candidates for acid suppression therapy.
详细描述
In hospitalized pediatric subjects, age 1 to 16 years who in the judgment of the investigator are candidates for acid suppression therapy, the following are the objectives of this trial:
Primary Objectives To characterize the PK of single and multiple IV doses of pantoprazole in pediatric subjects aged 1 to less than 2 years old.
To characterize the PK of single and multiple IV doses of pantoprazole in pediatric subjects aged 2 to 16 years old.
Secondary Objectives To determine the safety, tolerability, and PK of single and multiple IV doses of pantoprazole in each of the independent age cohorts.
To assess the CYP2C19 genotype in pediatric subjects receiving IV pantoprazole, to determine the presence of the gene for the major enzyme responsible for metabolism of pantoprazole.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects aged 1 to 16 years who in the judgment of the investigator are candidates for gastric acid suppression therapy (ie, those with a presumptive diagnosis of GERD, a clinical diagnosis of suspected GERD, symptomatic GERD, or endoscopically proven GERD) and whom the investigator judges would need to receive IV PPI therapy for at least 4 days.
- •Body weight > 5th percentile for age.
- •Y-site or dedicated IV line for administration of pantoprazole sodium.
- •Expected survival for at least 30 days.
- •Fertile male and female subjects of childbearing potential at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. Female subjects of non-childbearing potential must be premenarchal, have undergone hysterectomy with bilateral oophorectomy, have medically confirmed ovarian failure, or achieved post-menopausal status.
排除标准
- •Participation in other studies involving investigational drug(s) or treatment with an investigational drug within 30 days or 5 half lives prior to study entry and/or during study participation.
- •Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
- •Pregnant females; breastfeeding females; fertile male subjects, and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception for the duration of the study and for at least 28 days after last dose of investigational product.
- •Serum CK levels >3x ULN.
- •Known history of HIV or clinical manifestations of AIDS.
- •Known hypersensitivity to PPIs or to any substituted benzimidazole or to any of the excipients.
- •History of treatment with any PPI within 2 days (48 hours) before investigational product dosing on Day
- •Use of H2RAs, sucralfate, misoprostol, or prokinetic agents, and bismuth preparations within 1 day (24 hours) before investigational product dosing on Day
- •Any disorder requiring chronic (every day) use of warfarin, carbamazepine, or phenytoin, methotrexate, atazanavir or nelfinavir, clopidogrel, and potent inhibitors and inducers of CYP2C
- •Chronic (daily) use of glucocorticoids. Steroid inhalers and topical steroids may be used.
- •Active malignancy of any type, or history of a malignancy (Subject with a history of malignancies that have been surgically removed or eradicated by irradiation or chemotherapy and who have no evidence of recurrence for at least 5 years before Screening are acceptable).
- •ALT or BUN >2.0 ULN or estimated creatinine >1.5 X ULN for age or any other laboratory abnormality considered by the Investigator to be clinically significant within 14 days before Screening.
- •In the Investigator's opinion, a chronic condition (eg, diabetes, epilepsy), which is either not stable or well controlled and may interfere with the conduct of the study.
- •History of sensitivity to heparin or heparin induced thrombocytopenia.
研究组 & 干预措施
IV pantoprazole
Patients will receive 10 mg, 20 mg, or 40 mg IV pantoprazole determined by weight.
干预措施: IV pantoprazole (Drug)
结局指标
主要结局
Clearance (CL) of Pantoprazole
时间窗: 0.25, 1 to 2, 3 to 4, and 5 to 6 hours post-dose on Day 1; 0.25, 0.5, 1 to 2, 3 to 4, and 5 to 6, 8, and 12 hours post-dose on Day 2; 0.25, 0.5, 1, 2, 4, 8, and 12 hours post-dose on Day 7
Data reported below is combined for Days 1, 2 and 7.
Volume of Distribution (Vd) of Pantoprazole
时间窗: 0.25, 1 to 2, 3 to 4, and 5 to 6 hours post-dose on Day 1; 0.25, 0.5, 1 to 2, 3 to 4, and 5 to 6, 8, and 12 hours post-dose on Day 2; 0.25, 0.5, 1, 2, 4, 8, and 12 hours post-dose on Day 7
Data reported below is combined for Days 1, 2 and 7.
次要结局
- Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Pantoprazole: Multiple Dose(0.25, 0.5, 1 to 2, 3 to 4, and 5 to 6, 8, and 12 hours post-dose on Day 2; 0.25, 0.5, 1, 2, 4, 8, and 12 hours post dose on Day 7)
- Area Under the Plasma Concentration-time Profile From Time Zero to 24 Hour (AUC24) of Pantoprazole: Multiple Dose(0.25, 0.5, 1 to 2, 3 to 4, and 5 to 6, 8, and 12 hours post-dose on Day 2; 0.25, 0.5, 1, 2, 4, 8, and 12 hours post dose on Day 7)
- Maximum Plasma Concentration (Cmax) of Pantoprazole: Single Dose(0.25, 1, 2, 3 to 4, and 5 to 6 hours post-dose on Day 1)
- Area Under the Plasma Concentration-time Profile From Time Zero to 24 Hour (AUC24) of Pantoprazole: Single Dose(0.25, 1, 2, 3 to 4, and 5 to 6 hours post-dose on Day 1; 24 hours post dose on Day 1 (pre dose on Day 2))
- Terminal Half-Life (t1/2) of Pantoprazole(0.25, 1 to 2, 3 to 4, and 5 to 6 hours post-dose on Day 1; 0.25, 0.5, 1 to 2, 3 to 4, and 5 to 6, 8, and 12 hours post-dose on Day 2; 0.25, 0.5, 1, 2, 4, 8, and 12 hours post-dose on Day 7)
- Number of Participants With Adverse Events (AEs)(From Day 1 up to 34 days after the last dose (maximum up to 41 days))
- Number of Participants With Physical Examination Abnormalities of Potential Clinical Concern(At screening (Day 0))
- Number of Participants With Pulse Rate Abnormalities of Potential Clinical Concern(Up to Day 9)
- Cmax of Pantoprazole: Multiple Dose(0.25, 0.5, 1 to 2, 3 to 4, and 5 to 6, 8, and 12 hours post-dose on Day 2; 0.25, 0.5, 1, 2, 4, 8, and 12 hours post dose on Day 7)
- Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Pantoprazole: Single Dose(0.25, 1, 2, 3 to 4, and 5 to 6 hours post-dose on Day 1)
- Number of Participants According to CYP2C19 Genotyping(Day 1)
- Number of Participants With Laboratory Abnormalities of Potential Clinical Concern(Up to Day 9)
- Number of Participants With Blood Pressure Abnormalities of Potential Clinical Concern(Up to Day 9)