PREA, PK And Safety PASS Study Of IV Pantoprazole In Pediatric Subjects

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

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.

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 1.
• Use of H2RAs, sucralfate, misoprostol, or prokinetic agents, and bismuth preparations within 1 day (24 hours) before investigational product dosing on Day 1.
• Any disorder requiring chronic (every day) use of warfarin, carbamazepine, or phenytoin, methotrexate, atazanavir or nelfinavir, clopidogrel, and potent inhibitors and inducers of CYP2C19.
• 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.