A study to evaluate the pharmacokinetics (the way the body absorbs, distributes and eliminates the drug) of the study drug pantoprazole in hospitalized children aged 1-16 years old who are candidates for acid suppression therapy.
- Conditions
- Gastroesophageal Reflux Disease (GERD)Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2014-002182-29-DE
- Lead Sponsor
- Pfizer Inc, 235 East 42nd Street, New York, NY 1007
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
1. Evidence of a personally signed and dated informed consent document indicating that the parent/legal guardian has been informed of all pertinent aspects of the study.
2. Evidence of a personally signed and dated assent, indicating that the subject understands the nature of all pertinent aspects of the study, and is willing to participate in the study activities, if applicable, as consistent with the subject’s age and ability to provide assent.
3. The subject (to degree appropriate for age) and parent or legal guardian are able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and are likely to complete the study as planned.
4. 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.
5. Physical examination and clinical laboratory evaluations within normal limits unless the investigator documents that the deviations are not clinically significant or are directly related to the reason for gastric acid suppression therapy or to the subject’s underlying disease process.
6. Body weight >5th percentile for subject’s age.
7. Y-site or dedicated IV line for administration of pantoprazole sodium.
8. Expected survival for at least 30 days.
9. The subject (to degree appropriate for age) and parent or legal guardian are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
10. Fertile male subjects and female subjects of childbearing potential and 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.
a. If subject is a female of childbearing potential, she must agree to use adequate contraception and must have a negative serum pregnancy test within 24 hours prior to administration of investigational product.
Female subjects of non-childbearing potential must meet at least one of the following criteria:
a. Premenarchal: The investigator (or other appropriate staff) must discuss the subject’s premenarchal status with the subject or parent/caregiver at office visits and during telephone contacts, as subjects who achieve menarche during the study would no longer be considered female subjects of nonchildbearing potential” and must comply with the protocol requirements applicable to women of childbearing potential;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure; or
d. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or
physiological cause; status may be confirmed by having a serum
follicle stimulating hormone (FSH) level confirming the post-menopausal state.
All other female subjects (including females with tubal ligations) will be
considered to be of childbearing potential.
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Participation in other studies involving investigational drug(s) within 30 days or 5 half-lives prior to study entry and/or during study participation.
3. 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.
4. 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 as outlined in this protocol for the duration of the study and for at least 28 days after last dose of investigational product.
5. Serum creatine kinase levels >3x upper limit of normal.
6. Known history of human immunodeficiency virus (HIV) or clinical manifestations of acquired immune deficiency syndrome (AIDS).
7. Known hypersensitivity to proton pump inhibitors (PPIs), including pantoprazole sodium or to any substituted benzimidazole or to any of the excipients.
8. History of treatment with any PPI (eg, omeprazole, esomeprazole, lansoprazole, rabeprazole, or pantoprazole sodium) within 2 days (i.e. 48 hours) before investigational product dosing on Day 1.
9. Use of Histamine 2 Receptor Blockers (H2RAs) (eg, cimetidine, famotidine, ranitidine or nizatidine), sucralfate, misoprostol, or prokinetic agents (eg, cisapride, urecholine, erythromycin or metoclopramide), and bismuth preparations within 1 day (i.e. 24 hours) before investigational product dosing on Day 1, whether prescription or over the counter.
10. Any disorder requiring chronic (every day) use of warfarin, carbamazepine, or phenytoin, methotrexate, atazanavir or nelfinavir, clopidogrel, and potent inhibitors and inducers of CYP2C19.
11. Chronic (daily) use of glucocorticoids (eg, prednisone, prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
12. 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).
13. Alanine aminotransferase (ALT) or Blood urea nitrogen (BUN) >2.0 Upper limit of normal (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.
14. 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.
15. History of sensitivity to heparin or heparin-induced thrombocytopenia.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To characterize the PK of pantoprazole, following single and multiple IV doses of pantoprazole sodium in pediatric subjects aged 1 to less than 2 years old.<br><br>To characterize the PK of pantoprazole, following single and multiple IV doses of pantoprazole sodium in pediatric subjects aged 2 to 16 years old.;Secondary Objective: To determine the safety, tolerability and PK of single and multiple IV doses of pantoprazole sodium in each of the two independent age cohorts.<br><br>To assess the CYP2C19 genotype in pediatric subjects receiving IV pantoprazole sodium, to determine the presence of the gene for the major enzyme responsible for metabolism of pantoprazole.;Primary end point(s): PK Parameters: clearance (CL) and volume of distribution (Vd).;Timepoint(s) of evaluation of this end point: Day 1 and Day 2.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): PK Parameters to be estimated from the population PK model:<br>Maximum plasma concentration (Cmax), area under the plasma concentration-time profile from time zero to the 24 hour time post dose (AUC24), area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUCinf) and terminal phase half-life (T1/2) of pantoprazole following single and multiple IV doses.<br><br>1. Safety and tolerability of single- and multiple doses of IV pantoprazole sodium for each of the two age cohorts will be assessed by physical examinations, adverse event (AE) monitoring, clinical laboratory measurements, blood pressure, and pulse rate.<br><br>2. CYP2C19 genotype to determine the presence of the gene for the major enzyme responsible for metabolism of pantoprazole.;Timepoint(s) of evaluation of this end point: 1. Throughout the trial. <br><br>2. Samples for CYP2C19 genotype analysis will be collected pre-dose.