B1791089

Principal Investigator: Molly  O'Gorman
Keywords: Acid Suppression , Pantoprazole Department: Pediatric Administration
IRB Number: 00080754 Co Investigator:  
Specialty: Pediatric Gastroenterology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Rebbecca Hanshew
Rebbecca.Perez@hsc.utah.edu
801-213-9105

Brief Summary

Pantoprazole sodium is a proton pump inhibitor indicated in adults and pediatric patients of 12 years of age and above (5 years of age and above in the US) as oral treatment for the healing and symptomatic relief of erosive esophagitis. Pantoprazole sodium is also indicated as oral treatment for maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gastroesophageal reflux disease (GERD). Pantoprazole sodium is further indicated as long-term oral treatment of pathological hypersecretory conditions in adult patients, including Zollinger-Ellison syndrome. The Pantoprazole sodium intravenous (IV) formulation is indicated for short-term treatment (7 to 10 indicated for use in children. Pantoprazole sodium is approved for marketing in more than 90 countries and registered clinical indications vary among countries.

The rationale for conducting this post authorization safety study (PASS) is; to characterize the pharmacokinetic (PK) profile of pantoprazole, following single and repeated once daily IV doses of Pantoprazole sodium in hospitalized pediatric subjects in age group of 1 to 16 years who in the judgment of the investigator are candidates for acid suppression therapy.  These data will address the FDA Post Marketing Requirement (PMRs 145-1 and 255-6).

 
   

OBJECTIVES AND ENDPOINTS

In hospitalized pediatric subjects, age 1 to 16 years who in the judgment of the investigator are candidates for gastric acid suppression therapy, the following are the objectives of this trial:

Primary Objectives

  • To characterize the PK profile of  pantoprazole, following single and repeated once daily IV doses of pantoprazole sodium in pediatric subjects aged 1 to less than 2 years old.
  • To characterize the PK profile of pantoprazole, following single and repeated once daily IV doses of pantoprazole sodium in pediatric subjects aged 2 to 16 years old.

Secondary Objectives

  • To determine the safety and tolerability of single and multiple once daily doses of IV pantoprazole sodium in each of the two independent age cohorts over 7 days.
  • 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.

Inclusion Criteria

Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

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. Hospitalized subjects 1 to 16 years who in the judgment of the investigator are candidates for acid suppression therapy (ie, those with a presumptive diagnosis of GERD, a clinical diagnosis of suspected GERD, symptomatic GERD, or endoscopically proven GERD).

​- Please note that PACL dated 15Dec2016 includes the following clarification:

“In… toddlers, there is no symptom or symptom complex that is diagnostic of GERD or predicts response.”1  Therefore it would be expected that younger children who are enrolled in this study would have had an objective diagnosis of GERD, as described in the American Academy of Pediatrics’ Gastroesophageal Reflux Management Guidance for the Pediatrician. “Diagnostic tests must be used in a thoughtful and serial manner to document the presence of reflux of gastric contents in the esophagus, to detect complications, to establish a causal relationship between reflux and symptoms, to evaluate the efficacy of therapies, and to exclude other conditions. The diagnostic methods most commonly used to evaluate pediatric patients with GERD symptoms are upper gastrointestinal (GI) tract contrast radiography, esophageal pH and/or impedance monitoring, and upper endoscopy with esophageal biopsy.”2    These or other medically appropriate, objective methods should be employed in young children for whom symptoms would not be diagnostic

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 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.
 
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. Male and female subjects of childbearing potential (those have started their period and are sexually active - interview will be conducted at the screening visit to determine 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 (those have started their period and are sexually active - interview will be conducted at the screening visit to determine 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.

Exclusion Criteria

Exclusion Criteria
Subjects presenting with any of the following will not be included in the study:
 
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) (Phases 1-4) or treatment with an investigational drug within 30 days or 5 half-lives before the first
dose of the investigational product 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; males and females of childbearing potential (those have started their period and are sexually active - interview will be conducted at the screening visit to determine 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. History or presence of upper gastrointestinal anatomic or motor disorders, including the following:
a. Esophageal strictures, webs, or diverticulae.
b. Gastrointestinal strictures of any kind.
c. Esophageal or gastric motor disorders (eg, scleroderma).
d. Barrett’s esophagus.
e. Peptic ulcer disease, erosive gastritis and/or erosive duodenitis.
f. Known eosinophilic esophagitis by histology.
g. Gastrointestinal malabsorption.
h. Known active Helicobacter pylori infection.
 
8. Known hypersensitivity to proton pump inhibitors (PPIs), including pantoprazole or to any substituted benzimidazole or to any of the excipients.
 
9. History of treatment with any PPI (eg, omeprazole, esomeprazole, lansoprazole, rabeprazole, or pantoprazole) within 2 weeks (14 days) before Day 1.
 
10. 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 2 weeks (14 days) before Day 1.
 
11. Any disorder requiring chronic (every day) use of warfarin, carbamazepine, or phenytoin, methotrexate, atazanavir or nelfinavir, clopidogrel, and potent inhibitors
and inducers of CYP2C19.
 
12. Chronic (daily) use of glucocorticoids (eg, prednisone, prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
 
13. 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).
 
14. Diagnosed as having or has received treatment for esophageal, gastric, pyloric channel, or duodenal ulceration within 30 days before Screening.

15. 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.

16. 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.
 
17. History of sensitivity to heparin or heparin-induced thrombocytopenia.