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.

Study Overview

• Status: Terminated
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: IV pantoprazole

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1426BOS
      • Hospital Militar Central "Cirujano Mayor Dr. Cosme Argerich"
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Center of the Republic of Srpska
• Georgia
  • Tbilisi, Georgia, 0159
    • JSC Evex Medical Corporation
  • Tbilisi, Georgia, 0159
    • LTD Imedi Clinic
• Germany
  • Bochum, Germany, 44791
    • Katholisches Klinikum Bochum
  • Bochum, Germany, 44791
    • Zentralapotheke St. Josef-Hospital
• Italy
  • Roma, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu
  • Roma, Italy, 00165
    • Centro Trials - Dipartimento Pediatrico Universitario Ospedaliero Padiglione Salviati
  • Roma, Italy, 00165
    • IRCCS-Ospedale Pediatrico Bambino Gesù Farmacia Ospedaliera
• Serbia
  • Belgrade, Serbia, 11000
    • University Children's Clinic
  • Novi Sad, Serbia, 21000
    • Institute for Child and Youth Health Care of Vojvodina
• Slovakia
  • Bratislava, Slovakia, 833 40
    • Narodny ustav detskych chorob
  • Martin, Slovakia, 036 59
    • Univerzitná nemocnica Martin
• Ukraine
  • Dnipro, Ukraine, 49006
    • Komunalne pidpryiemstvo Dnipropetrovskyi spetsializovanyi klinichnyi medychnyi tsentr materi
  • Ivano-Frankivsk, Ukraine, 76018
    • Komunalne nekomertsiine pidpryiemstvo Ivano-Frankivska oblasna dytiacha klinichna likarnia
  • M. Kherson, Ukraine, 73013
    • Komunalne nekomertsiine pidpryiemstvo "Khersonska dytiacha oblasna klinichna likarnia"
• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center Dallas
    • Dallas, Texas, United States, 75207
      • Children's Health Specialty Center Dallas Campus
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV pantoprazole; Patients will receive 10 mg, 20 mg, or 40 mg IV pantoprazole determined by weight.	Drug: IV pantoprazole; Patients will receive 10 mg, 20 mg, or 40 mg IV pantoprazole determined by weight

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance (CL) of Pantoprazole	Data reported below is combined for Days 1, 2 and 7.	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
Volume of Distribution (Vd) of Pantoprazole	Data reported below is combined for Days 1, 2 and 7.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Pantoprazole: Single Dose	The results for Cmax were presented separately for single dose and multiple doses.	0.25, 1, 2, 3 to 4, and 5 to 6 hours post-dose on Day 1
Cmax of Pantoprazole: Multiple Dose	Data reported below is combined for Days 2 and 7.	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: Single Dose	The results for AUC24 were presented separately for single dose and multiple doses.	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)
Area Under the Plasma Concentration-time Profile From Time Zero to 24 Hour (AUC24) of Pantoprazole: Multiple Dose	Data reported below is combined for Days 2 and 7.	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	The results for AUCinf were presented separately for single dose and multiple doses.	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 Extrapolated to Infinite Time (AUCinf) of Pantoprazole: Multiple Dose	Data reported below is combined for Days 2 and 7.	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
Terminal Half-Life (t1/2) of Pantoprazole	Data reported below is combined for Days 1, 2 and 7.	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 According to CYP2C19 Genotyping	CYP2C19 genotype was assessed in pediatric participants who received intravenous pantoprazole sodium and determined the presence of the gene for the major enzyme responsible for metabolism of pantoprazole.	Day 1
Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a product; the event need not necessarily had a causal relationship with the treatment or usage.	From Day 1 up to 34 days after the last dose (maximum up to 41 days)
Number of Participants With Laboratory Abnormalities of Potential Clinical Concern	Number of participants with abnormalities in laboratory parameters of potential clinical concern were reported in this outcome measure. The criteria to determine the abnormalities was determined by the investigator.	Up to Day 9
Number of Participants With Physical Examination Abnormalities of Potential Clinical Concern	Number of participants with abnormalities in physical examination of potential concern were reported in this outcome measure. The criteria to determine the abnormalities was determined by the investigator.	At screening (Day 0)
Number of Participants With Blood Pressure Abnormalities of Potential Clinical Concern	Number of participants with abnormalities in blood pressure of potential clinical concern were reported in this outcome measure. The criteria to determine the abnormalities was determined by the investigator.	Up to Day 9
Number of Participants With Pulse Rate Abnormalities of Potential Clinical Concern	Number of participants with abnormalities in pulse rate of potential clinical concern were reported in this outcome measure. The criteria to determine the abnormalities was determined by the investigator.	Up to Day 9

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2017
• Primary Completion (Actual): June 18, 2021
• Study Completion (Actual): June 18, 2021

Study Registration Dates

• First Submitted: December 15, 2014
• First Submitted That Met QC Criteria: March 23, 2015
• First Posted (Estimated): March 27, 2015

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: candidate for acid suppression therapy; presumptive diagnosis of GERD; clinical diagnosis of suspected GERD; symptomatic GERD; endoscopically proven GERD
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: B1791089 (Other Identifier: Study Number); 2014-002182-29 (EudraCT Number); GERD (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No