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

Gastroesophageal Reflux Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02401035
• Other study ID #: B1791089
• Secondary ID: 2014-002182-29B1
• Status: Terminated
• Phase: Phase 4
• Start date: May 9, 2017
• Est. completion date: June 18, 2021

Study information

• Verified date: March 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 19
• Est. completion date: June 18, 2021
• Est. primary completion date: June 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease

Intervention

Drug:
• IV pantoprazole
Patients will receive 10 mg, 20 mg, or 40 mg IV pantoprazole determined by weight

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Bosnia and Herzegovina,  Georgia,  Germany,  Italy,  Serbia,  Slovakia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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
Secondary	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

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