Clinical trial NCT02401035: PREA, PK And Safety PASS Study Of IV Pantoprazole In Pediatric Subjects
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Gastroesophageal Reflux Disease
Keywords: candidate for acid suppression therapy
presumptive diagnosis of GERD
clinical diagnosis of suspected GERD
symptomatic GERD
endoscopically proven GERD
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-03-27
Enrollment: 19
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clearance (CL) of Pantoprazole
timeFrame: 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
measure: Volume of Distribution (Vd) of Pantoprazole
timeFrame: 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 outcomes:
measure: Maximum Plasma Concentration (Cmax) of Pantoprazole: Single Dose
timeFrame: 0.25, 1, 2, 3 to 4, and 5 to 6 hours post-dose on Day 1
measure: Cmax of Pantoprazole: Multiple Dose
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero to 24 Hour (AUC24) of Pantoprazole: Single Dose
timeFrame: 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)
measure: Area Under the Plasma Concentration-time Profile From Time Zero to 24 Hour (AUC24) of Pantoprazole: Multiple Dose
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Pantoprazole: Single Dose
timeFrame: 0.25, 1, 2, 3 to 4, and 5 to 6 hours post-dose on Day 1
measure: Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Pantoprazole: Multiple Dose
timeFrame: 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
measure: Terminal Half-Life (t1/2) of Pantoprazole
timeFrame: 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
measure: Number of Participants According to CYP2C19 Genotyping
timeFrame: Day 1
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From Day 1 up to 34 days after the last dose (maximum up to 41 days)
measure: Number of Participants With Laboratory Abnormalities of Potential Clinical Concern
timeFrame: Up to Day 9
measure: Number of Participants With Physical Examination Abnormalities of Potential Clinical Concern
timeFrame: At screening (Day 0)
measure: Number of Participants With Blood Pressure Abnormalities of Potential Clinical Concern
timeFrame: Up to Day 9
measure: Number of Participants With Pulse Rate Abnormalities of Potential Clinical Concern
timeFrame: Up to Day 9
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Children's Health Specialty Center Dallas Campus
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Caba
country: Argentina
facility: Hospital Militar Central "Cirujano Mayor Dr. Cosme Argerich"
state: Buenos Aires
city: Banja Luka
country: Bosnia and Herzegovina
facility: University clinical center of the Republic of Srpska
city: Tbilisi
country: Georgia
facility: JSC Evex Medical Corporation
city: Tbilisi
country: Georgia
facility: LTD Imedi Clinic
city: Bochum
country: Germany
facility: Katholisches Klinikum Bochum
city: Bochum
country: Germany
facility: Zentralapotheke St. Josef-Hospital
city: Roma
country: Italy
facility: Centro Trials - Dipartimento Pediatrico Universitario Ospedaliero Padiglione Salviati
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
city: Roma
country: Italy
facility: IRCCS-Ospedale Pediatrico Bambino Gesù Farmacia Ospedaliera
city: Belgrade
country: Serbia
facility: University Children's Clinic
city: Novi Sad
country: Serbia
facility: Institute for Child and Youth Health Care of Vojvodina
city: Bratislava
country: Slovakia
facility: Narodny ustav detskych chorob
city: Martin
country: Slovakia
facility: Univerzitna nemocnica Martin
city: Dnipro
country: Ukraine
facility: Komunalne pidpryiemstvo Dnipropetrovskyi spetsializovanyi klinichnyi medychnyi tsentr materi
city: Ivano-Frankivsk
country: Ukraine
facility: Komunalne nekomertsiine pidpryiemstvo Ivano-Frankivska oblasna dytiacha klinichna likarnia
city: M. Kherson
country: Ukraine
facility: Komunalne nekomertsiine pidpryiemstvo "Khersonska dytiacha oblasna klinichna likarnia"
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: